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FDA approves triple drug combo for melanoma
The US Food and Drug Administration (FDA) has approved the triple-therapy combination of atezolizumab (Tecentriq) plus cobimetinib (Cotellic) and vemurafenib (Zelboraf) for the treatment of BRAF V600 mutation-positive advanced melanoma, according to a press statement from Genentech, which owns all three drugs.
This is the first melanoma indication for the PD-L1 inhibitor atezolizumab; the other two drugs, cobimetinib and vemurafenib, are a MEK- plus BRAF-inhibitor combination previously approved for BRAF-mutated melanoma.
The new approval is based on safety and efficacy results from the randomized, phase 3 IMspire150 study from patients with previously untreated BRAF V600 mutation-positive metastatic or unresectable locally advanced melanoma.
Progression-free survival (PFS), the primary endpoint, was improved by 4.5 months with the triple therapy compared to the doublet.
The addition of atezolizumab to cobimetinib and vemurafenib led to a longer median PFS of 15.1 months, compared to 10.6 months with placebo plus cobimetinib and vemurafenib (hazard ratio, 0.78; 95% CI, 0.63 – 0.97; P = .025).
The most common adverse reactions (rate ≥ 20%) in patients who received the triple combination were rash (75%), musculoskeletal pain (62%), fatigue (51%), hepatotoxicity (50%), pyrexia (49%), nausea (30%), pruritus (26%), edema (26%), stomatitis (23%), hypothyroidism (22%), and photosensitivity reaction (21%).
The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that facilitates concurrent submission and review of oncology products among international partners.
This article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved the triple-therapy combination of atezolizumab (Tecentriq) plus cobimetinib (Cotellic) and vemurafenib (Zelboraf) for the treatment of BRAF V600 mutation-positive advanced melanoma, according to a press statement from Genentech, which owns all three drugs.
This is the first melanoma indication for the PD-L1 inhibitor atezolizumab; the other two drugs, cobimetinib and vemurafenib, are a MEK- plus BRAF-inhibitor combination previously approved for BRAF-mutated melanoma.
The new approval is based on safety and efficacy results from the randomized, phase 3 IMspire150 study from patients with previously untreated BRAF V600 mutation-positive metastatic or unresectable locally advanced melanoma.
Progression-free survival (PFS), the primary endpoint, was improved by 4.5 months with the triple therapy compared to the doublet.
The addition of atezolizumab to cobimetinib and vemurafenib led to a longer median PFS of 15.1 months, compared to 10.6 months with placebo plus cobimetinib and vemurafenib (hazard ratio, 0.78; 95% CI, 0.63 – 0.97; P = .025).
The most common adverse reactions (rate ≥ 20%) in patients who received the triple combination were rash (75%), musculoskeletal pain (62%), fatigue (51%), hepatotoxicity (50%), pyrexia (49%), nausea (30%), pruritus (26%), edema (26%), stomatitis (23%), hypothyroidism (22%), and photosensitivity reaction (21%).
The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that facilitates concurrent submission and review of oncology products among international partners.
This article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved the triple-therapy combination of atezolizumab (Tecentriq) plus cobimetinib (Cotellic) and vemurafenib (Zelboraf) for the treatment of BRAF V600 mutation-positive advanced melanoma, according to a press statement from Genentech, which owns all three drugs.
This is the first melanoma indication for the PD-L1 inhibitor atezolizumab; the other two drugs, cobimetinib and vemurafenib, are a MEK- plus BRAF-inhibitor combination previously approved for BRAF-mutated melanoma.
The new approval is based on safety and efficacy results from the randomized, phase 3 IMspire150 study from patients with previously untreated BRAF V600 mutation-positive metastatic or unresectable locally advanced melanoma.
Progression-free survival (PFS), the primary endpoint, was improved by 4.5 months with the triple therapy compared to the doublet.
The addition of atezolizumab to cobimetinib and vemurafenib led to a longer median PFS of 15.1 months, compared to 10.6 months with placebo plus cobimetinib and vemurafenib (hazard ratio, 0.78; 95% CI, 0.63 – 0.97; P = .025).
The most common adverse reactions (rate ≥ 20%) in patients who received the triple combination were rash (75%), musculoskeletal pain (62%), fatigue (51%), hepatotoxicity (50%), pyrexia (49%), nausea (30%), pruritus (26%), edema (26%), stomatitis (23%), hypothyroidism (22%), and photosensitivity reaction (21%).
The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that facilitates concurrent submission and review of oncology products among international partners.
This article first appeared on Medscape.com.
EMA gives green light to avapritinib for GIST, acalabrutinib for CLL
The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.
The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.
The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.
Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.
First targeted therapy for mutation
If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.
Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.
For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.
“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.
The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.
In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website.
Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.
New treatment for CLL
Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year. In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.
The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.
In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).
At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).
The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.
In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).
At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).
The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
A version of this article first appeared on Medscape.com.
The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.
The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.
The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.
Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.
First targeted therapy for mutation
If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.
Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.
For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.
“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.
The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.
In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website.
Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.
New treatment for CLL
Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year. In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.
The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.
In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).
At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).
The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.
In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).
At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).
The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
A version of this article first appeared on Medscape.com.
The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.
The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.
The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.
Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.
First targeted therapy for mutation
If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.
Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.
For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.
“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.
The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.
In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website.
Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.
New treatment for CLL
Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year. In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.
The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.
In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).
At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).
The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.
In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).
At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).
The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
A version of this article first appeared on Medscape.com.
FDA okays new CAR T therapy, first for mantle cell lymphoma
The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.
“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”
In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”
The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).
In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response.
Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.
In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.
Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.
“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”
In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”
The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).
In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response.
Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.
In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.
Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.
“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”
In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”
The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).
In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response.
Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.
In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.
Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.
A version of this article originally appeared on Medscape.com.
One-third of outpatients with COVID-19 are unwell weeks later
, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.
Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.
Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.
Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.
Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.
The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.
Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.
Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.
Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.
“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.
Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.
“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.
Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.
“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.
The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
A version of this article originally appeared on Medscape.com.
, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.
Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.
Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.
Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.
Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.
The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.
Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.
Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.
Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.
“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.
Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.
“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.
Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.
“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.
The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
A version of this article originally appeared on Medscape.com.
, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.
Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.
Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.
Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.
Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.
The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.
Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.
Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.
Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.
“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.
Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.
“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.
Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.
“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.
The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
A version of this article originally appeared on Medscape.com.
New CDC guidance for health care personnel exposed to HCV
The new guidance was developed in part as a result of an increase in the incidence of acute HCV infection in the United States, which increases the risk for occupational exposure among HCP. “[I]n certain health care settings, HCP might be exposed to source patients with early HCV infection before those patients develop serologic evidence of infection or symptoms indicative of viral hepatitis,” wrote the authors of the report, published online July 24 in the CDC’s Morbidity and Mortality Weekly Report.
The guidelines, which no longer recommend waiting for spontaneous resolution upon initial diagnosis, include recommendations and algorithms for baseline and follow-up testing, appropriate test type, and recommendations for clinical management. The recommendations were developed on the basis of a current literature review, expert opinion from subject matter experts, and recent guidance from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.
