Victoria Stern

Last month, the United States Food and Drug Administration (FDA) approved two new drugs and two biosimilars as well as halted commercialization for a hemophilia treatment.

Here’s a deeper look of what happened last month.

 

New Drugs

1. The FDA has approved mirdametinib (Gomekli, SpringWorks Therapeutics, Inc.) for adult and pediatric patients 2 years or older with neurofibromatosis type 1 and symptomatic plexiform neurofibromas that are not amenable to complete resection.

Approval for this agent was based on overall response rate findings from a multicenter, single-arm, phase 2b trial. The trial, which enrolled 58 adults and 56 pediatric patients with this rare disease, reported confirmed overall response rates of 41% among adults and 52% among children.

Adverse reactions occurring in at least 25% of adults included rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. Mirdametinib can also cause ocular toxicity. Treatment should be withheld, discontinued, or the dosage reduced based on the severity of these adverse reactions, according to the FDA notice.

2. The FDA has approved vimseltinib (Romvimza, Deciphera Pharmaceuticals, LLC) to treat adult patients with symptomatic tenosynovial giant cell tumors who will not benefit from surgical resection.

Vimseltinib was approved based on findings from the MOTION trial, which included 123 patients randomly assigned 2:1 to vimseltinib 30 mg twice weekly or to placebo for 24 weeks. At 25 weeks, the objective response rate was 40% in the vimseltinib arm and 0% in the placebo arm. The median duration of response was not reached in the vimseltinib arm. Patients receiving vimseltinib also demonstrated significant improvements in active range of motion, physical functioning, and pain at this time. After another 6 months of follow-up, 58% of responders had a duration of response of 9 months or longer.

Treatment-emergent adverse events in MOTION were largely of grade 1 or 2. The most common adverse reactions, occurring in at least 20% of patients, included increased aspartate aminotransferase, periorbital edema, fatigue, rash, and cholesterol.

 

New or Expanded Indications

1. The FDA has approved a supplemental Biologics License Application for brentuximab vedotin (Adcetris, Seagen Inc.), in combination with lenalidomide and rituximab, for adults with relapsed or refractory large B-cell lymphoma, after at least two prior lines of therapy, who are ineligible for stem cell transplant or chimeric antigen receptor T-cell therapy. This includes patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma.

Approval was based on the randomized, double-blind, placebo-controlled ECHELON-3 trial, which randomly assigned patients 1:1 to receive lenalidomide and rituximab plus either brentuximab vedotin or placebo until disease progression or unacceptable toxicity. Researchers reported a median overall survival of 13.8 months in the treatment group vs 8.5 months in the placebo group (hazard ratio, 0.63).

2. The FDA has approved the Biologics License Application for Ospomyv and Xbryk (Samsung Bioepis Co.) — biosimilars referencing denosumab (Prolia and Xgeva, respectively) — to treat osteoporosis and cancer-related bone loss.

Ospomyv and Xbryk have been approved for use in all indications of the approved reference drugs. Specifically, Xbryk is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors or multiple myeloma, and Ospomyv is indicated in several populations of patients with osteoporosis at high risk for fracture.

“The FDA approval of Ospomyv and Xbryk marks a key step in improving patient access and alleviating treatment cost for patients with osteoporosis and cancer-related bone loss in the United States,” Byoungin Jung, vice president at Samsung Bioepis, said in the news release.

 

Drug Commercialization Halt

Pfizer announced last month that it will halt the global development and commercialization of its hemophilia gene therapy fidanacogene elaparvovec (Beqvez). The company cited several reasons for the discontinuation, including low demand from patients and doctors.

Beqvez is a one-time therapy approved in the United States last April to treat adults with moderate to severe hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 men in the United States.

The significant price tag is one reason hematologists have cited for the low uptake. Another barrier is that “we don’t know the long-term outcomes” associated with the drug, pediatric hematologist Ben Samelson-Jones, MD, PhD, of the Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia, Philadelphia, told this news organization earlier this year.

Other issues include the prospect of newer treatment advances in the hemophilia space and logistical challenges. “There’s just a lot of logistics to getting an institution ready to provide this type of therapy,” Samelson-Jones added.

A version of this article first appeared on Medscape.com.

Last month, the United States Food and Drug Administration (FDA) approved two new drugs and two biosimilars as well as halted commercialization for a hemophilia treatment.

Here’s a deeper look of what happened last month.

 

New Drugs

1. The FDA has approved mirdametinib (Gomekli, SpringWorks Therapeutics, Inc.) for adult and pediatric patients 2 years or older with neurofibromatosis type 1 and symptomatic plexiform neurofibromas that are not amenable to complete resection.

Approval for this agent was based on overall response rate findings from a multicenter, single-arm, phase 2b trial. The trial, which enrolled 58 adults and 56 pediatric patients with this rare disease, reported confirmed overall response rates of 41% among adults and 52% among children.

Adverse reactions occurring in at least 25% of adults included rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. Mirdametinib can also cause ocular toxicity. Treatment should be withheld, discontinued, or the dosage reduced based on the severity of these adverse reactions, according to the FDA notice.

2. The FDA has approved vimseltinib (Romvimza, Deciphera Pharmaceuticals, LLC) to treat adult patients with symptomatic tenosynovial giant cell tumors who will not benefit from surgical resection.