Baseline testing ASAP
Baseline testing of the source patient and the HCP should be performed as soon as possible, preferably within 48 hours of exposure. The source patient should be tested for HCV RNA using a nucleic acid test. Alternatively, screening anti-HCV serology can be performed in patients at low risk for HCV and a nucleic acid test performed if serology is positive.
Baseline testing for the HCP should include anti-HCV testing and, if positive, HCV RNA testing is recommended. HCPs who test positive for HCV RNA at baseline are considered to have a preexisting HCV infection and should be referred for treatment.
Follow-up testing
For HCPs with exposure to blood or body fluids from a patient who is anti-HCV positive but HCV RNA negative, follow-up testing is not required.
If the source patient is HCV RNA positive, or if status of the source patient is unknown, the authors recommend that exposed HCPs have HCV RNA follow-up testing at 3-6 weeks post exposure, in addition to baseline testing. A final anti-HCV test is recommended at 4-6 months post exposure as there can be potential periods of aviremia during acute HCV infection.
Exposed HCPs who develop signs of illness indicative of HCV infection at any time should be tested for HCV RNA.
HCPs with positive HCV RNA test results should be referred for care and curative antiviral therapy.
Postexposure prophylaxis is not recommended
Recent data have shown that the risk for HCV infection from percutaneous exposure is 0.2% and from mucocutaneous exposure is 0%. On the basis of this information, the CDC guidelines no longer recommend routine postexposure prophylaxis for HCPs with occupational exposure to HCV. Rather, curative antiviral regimens should be reserved for instances of documented HCV transmission.
The authors disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The new guidance was developed in part as a result of an increase in the incidence of acute HCV infection in the United States, which increases the risk for occupational exposure among HCP. “[I]n certain health care settings, HCP might be exposed to source patients with early HCV infection before those patients develop serologic evidence of infection or symptoms indicative of viral hepatitis,” wrote the authors of the report, published online July 24 in the CDC’s Morbidity and Mortality Weekly Report.
The guidelines, which no longer recommend waiting for spontaneous resolution upon initial diagnosis, include recommendations and algorithms for baseline and follow-up testing, appropriate test type, and recommendations for clinical management. The recommendations were developed on the basis of a current literature review, expert opinion from subject matter experts, and recent guidance from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.
Baseline testing ASAP
Baseline testing of the source patient and the HCP should be performed as soon as possible, preferably within 48 hours of exposure. The source patient should be tested for HCV RNA using a nucleic acid test. Alternatively, screening anti-HCV serology can be performed in patients at low risk for HCV and a nucleic acid test performed if serology is positive.
Baseline testing for the HCP should include anti-HCV testing and, if positive, HCV RNA testing is recommended. HCPs who test positive for HCV RNA at baseline are considered to have a preexisting HCV infection and should be referred for treatment.
Follow-up testing
For HCPs with exposure to blood or body fluids from a patient who is anti-HCV positive but HCV RNA negative, follow-up testing is not required.
If the source patient is HCV RNA positive, or if status of the source patient is unknown, the authors recommend that exposed HCPs have HCV RNA follow-up testing at 3-6 weeks post exposure, in addition to baseline testing. A final anti-HCV test is recommended at 4-6 months post exposure as there can be potential periods of aviremia during acute HCV infection.
Exposed HCPs who develop signs of illness indicative of HCV infection at any time should be tested for HCV RNA.
HCPs with positive HCV RNA test results should be referred for care and curative antiviral therapy.
Postexposure prophylaxis is not recommended
Recent data have shown that the risk for HCV infection from percutaneous exposure is 0.2% and from mucocutaneous exposure is 0%. On the basis of this information, the CDC guidelines no longer recommend routine postexposure prophylaxis for HCPs with occupational exposure to HCV. Rather, curative antiviral regimens should be reserved for instances of documented HCV transmission.
The authors disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The new guidance was developed in part as a result of an increase in the incidence of acute HCV infection in the United States, which increases the risk for occupational exposure among HCP. “[I]n certain health care settings, HCP might be exposed to source patients with early HCV infection before those patients develop serologic evidence of infection or symptoms indicative of viral hepatitis,” wrote the authors of the report, published online July 24 in the CDC’s Morbidity and Mortality Weekly Report.
The guidelines, which no longer recommend waiting for spontaneous resolution upon initial diagnosis, include recommendations and algorithms for baseline and follow-up testing, appropriate test type, and recommendations for clinical management. The recommendations were developed on the basis of a current literature review, expert opinion from subject matter experts, and recent guidance from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.
Baseline testing ASAP
Baseline testing of the source patient and the HCP should be performed as soon as possible, preferably within 48 hours of exposure. The source patient should be tested for HCV RNA using a nucleic acid test. Alternatively, screening anti-HCV serology can be performed in patients at low risk for HCV and a nucleic acid test performed if serology is positive.
Baseline testing for the HCP should include anti-HCV testing and, if positive, HCV RNA testing is recommended. HCPs who test positive for HCV RNA at baseline are considered to have a preexisting HCV infection and should be referred for treatment.
Follow-up testing
For HCPs with exposure to blood or body fluids from a patient who is anti-HCV positive but HCV RNA negative, follow-up testing is not required.
If the source patient is HCV RNA positive, or if status of the source patient is unknown, the authors recommend that exposed HCPs have HCV RNA follow-up testing at 3-6 weeks post exposure, in addition to baseline testing. A final anti-HCV test is recommended at 4-6 months post exposure as there can be potential periods of aviremia during acute HCV infection.
Exposed HCPs who develop signs of illness indicative of HCV infection at any time should be tested for HCV RNA.
HCPs with positive HCV RNA test results should be referred for care and curative antiviral therapy.
Postexposure prophylaxis is not recommended
Recent data have shown that the risk for HCV infection from percutaneous exposure is 0.2% and from mucocutaneous exposure is 0%. On the basis of this information, the CDC guidelines no longer recommend routine postexposure prophylaxis for HCPs with occupational exposure to HCV. Rather, curative antiviral regimens should be reserved for instances of documented HCV transmission.
The authors disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
FDA approves low-sodium treatment option for narcolepsy
Xywav is a novel oxybate product with a unique composition of cations, resulting in 92% less sodium than sodium oxybate (Xyrem, Jazz Pharmaceuticals) at the recommended dosage range of 6 to 9 grams, the company said in a news release.
The FDA approved the drug based on a phase 3 trial involving 201 patients who had narcolepsy with cataplexy.
As reported by Medscape Medical News from the World Sleep 2019 meeting, Xywav demonstrated highly statistically significant differences (P < .0001) in weekly number of cataplexy attacks (primary efficacy endpoint) and Epworth Sleepiness Scale scores (key secondary outcome) vs placebo.
“Based on the efficacy demonstrated in the clinical program, the approval of Xywav is important for people living with cataplexy or EDS associated with narcolepsy,” lead investigator Richard K. Bogan, MD, said in the company’s news release.
He noted that the average American consumes too much sodium. “Excess sodium intake has been linked with increases in blood pressure, hypertension, stroke, and other cardiovascular disease,” said Dr. Bogan, associate clinical professor at the University of South Carolina School of Medicine, Columbia.
“Xywav makes it possible for patients to have a lower-sodium oxybate treatment option. This may help patients taking sodium oxybate better align with daily sodium intake recommendations, including those by the American Heart Association,” he added.
The overall safety profile of Xywav is in line with sodium oxybate, the company said. The most common adverse reactions in adults, occurring in at least 5% of participants, were headache, nausea, dizziness, decreased appetite, parasomnia, diarrhea, hyperhidrosis (excessive sweating), anxiety, and vomiting.
Xywav has a boxed warning as a CNS depressant and for its potential for abuse and misuse. As a result, the drug is only available through a Risk Evaluation and Mitigation Strategy (REMS) program.
The US Drug Enforcement Agency has designated Xywav as a schedule III drug, meaning it has a moderate to low potential for physical and psychological dependence.
The company plans to launch Xywav by the end of the year. Full prescribing information and a medication guide are available online.
This article first appeared on Medscape.com.
Xywav is a novel oxybate product with a unique composition of cations, resulting in 92% less sodium than sodium oxybate (Xyrem, Jazz Pharmaceuticals) at the recommended dosage range of 6 to 9 grams, the company said in a news release.
The FDA approved the drug based on a phase 3 trial involving 201 patients who had narcolepsy with cataplexy.
As reported by Medscape Medical News from the World Sleep 2019 meeting, Xywav demonstrated highly statistically significant differences (P < .0001) in weekly number of cataplexy attacks (primary efficacy endpoint) and Epworth Sleepiness Scale scores (key secondary outcome) vs placebo.
“Based on the efficacy demonstrated in the clinical program, the approval of Xywav is important for people living with cataplexy or EDS associated with narcolepsy,” lead investigator Richard K. Bogan, MD, said in the company’s news release.
He noted that the average American consumes too much sodium. “Excess sodium intake has been linked with increases in blood pressure, hypertension, stroke, and other cardiovascular disease,” said Dr. Bogan, associate clinical professor at the University of South Carolina School of Medicine, Columbia.
“Xywav makes it possible for patients to have a lower-sodium oxybate treatment option. This may help patients taking sodium oxybate better align with daily sodium intake recommendations, including those by the American Heart Association,” he added.
The overall safety profile of Xywav is in line with sodium oxybate, the company said. The most common adverse reactions in adults, occurring in at least 5% of participants, were headache, nausea, dizziness, decreased appetite, parasomnia, diarrhea, hyperhidrosis (excessive sweating), anxiety, and vomiting.
Xywav has a boxed warning as a CNS depressant and for its potential for abuse and misuse. As a result, the drug is only available through a Risk Evaluation and Mitigation Strategy (REMS) program.
The US Drug Enforcement Agency has designated Xywav as a schedule III drug, meaning it has a moderate to low potential for physical and psychological dependence.
The company plans to launch Xywav by the end of the year. Full prescribing information and a medication guide are available online.
This article first appeared on Medscape.com.
Xywav is a novel oxybate product with a unique composition of cations, resulting in 92% less sodium than sodium oxybate (Xyrem, Jazz Pharmaceuticals) at the recommended dosage range of 6 to 9 grams, the company said in a news release.
The FDA approved the drug based on a phase 3 trial involving 201 patients who had narcolepsy with cataplexy.
As reported by Medscape Medical News from the World Sleep 2019 meeting, Xywav demonstrated highly statistically significant differences (P < .0001) in weekly number of cataplexy attacks (primary efficacy endpoint) and Epworth Sleepiness Scale scores (key secondary outcome) vs placebo.
“Based on the efficacy demonstrated in the clinical program, the approval of Xywav is important for people living with cataplexy or EDS associated with narcolepsy,” lead investigator Richard K. Bogan, MD, said in the company’s news release.
He noted that the average American consumes too much sodium. “Excess sodium intake has been linked with increases in blood pressure, hypertension, stroke, and other cardiovascular disease,” said Dr. Bogan, associate clinical professor at the University of South Carolina School of Medicine, Columbia.
“Xywav makes it possible for patients to have a lower-sodium oxybate treatment option. This may help patients taking sodium oxybate better align with daily sodium intake recommendations, including those by the American Heart Association,” he added.
The overall safety profile of Xywav is in line with sodium oxybate, the company said. The most common adverse reactions in adults, occurring in at least 5% of participants, were headache, nausea, dizziness, decreased appetite, parasomnia, diarrhea, hyperhidrosis (excessive sweating), anxiety, and vomiting.
Xywav has a boxed warning as a CNS depressant and for its potential for abuse and misuse. As a result, the drug is only available through a Risk Evaluation and Mitigation Strategy (REMS) program.
The US Drug Enforcement Agency has designated Xywav as a schedule III drug, meaning it has a moderate to low potential for physical and psychological dependence.
The company plans to launch Xywav by the end of the year. Full prescribing information and a medication guide are available online.
This article first appeared on Medscape.com.
CMS to broaden transcatheter mitral valve repair coverage, and change its name
The first order of business in the long-awaited, recently released Centers for Medicare & Medicaid Services (CMS) proposed national coverage decision (NCD) for transcatheter mitral valve repair (TMVR) was to get rid of its familiar moniker.
The document tosses the term TMVR in favor of transcatheter edge-to-edge repair (TEER) “to more precisely define the treatment addressed in this NCD” and differentiate it from other therapies that repair or replace the mitral valve.
(In an off-the-cuff Twitter poll launched right after the CMS document’s release, 80.3% of respondents answered that they “hate” the new acronym and the remainder said they “love” it; those two were the poll’s only choices.)
The NCD proposal goes on to say that CMS coverage of TEER would expand to include treatment of symptomatic moderate-to-severe or severe functional mitral regurgitation (MR) when used with maximally tolerated guideline-directed medical therapy.
The proposed NCD has been expected since March 2019 when the US Food and Drug Administration (FDA) approved the MitraClip (Abbott Vascular) for secondary functional MR. Medicare has covered MitraClip for primary degenerative MR since 2014.
Abbott announced in October 2019 that it would ramp up production of the MitraClip, which is currently the only FDA-approved TEER device.
Further specifications
Even as the new proposed NCD would add CMS coverage for functional MR, it would also decline a coverage statement for degenerative MR. Instead, it proposes to leave such coverage decisions to local Medical Administrative Contractors (MACs), given a relatively low incidence of clip intervention for degenerative MR. Less than 1% of the Medicare population undergo TEER of the mitral valve for that indication, the document says.
“The MACs are structured to be able to take into account local patient, physician, and institutional factors, which are especially important when overall prevalence is very low.”
The proposal also emphasizes that patients undergoing such covered TEER procedures be “under the care of a heart failure physician specialist experienced in the care and treatment of mitral valve disease,» with additional care provided by a heart team that includes a cardiac surgeon, interventional cardiologist, interventional echocardiographer.
The new document is generally consistent with a Consensus Statement from the American Association for Thoracic Surgery, the American College of Cardiology (ACC), the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons published in December 2019 and covered then by theheart.org / Medscape Cardiology.
In anticipation the CMS coverage proposal, the ACC earlier this year published a Focused Update of the 2017 Expert Consensus Decision Pathway on the Management of Mitral Regurgitation to reflect new evidence in the field, mainly the recent clinical trial data on functional MR from the MITRA-FR and COAPT trials.
“The proposed criteria are nicely guided by the multisociety consensus document, which sought to foster optimal patient outcomes while also maintaining access to TEER,” Sammy Elmariah, MD, MPH, from Massachusetts General Hospital in Boston, commented by email.
“These criteria, in conjunction with results of the COAPT trial, establish TEER as the standard of care for patients with symptomatic functional MR despite guideline-directed medical therapy who do not possess an alternative indication for cardiac surgery,” said Elmariah, a coauthor on both the Consensus Statement and the Focused Update.
The proposed NCD seems “reasonable,” cardiothoracic surgeon Michael J. Reardon, MD, Houston Methodist Hospital, said by email. But he thought there might be some objections to the requirement for TEER centers to have a surgery program with a minimum annual volume for mitral-valve surgeries.
The proposed NCD says a hospital must have “a surgical program that performs ≥25 total mitral valve surgical procedures for severe MR per year, of which at least 10 must be mitral valve repairs.”
“There is a very definite relationship between mitral valve surgery volume and surgical outcomes and between TEER volume and TEER outcomes, but no real relationship between mitral valve surgery volumes and TEER outcomes,” Reardon said. “A mitral valve surgery program is important, but how many cases do you need to be able to start and run a TEER program?”
Edwards Lifesciences is currently testing its own device for TEER: the PASCAL transcatheter mitral valve repair system. Early findings from the company’s ongoing CLASP IID trial, a head-to-head comparison of Pascal and MitraClip, are expected in December 2023.
CMS is seeking comments on the proposed national coverage determination, and will render a final decision within 60 days of the end of the 30-day public comment period.
Elmariah discloses receiving research grants from the American Heart Association, the National Institutes of Health, Edwards Lifesciences, Svelte Medical, and Medtronic, and consulting fees from AstraZeneca. Reardon recently reported no relevant conflicts of interest.
This article first appeared on Medscape.com.
The first order of business in the long-awaited, recently released Centers for Medicare & Medicaid Services (CMS) proposed national coverage decision (NCD) for transcatheter mitral valve repair (TMVR) was to get rid of its familiar moniker.
The document tosses the term TMVR in favor of transcatheter edge-to-edge repair (TEER) “to more precisely define the treatment addressed in this NCD” and differentiate it from other therapies that repair or replace the mitral valve.
(In an off-the-cuff Twitter poll launched right after the CMS document’s release, 80.3% of respondents answered that they “hate” the new acronym and the remainder said they “love” it; those two were the poll’s only choices.)
The NCD proposal goes on to say that CMS coverage of TEER would expand to include treatment of symptomatic moderate-to-severe or severe functional mitral regurgitation (MR) when used with maximally tolerated guideline-directed medical therapy.
The proposed NCD has been expected since March 2019 when the US Food and Drug Administration (FDA) approved the MitraClip (Abbott Vascular) for secondary functional MR. Medicare has covered MitraClip for primary degenerative MR since 2014.
Abbott announced in October 2019 that it would ramp up production of the MitraClip, which is currently the only FDA-approved TEER device.
Further specifications
Even as the new proposed NCD would add CMS coverage for functional MR, it would also decline a coverage statement for degenerative MR. Instead, it proposes to leave such coverage decisions to local Medical Administrative Contractors (MACs), given a relatively low incidence of clip intervention for degenerative MR. Less than 1% of the Medicare population undergo TEER of the mitral valve for that indication, the document says.
“The MACs are structured to be able to take into account local patient, physician, and institutional factors, which are especially important when overall prevalence is very low.”
The proposal also emphasizes that patients undergoing such covered TEER procedures be “under the care of a heart failure physician specialist experienced in the care and treatment of mitral valve disease,» with additional care provided by a heart team that includes a cardiac surgeon, interventional cardiologist, interventional echocardiographer.
The new document is generally consistent with a Consensus Statement from the American Association for Thoracic Surgery, the American College of Cardiology (ACC), the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons published in December 2019 and covered then by theheart.org / Medscape Cardiology.
In anticipation the CMS coverage proposal, the ACC earlier this year published a Focused Update of the 2017 Expert Consensus Decision Pathway on the Management of Mitral Regurgitation to reflect new evidence in the field, mainly the recent clinical trial data on functional MR from the MITRA-FR and COAPT trials.
“The proposed criteria are nicely guided by the multisociety consensus document, which sought to foster optimal patient outcomes while also maintaining access to TEER,” Sammy Elmariah, MD, MPH, from Massachusetts General Hospital in Boston, commented by email.
“These criteria, in conjunction with results of the COAPT trial, establish TEER as the standard of care for patients with symptomatic functional MR despite guideline-directed medical therapy who do not possess an alternative indication for cardiac surgery,” said Elmariah, a coauthor on both the Consensus Statement and the Focused Update.
The proposed NCD seems “reasonable,” cardiothoracic surgeon Michael J. Reardon, MD, Houston Methodist Hospital, said by email. But he thought there might be some objections to the requirement for TEER centers to have a surgery program with a minimum annual volume for mitral-valve surgeries.
The proposed NCD says a hospital must have “a surgical program that performs ≥25 total mitral valve surgical procedures for severe MR per year, of which at least 10 must be mitral valve repairs.”
“There is a very definite relationship between mitral valve surgery volume and surgical outcomes and between TEER volume and TEER outcomes, but no real relationship between mitral valve surgery volumes and TEER outcomes,” Reardon said. “A mitral valve surgery program is important, but how many cases do you need to be able to start and run a TEER program?”
Edwards Lifesciences is currently testing its own device for TEER: the PASCAL transcatheter mitral valve repair system. Early findings from the company’s ongoing CLASP IID trial, a head-to-head comparison of Pascal and MitraClip, are expected in December 2023.
CMS is seeking comments on the proposed national coverage determination, and will render a final decision within 60 days of the end of the 30-day public comment period.
Elmariah discloses receiving research grants from the American Heart Association, the National Institutes of Health, Edwards Lifesciences, Svelte Medical, and Medtronic, and consulting fees from AstraZeneca. Reardon recently reported no relevant conflicts of interest.
This article first appeared on Medscape.com.
The first order of business in the long-awaited, recently released Centers for Medicare & Medicaid Services (CMS) proposed national coverage decision (NCD) for transcatheter mitral valve repair (TMVR) was to get rid of its familiar moniker.
The document tosses the term TMVR in favor of transcatheter edge-to-edge repair (TEER) “to more precisely define the treatment addressed in this NCD” and differentiate it from other therapies that repair or replace the mitral valve.
(In an off-the-cuff Twitter poll launched right after the CMS document’s release, 80.3% of respondents answered that they “hate” the new acronym and the remainder said they “love” it; those two were the poll’s only choices.)
The NCD proposal goes on to say that CMS coverage of TEER would expand to include treatment of symptomatic moderate-to-severe or severe functional mitral regurgitation (MR) when used with maximally tolerated guideline-directed medical therapy.
The proposed NCD has been expected since March 2019 when the US Food and Drug Administration (FDA) approved the MitraClip (Abbott Vascular) for secondary functional MR. Medicare has covered MitraClip for primary degenerative MR since 2014.
Abbott announced in October 2019 that it would ramp up production of the MitraClip, which is currently the only FDA-approved TEER device.
Further specifications
Even as the new proposed NCD would add CMS coverage for functional MR, it would also decline a coverage statement for degenerative MR. Instead, it proposes to leave such coverage decisions to local Medical Administrative Contractors (MACs), given a relatively low incidence of clip intervention for degenerative MR. Less than 1% of the Medicare population undergo TEER of the mitral valve for that indication, the document says.
“The MACs are structured to be able to take into account local patient, physician, and institutional factors, which are especially important when overall prevalence is very low.”
The proposal also emphasizes that patients undergoing such covered TEER procedures be “under the care of a heart failure physician specialist experienced in the care and treatment of mitral valve disease,» with additional care provided by a heart team that includes a cardiac surgeon, interventional cardiologist, interventional echocardiographer.
The new document is generally consistent with a Consensus Statement from the American Association for Thoracic Surgery, the American College of Cardiology (ACC), the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons published in December 2019 and covered then by theheart.org / Medscape Cardiology.
In anticipation the CMS coverage proposal, the ACC earlier this year published a Focused Update of the 2017 Expert Consensus Decision Pathway on the Management of Mitral Regurgitation to reflect new evidence in the field, mainly the recent clinical trial data on functional MR from the MITRA-FR and COAPT trials.
“The proposed criteria are nicely guided by the multisociety consensus document, which sought to foster optimal patient outcomes while also maintaining access to TEER,” Sammy Elmariah, MD, MPH, from Massachusetts General Hospital in Boston, commented by email.
“These criteria, in conjunction with results of the COAPT trial, establish TEER as the standard of care for patients with symptomatic functional MR despite guideline-directed medical therapy who do not possess an alternative indication for cardiac surgery,” said Elmariah, a coauthor on both the Consensus Statement and the Focused Update.
The proposed NCD seems “reasonable,” cardiothoracic surgeon Michael J. Reardon, MD, Houston Methodist Hospital, said by email. But he thought there might be some objections to the requirement for TEER centers to have a surgery program with a minimum annual volume for mitral-valve surgeries.
The proposed NCD says a hospital must have “a surgical program that performs ≥25 total mitral valve surgical procedures for severe MR per year, of which at least 10 must be mitral valve repairs.”
“There is a very definite relationship between mitral valve surgery volume and surgical outcomes and between TEER volume and TEER outcomes, but no real relationship between mitral valve surgery volumes and TEER outcomes,” Reardon said. “A mitral valve surgery program is important, but how many cases do you need to be able to start and run a TEER program?”
Edwards Lifesciences is currently testing its own device for TEER: the PASCAL transcatheter mitral valve repair system. Early findings from the company’s ongoing CLASP IID trial, a head-to-head comparison of Pascal and MitraClip, are expected in December 2023.
CMS is seeking comments on the proposed national coverage determination, and will render a final decision within 60 days of the end of the 30-day public comment period.
Elmariah discloses receiving research grants from the American Heart Association, the National Institutes of Health, Edwards Lifesciences, Svelte Medical, and Medtronic, and consulting fees from AstraZeneca. Reardon recently reported no relevant conflicts of interest.
This article first appeared on Medscape.com.
Terlipressin squeaks by FDA review for hepatorenal syndrome 1
The Food and Drug Administration’s Cardiovascular and Renal Drugs Advisory Committee narrowly recommended, by an 8-7 vote, that the agency grant marketing approval to terlipressin for the treatment of hepatorenal syndrome type 1, a severe, rare, and often rapidly lethal disease. No drugs are currently licensed in the United States for this indication.
The advisory committee’s discussion and vote on July 15 showcased the struggle the 15 members faced parsing data that hinted at efficacy but also featured clear flaws and limitations, with meager evidence showing clinically meaningful patient improvements.
Several advisory committee members voiced their dilemma balancing the desperation of patients and clinicians to have an effective agent to treat a frequently fatal condition against spotty evidence of efficacy.
Their uncertainty over benefit was exacerbated by the substantial rate of serious adverse events, compared with placebo. These events included respiratory failure, which occurred an absolute 9% more often among patients treated with terlipressin than among those who received placebo in the drug’s recent pivotal trial, and sepsis and septic shock, with an absolute 7% excess rate with terlipressin in comparison with placebo.
“This is an important, unmet need, and I want this drug, but the data are not clear that the benefits outweigh the risks,” commented Steven F. Solga, MD, a transplant hepatologist at the University of Pennsylvania, Philadelphia, who is a committee member.
“When you have sick patients with few treatment options, you grope for something to use, but I worry that this won’t help patients,” he said when explaining his vote against approval.
“I look forward to using this medication if I could figure out which patients could benefit from it,” he said.
‘Allow patients to decide if they want this treatment’
Experts estimate that the annual incidence of hepatorenal syndrome type 1 in the United States is about 35,000 patients.
“I would have liked to vote yes, because terlipressin was associated with a short-term increase in renal function, but there was also clear evidence for the risk of sepsis and respiratory failure, and no evidence that it improved survival,” said panel member Patrick H. Nachman, MD.
Dr. Nachman, professor of medicine and director of the division of nephrology and hypertension at the University of Minnesota, Minneapolis, voted against approval.
Several who voted in favor of terlipressin also shared these misgivings.
“The trend for benefit was quite small, I’m very worried about respiratory failure, and I’m uncomfortable with the postrandomization analyses” used by the developer of terlipressin (Mallinckrodt) to buttress the efficacy claims, explained panel member Paul M. Ridker, MD.
“So why did I vote yes? The problem is the enormous unmet need. Patients are in desperate shape, and the standard treatments are used off label, with no data. Here, we have data, and the primary endpoint was met,” said Dr. Ridker, who is professor of medicine at Harvard Medical School and director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, both in Boston.
The effects of terlipressin appear to give clinicians a way to “stabilize renal function and buy time,” making it more feasible to try to rush the patient to liver transplantation or at least to “stop their downward spiral» as patients with decompensated liver failure develop inadequate renal blood flow that produces an acute fall in kidney function,” explained David N. Assis, MD, a hepatologist at Yale University, New Haven, Conn.
“The reality is, nothing else is available, aside from renal replacement therapy and pressors. There is a need for a treatment that buys time,” he said. He voted to recommend approval.
That sentiment was notably echoed in comments from the two nonclinical members of the advisory committee.
“This treatment addresses a major gap in care,” said Jacqueline D. Alikhaani, the panel’s consumer representative. “Allow patients to decide if they want this treatment,” said Daniel Bonner, the committee’s patient representative. Both voted in favor of FDA approval.
Terlipressin has been a long-standing linchpin for treating hepatorenal syndrome type 1 in Europe and other places outside the United States and Canada.
The most recent guidelines for managing patients with decompensated cirrhosis from the European Association for the Study of the Liver say that “[t]erlipressin plus albumin should be considered as the first-line therapeutic option for the treatment of hepatorenal syndrome and acute kidney injury” (J Hepatol. 2018 Aug 1;69).
According to company representatives who presented the case for terlipressin during the meeting, bringing the drug onto the U.S. market has been a 17-year journey, featuring three sequential trials.
- A 112-patient that the FDA accepted as the first of the two supportive trials needed for approval.
- A with 196 patients that tested terlipressin plus albumin against placebo plus albumin and showed a nominal benefit from terlipressin that failed to achieve statistical significance.
- The most recent trial, , which directly led to the advisory committee session. That trial enrolled 300 patients and met its primary endpoint. Data have not yet been published but have been at meetings.
One of the sources of controversy over the benefit from terlipressin centered on the primary endpoint used in CONFIRM, which required that the patient have two consecutive, low readings for serum creatinine, with levels no greater than 1.5 mg/dL while on treatment, and remain alive and free from need for renal replacement therapy for at least 10 days beyond this.
The FDA agreed to accept this as a primary endpoint but nonetheless considered it a surrogate.
According to FDA staffers who presented their take on the application, the agency accepted this primary endpoint “with the understanding that favorable trends in clinical outcomes, thought to be predicted by successful treatment of hepatic renal syndrome type 1, would be expected.”
The lack of many favorable trends in clinical outcomes helped foster the advisory committee’s divided response. The FDA’s staff uses its discretion when considering an advisory committee’s recommendations and making a final determination.
None of the advisory committee members disclosed any relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration’s Cardiovascular and Renal Drugs Advisory Committee narrowly recommended, by an 8-7 vote, that the agency grant marketing approval to terlipressin for the treatment of hepatorenal syndrome type 1, a severe, rare, and often rapidly lethal disease. No drugs are currently licensed in the United States for this indication.
The advisory committee’s discussion and vote on July 15 showcased the struggle the 15 members faced parsing data that hinted at efficacy but also featured clear flaws and limitations, with meager evidence showing clinically meaningful patient improvements.
Several advisory committee members voiced their dilemma balancing the desperation of patients and clinicians to have an effective agent to treat a frequently fatal condition against spotty evidence of efficacy.
Their uncertainty over benefit was exacerbated by the substantial rate of serious adverse events, compared with placebo. These events included respiratory failure, which occurred an absolute 9% more often among patients treated with terlipressin than among those who received placebo in the drug’s recent pivotal trial, and sepsis and septic shock, with an absolute 7% excess rate with terlipressin in comparison with placebo.
“This is an important, unmet need, and I want this drug, but the data are not clear that the benefits outweigh the risks,” commented Steven F. Solga, MD, a transplant hepatologist at the University of Pennsylvania, Philadelphia, who is a committee member.
“When you have sick patients with few treatment options, you grope for something to use, but I worry that this won’t help patients,” he said when explaining his vote against approval.
“I look forward to using this medication if I could figure out which patients could benefit from it,” he said.
‘Allow patients to decide if they want this treatment’
Experts estimate that the annual incidence of hepatorenal syndrome type 1 in the United States is about 35,000 patients.
“I would have liked to vote yes, because terlipressin was associated with a short-term increase in renal function, but there was also clear evidence for the risk of sepsis and respiratory failure, and no evidence that it improved survival,” said panel member Patrick H. Nachman, MD.
Dr. Nachman, professor of medicine and director of the division of nephrology and hypertension at the University of Minnesota, Minneapolis, voted against approval.
Several who voted in favor of terlipressin also shared these misgivings.
“The trend for benefit was quite small, I’m very worried about respiratory failure, and I’m uncomfortable with the postrandomization analyses” used by the developer of terlipressin (Mallinckrodt) to buttress the efficacy claims, explained panel member Paul M. Ridker, MD.
“So why did I vote yes? The problem is the enormous unmet need. Patients are in desperate shape, and the standard treatments are used off label, with no data. Here, we have data, and the primary endpoint was met,” said Dr. Ridker, who is professor of medicine at Harvard Medical School and director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, both in Boston.
The effects of terlipressin appear to give clinicians a way to “stabilize renal function and buy time,” making it more feasible to try to rush the patient to liver transplantation or at least to “stop their downward spiral» as patients with decompensated liver failure develop inadequate renal blood flow that produces an acute fall in kidney function,” explained David N. Assis, MD, a hepatologist at Yale University, New Haven, Conn.
“The reality is, nothing else is available, aside from renal replacement therapy and pressors. There is a need for a treatment that buys time,” he said. He voted to recommend approval.
That sentiment was notably echoed in comments from the two nonclinical members of the advisory committee.
“This treatment addresses a major gap in care,” said Jacqueline D. Alikhaani, the panel’s consumer representative. “Allow patients to decide if they want this treatment,” said Daniel Bonner, the committee’s patient representative. Both voted in favor of FDA approval.
Terlipressin has been a long-standing linchpin for treating hepatorenal syndrome type 1 in Europe and other places outside the United States and Canada.
The most recent guidelines for managing patients with decompensated cirrhosis from the European Association for the Study of the Liver say that “[t]erlipressin plus albumin should be considered as the first-line therapeutic option for the treatment of hepatorenal syndrome and acute kidney injury” (J Hepatol. 2018 Aug 1;69).
According to company representatives who presented the case for terlipressin during the meeting, bringing the drug onto the U.S. market has been a 17-year journey, featuring three sequential trials.
- A 112-patient that the FDA accepted as the first of the two supportive trials needed for approval.
- A with 196 patients that tested terlipressin plus albumin against placebo plus albumin and showed a nominal benefit from terlipressin that failed to achieve statistical significance.
- The most recent trial, , which directly led to the advisory committee session. That trial enrolled 300 patients and met its primary endpoint. Data have not yet been published but have been at meetings.
One of the sources of controversy over the benefit from terlipressin centered on the primary endpoint used in CONFIRM, which required that the patient have two consecutive, low readings for serum creatinine, with levels no greater than 1.5 mg/dL while on treatment, and remain alive and free from need for renal replacement therapy for at least 10 days beyond this.
The FDA agreed to accept this as a primary endpoint but nonetheless considered it a surrogate.
According to FDA staffers who presented their take on the application, the agency accepted this primary endpoint “with the understanding that favorable trends in clinical outcomes, thought to be predicted by successful treatment of hepatic renal syndrome type 1, would be expected.”
The lack of many favorable trends in clinical outcomes helped foster the advisory committee’s divided response. The FDA’s staff uses its discretion when considering an advisory committee’s recommendations and making a final determination.
None of the advisory committee members disclosed any relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration’s Cardiovascular and Renal Drugs Advisory Committee narrowly recommended, by an 8-7 vote, that the agency grant marketing approval to terlipressin for the treatment of hepatorenal syndrome type 1, a severe, rare, and often rapidly lethal disease. No drugs are currently licensed in the United States for this indication.
The advisory committee’s discussion and vote on July 15 showcased the struggle the 15 members faced parsing data that hinted at efficacy but also featured clear flaws and limitations, with meager evidence showing clinically meaningful patient improvements.
Several advisory committee members voiced their dilemma balancing the desperation of patients and clinicians to have an effective agent to treat a frequently fatal condition against spotty evidence of efficacy.
Their uncertainty over benefit was exacerbated by the substantial rate of serious adverse events, compared with placebo. These events included respiratory failure, which occurred an absolute 9% more often among patients treated with terlipressin than among those who received placebo in the drug’s recent pivotal trial, and sepsis and septic shock, with an absolute 7% excess rate with terlipressin in comparison with placebo.
“This is an important, unmet need, and I want this drug, but the data are not clear that the benefits outweigh the risks,” commented Steven F. Solga, MD, a transplant hepatologist at the University of Pennsylvania, Philadelphia, who is a committee member.
“When you have sick patients with few treatment options, you grope for something to use, but I worry that this won’t help patients,” he said when explaining his vote against approval.
“I look forward to using this medication if I could figure out which patients could benefit from it,” he said.
‘Allow patients to decide if they want this treatment’
Experts estimate that the annual incidence of hepatorenal syndrome type 1 in the United States is about 35,000 patients.
“I would have liked to vote yes, because terlipressin was associated with a short-term increase in renal function, but there was also clear evidence for the risk of sepsis and respiratory failure, and no evidence that it improved survival,” said panel member Patrick H. Nachman, MD.
Dr. Nachman, professor of medicine and director of the division of nephrology and hypertension at the University of Minnesota, Minneapolis, voted against approval.
Several who voted in favor of terlipressin also shared these misgivings.
“The trend for benefit was quite small, I’m very worried about respiratory failure, and I’m uncomfortable with the postrandomization analyses” used by the developer of terlipressin (Mallinckrodt) to buttress the efficacy claims, explained panel member Paul M. Ridker, MD.
“So why did I vote yes? The problem is the enormous unmet need. Patients are in desperate shape, and the standard treatments are used off label, with no data. Here, we have data, and the primary endpoint was met,” said Dr. Ridker, who is professor of medicine at Harvard Medical School and director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, both in Boston.
The effects of terlipressin appear to give clinicians a way to “stabilize renal function and buy time,” making it more feasible to try to rush the patient to liver transplantation or at least to “stop their downward spiral» as patients with decompensated liver failure develop inadequate renal blood flow that produces an acute fall in kidney function,” explained David N. Assis, MD, a hepatologist at Yale University, New Haven, Conn.
“The reality is, nothing else is available, aside from renal replacement therapy and pressors. There is a need for a treatment that buys time,” he said. He voted to recommend approval.
That sentiment was notably echoed in comments from the two nonclinical members of the advisory committee.
“This treatment addresses a major gap in care,” said Jacqueline D. Alikhaani, the panel’s consumer representative. “Allow patients to decide if they want this treatment,” said Daniel Bonner, the committee’s patient representative. Both voted in favor of FDA approval.
Terlipressin has been a long-standing linchpin for treating hepatorenal syndrome type 1 in Europe and other places outside the United States and Canada.
The most recent guidelines for managing patients with decompensated cirrhosis from the European Association for the Study of the Liver say that “[t]erlipressin plus albumin should be considered as the first-line therapeutic option for the treatment of hepatorenal syndrome and acute kidney injury” (J Hepatol. 2018 Aug 1;69).
According to company representatives who presented the case for terlipressin during the meeting, bringing the drug onto the U.S. market has been a 17-year journey, featuring three sequential trials.
- A 112-patient that the FDA accepted as the first of the two supportive trials needed for approval.
- A with 196 patients that tested terlipressin plus albumin against placebo plus albumin and showed a nominal benefit from terlipressin that failed to achieve statistical significance.
- The most recent trial, , which directly led to the advisory committee session. That trial enrolled 300 patients and met its primary endpoint. Data have not yet been published but have been at meetings.
One of the sources of controversy over the benefit from terlipressin centered on the primary endpoint used in CONFIRM, which required that the patient have two consecutive, low readings for serum creatinine, with levels no greater than 1.5 mg/dL while on treatment, and remain alive and free from need for renal replacement therapy for at least 10 days beyond this.
The FDA agreed to accept this as a primary endpoint but nonetheless considered it a surrogate.
According to FDA staffers who presented their take on the application, the agency accepted this primary endpoint “with the understanding that favorable trends in clinical outcomes, thought to be predicted by successful treatment of hepatic renal syndrome type 1, would be expected.”
The lack of many favorable trends in clinical outcomes helped foster the advisory committee’s divided response. The FDA’s staff uses its discretion when considering an advisory committee’s recommendations and making a final determination.
None of the advisory committee members disclosed any relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FDA approves Tremfya (guselkumab) for psoriatic arthritis
, according to a July 14 announcement from its manufacturer, Janssen.
The FDA’s approval marks the second indication for guselkumab, which was first approved for adults with plaque psoriasis in 2017.
The agency based its approval on two pivotal phase 3 clinical trials, DISCOVER-1 and DISCOVER-2, which tested the biologic in 1,120 adults with active PsA who were naive to biologics (both trials) or had an inadequate response or intolerance to one or two tumor necrosis factor inhibitors (in about 30% of patients in DISCOVER-1). Part of this pretrial standard treatment could include at least 4 months of Otezla (apremilast), at least 3 months of nonbiologic disease-modifying antirheumatic drugs (DMARDs), or at least 4 weeks of NSAIDs. In both trials, about 58% of patients took methotrexate.
Participants who took guselkumab achieved 20% improvement in American College of Rheumatology response criteria at week 24 at rates of 52% in DISCOVER-1 and 64% in DISCOVER-2, whereas placebo-treated patients had rates of 22% and 33%, respectively.
Guselkumab improved patients’ other symptoms, including skin manifestations of psoriasis, physical functioning, enthesitis, dactylitis, and fatigue, according to the Janssen release.
Guselkumab, a fully human monoclonal antibody that selectively binds to the p19 subunit of IL-23, is administered as a 100-mg subcutaneous injection every 8 weeks, following two starter doses at weeks 0 and 4, and can be used alone or in combination with a conventional DMARD.
In guselkumab clinical trials of patients with PsA, a minority had bronchitis or a decreased neutrophil count, but the safety profile was otherwise generally consistent with what has been seen in patients with plaque psoriasis, according to the company release. Other common side effects described in 1% or more of patients have included upper respiratory infections, headache, injection-site reactions, arthralgia, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections.
, according to a July 14 announcement from its manufacturer, Janssen.
The FDA’s approval marks the second indication for guselkumab, which was first approved for adults with plaque psoriasis in 2017.
The agency based its approval on two pivotal phase 3 clinical trials, DISCOVER-1 and DISCOVER-2, which tested the biologic in 1,120 adults with active PsA who were naive to biologics (both trials) or had an inadequate response or intolerance to one or two tumor necrosis factor inhibitors (in about 30% of patients in DISCOVER-1). Part of this pretrial standard treatment could include at least 4 months of Otezla (apremilast), at least 3 months of nonbiologic disease-modifying antirheumatic drugs (DMARDs), or at least 4 weeks of NSAIDs. In both trials, about 58% of patients took methotrexate.
Participants who took guselkumab achieved 20% improvement in American College of Rheumatology response criteria at week 24 at rates of 52% in DISCOVER-1 and 64% in DISCOVER-2, whereas placebo-treated patients had rates of 22% and 33%, respectively.
Guselkumab improved patients’ other symptoms, including skin manifestations of psoriasis, physical functioning, enthesitis, dactylitis, and fatigue, according to the Janssen release.
Guselkumab, a fully human monoclonal antibody that selectively binds to the p19 subunit of IL-23, is administered as a 100-mg subcutaneous injection every 8 weeks, following two starter doses at weeks 0 and 4, and can be used alone or in combination with a conventional DMARD.
In guselkumab clinical trials of patients with PsA, a minority had bronchitis or a decreased neutrophil count, but the safety profile was otherwise generally consistent with what has been seen in patients with plaque psoriasis, according to the company release. Other common side effects described in 1% or more of patients have included upper respiratory infections, headache, injection-site reactions, arthralgia, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections.
, according to a July 14 announcement from its manufacturer, Janssen.
The FDA’s approval marks the second indication for guselkumab, which was first approved for adults with plaque psoriasis in 2017.
The agency based its approval on two pivotal phase 3 clinical trials, DISCOVER-1 and DISCOVER-2, which tested the biologic in 1,120 adults with active PsA who were naive to biologics (both trials) or had an inadequate response or intolerance to one or two tumor necrosis factor inhibitors (in about 30% of patients in DISCOVER-1). Part of this pretrial standard treatment could include at least 4 months of Otezla (apremilast), at least 3 months of nonbiologic disease-modifying antirheumatic drugs (DMARDs), or at least 4 weeks of NSAIDs. In both trials, about 58% of patients took methotrexate.
Participants who took guselkumab achieved 20% improvement in American College of Rheumatology response criteria at week 24 at rates of 52% in DISCOVER-1 and 64% in DISCOVER-2, whereas placebo-treated patients had rates of 22% and 33%, respectively.
Guselkumab improved patients’ other symptoms, including skin manifestations of psoriasis, physical functioning, enthesitis, dactylitis, and fatigue, according to the Janssen release.
Guselkumab, a fully human monoclonal antibody that selectively binds to the p19 subunit of IL-23, is administered as a 100-mg subcutaneous injection every 8 weeks, following two starter doses at weeks 0 and 4, and can be used alone or in combination with a conventional DMARD.
In guselkumab clinical trials of patients with PsA, a minority had bronchitis or a decreased neutrophil count, but the safety profile was otherwise generally consistent with what has been seen in patients with plaque psoriasis, according to the company release. Other common side effects described in 1% or more of patients have included upper respiratory infections, headache, injection-site reactions, arthralgia, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections.
FDA approves oral therapy for myelodysplastic syndromes, CMML
The Food and Drug Administration has approved Inqovi (decitabine and cedazuridine tablets, Astex Pharmaceuticals) to treat adults with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML).
Approval of the tablets could obviate the need for some patients to come to healthcare settings for intravenous therapy, a consideration that goes beyond patient convenience. “The FDA remains committed to providing additional treatments to patients during the coronavirus pandemic. In this case, the FDA is making available an oral outpatient treatment option that can reduce the need for frequent visits to health care facilities,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, stated in a news release.
“At this critical time, we continue to focus on providing options to patients with cancer, including regimens that can be taken at home,” added Dr. Pazdur, who is also acting director of the office of oncologic diseases in the FDA’s Center for Drug Evaluation and Research.
Inqovi received an Orphan Drug designation and a Priority Review from the agency.
The FDA based the new formulation approval on clinical trials that showed patients taking Inqovi had similar drug concentrations, compared with others receiving intravenous decitabine.
The two therapies also had similar safety profiles. Fatigue, constipation, hemorrhage, muscle pain, mucositis, arthralgia, nausea, and fever with low white blood cell count were common side effects reported in people taking Inqovi. The agency noted that Inqovi can cause fetal harm, and that both male and female patients of reproductive age are advised to use effective contraception.
In the clinical trials, approximately half of the patients formerly dependent on transfusions no longer required them during an 8-week period.
Inqovi is taken as one tablet by mouth once daily for 5 consecutive days of each 28-day cycle.
The Food and Drug Administration has approved Inqovi (decitabine and cedazuridine tablets, Astex Pharmaceuticals) to treat adults with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML).
Approval of the tablets could obviate the need for some patients to come to healthcare settings for intravenous therapy, a consideration that goes beyond patient convenience. “The FDA remains committed to providing additional treatments to patients during the coronavirus pandemic. In this case, the FDA is making available an oral outpatient treatment option that can reduce the need for frequent visits to health care facilities,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, stated in a news release.
“At this critical time, we continue to focus on providing options to patients with cancer, including regimens that can be taken at home,” added Dr. Pazdur, who is also acting director of the office of oncologic diseases in the FDA’s Center for Drug Evaluation and Research.
Inqovi received an Orphan Drug designation and a Priority Review from the agency.
The FDA based the new formulation approval on clinical trials that showed patients taking Inqovi had similar drug concentrations, compared with others receiving intravenous decitabine.
The two therapies also had similar safety profiles. Fatigue, constipation, hemorrhage, muscle pain, mucositis, arthralgia, nausea, and fever with low white blood cell count were common side effects reported in people taking Inqovi. The agency noted that Inqovi can cause fetal harm, and that both male and female patients of reproductive age are advised to use effective contraception.
In the clinical trials, approximately half of the patients formerly dependent on transfusions no longer required them during an 8-week period.
Inqovi is taken as one tablet by mouth once daily for 5 consecutive days of each 28-day cycle.
The Food and Drug Administration has approved Inqovi (decitabine and cedazuridine tablets, Astex Pharmaceuticals) to treat adults with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML).
Approval of the tablets could obviate the need for some patients to come to healthcare settings for intravenous therapy, a consideration that goes beyond patient convenience. “The FDA remains committed to providing additional treatments to patients during the coronavirus pandemic. In this case, the FDA is making available an oral outpatient treatment option that can reduce the need for frequent visits to health care facilities,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, stated in a news release.
“At this critical time, we continue to focus on providing options to patients with cancer, including regimens that can be taken at home,” added Dr. Pazdur, who is also acting director of the office of oncologic diseases in the FDA’s Center for Drug Evaluation and Research.
Inqovi received an Orphan Drug designation and a Priority Review from the agency.
The FDA based the new formulation approval on clinical trials that showed patients taking Inqovi had similar drug concentrations, compared with others receiving intravenous decitabine.
The two therapies also had similar safety profiles. Fatigue, constipation, hemorrhage, muscle pain, mucositis, arthralgia, nausea, and fever with low white blood cell count were common side effects reported in people taking Inqovi. The agency noted that Inqovi can cause fetal harm, and that both male and female patients of reproductive age are advised to use effective contraception.
In the clinical trials, approximately half of the patients formerly dependent on transfusions no longer required them during an 8-week period.
Inqovi is taken as one tablet by mouth once daily for 5 consecutive days of each 28-day cycle.