Vimseltinib was approved based on findings from the MOTION trial, which included 123 patients randomly assigned 2:1 to vimseltinib 30 mg twice weekly or to placebo for 24 weeks. At 25 weeks, the objective response rate was 40% in the vimseltinib arm and 0% in the placebo arm. The median duration of response was not reached in the vimseltinib arm. Patients receiving vimseltinib also demonstrated significant improvements in active range of motion, physical functioning, and pain at this time. After another 6 months of follow-up, 58% of responders had a duration of response of 9 months or longer.

Treatment-emergent adverse events in MOTION were largely of grade 1 or 2. The most common adverse reactions, occurring in at least 20% of patients, included increased aspartate aminotransferase, periorbital edema, fatigue, rash, and cholesterol.

 

New or Expanded Indications

1. The FDA has approved a supplemental Biologics License Application for brentuximab vedotin (Adcetris, Seagen Inc.), in combination with lenalidomide and rituximab, for adults with relapsed or refractory large B-cell lymphoma, after at least two prior lines of therapy, who are ineligible for stem cell transplant or chimeric antigen receptor T-cell therapy. This includes patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma.

Approval was based on the randomized, double-blind, placebo-controlled ECHELON-3 trial, which randomly assigned patients 1:1 to receive lenalidomide and rituximab plus either brentuximab vedotin or placebo until disease progression or unacceptable toxicity. Researchers reported a median overall survival of 13.8 months in the treatment group vs 8.5 months in the placebo group (hazard ratio, 0.63).

2. The FDA has approved the Biologics License Application for Ospomyv and Xbryk (Samsung Bioepis Co.) — biosimilars referencing denosumab (Prolia and Xgeva, respectively) — to treat osteoporosis and cancer-related bone loss.

Ospomyv and Xbryk have been approved for use in all indications of the approved reference drugs. Specifically, Xbryk is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors or multiple myeloma, and Ospomyv is indicated in several populations of patients with osteoporosis at high risk for fracture.

“The FDA approval of Ospomyv and Xbryk marks a key step in improving patient access and alleviating treatment cost for patients with osteoporosis and cancer-related bone loss in the United States,” Byoungin Jung, vice president at Samsung Bioepis, said in the news release.

 

Drug Commercialization Halt

Pfizer announced last month that it will halt the global development and commercialization of its hemophilia gene therapy fidanacogene elaparvovec (Beqvez). The company cited several reasons for the discontinuation, including low demand from patients and doctors.

Beqvez is a one-time therapy approved in the United States last April to treat adults with moderate to severe hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 men in the United States.

The significant price tag is one reason hematologists have cited for the low uptake. Another barrier is that “we don’t know the long-term outcomes” associated with the drug, pediatric hematologist Ben Samelson-Jones, MD, PhD, of the Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia, Philadelphia, told this news organization earlier this year.

Other issues include the prospect of newer treatment advances in the hemophilia space and logistical challenges. “There’s just a lot of logistics to getting an institution ready to provide this type of therapy,” Samelson-Jones added.

A version of this article first appeared on Medscape.com.

Last month, the United States Food and Drug Administration (FDA) approved two new drugs and two biosimilars as well as halted commercialization for a hemophilia treatment.

Here’s a deeper look of what happened last month.

 

New Drugs

1. The FDA has approved mirdametinib (Gomekli, SpringWorks Therapeutics, Inc.) for adult and pediatric patients 2 years or older with neurofibromatosis type 1 and symptomatic plexiform neurofibromas that are not amenable to complete resection.

Approval for this agent was based on overall response rate findings from a multicenter, single-arm, phase 2b trial. The trial, which enrolled 58 adults and 56 pediatric patients with this rare disease, reported confirmed overall response rates of 41% among adults and 52% among children.

Adverse reactions occurring in at least 25% of adults included rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. Mirdametinib can also cause ocular toxicity. Treatment should be withheld, discontinued, or the dosage reduced based on the severity of these adverse reactions, according to the FDA notice.

2. The FDA has approved vimseltinib (Romvimza, Deciphera Pharmaceuticals, LLC) to treat adult patients with symptomatic tenosynovial giant cell tumors who will not benefit from surgical resection.

Vimseltinib was approved based on findings from the MOTION trial, which included 123 patients randomly assigned 2:1 to vimseltinib 30 mg twice weekly or to placebo for 24 weeks. At 25 weeks, the objective response rate was 40% in the vimseltinib arm and 0% in the placebo arm. The median duration of response was not reached in the vimseltinib arm. Patients receiving vimseltinib also demonstrated significant improvements in active range of motion, physical functioning, and pain at this time. After another 6 months of follow-up, 58% of responders had a duration of response of 9 months or longer.

Treatment-emergent adverse events in MOTION were largely of grade 1 or 2. The most common adverse reactions, occurring in at least 20% of patients, included increased aspartate aminotransferase, periorbital edema, fatigue, rash, and cholesterol.

 

New or Expanded Indications

1. The FDA has approved a supplemental Biologics License Application for brentuximab vedotin (Adcetris, Seagen Inc.), in combination with lenalidomide and rituximab, for adults with relapsed or refractory large B-cell lymphoma, after at least two prior lines of therapy, who are ineligible for stem cell transplant or chimeric antigen receptor T-cell therapy. This includes patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma.

Approval was based on the randomized, double-blind, placebo-controlled ECHELON-3 trial, which randomly assigned patients 1:1 to receive lenalidomide and rituximab plus either brentuximab vedotin or placebo until disease progression or unacceptable toxicity. Researchers reported a median overall survival of 13.8 months in the treatment group vs 8.5 months in the placebo group (hazard ratio, 0.63).

2. The FDA has approved the Biologics License Application for Ospomyv and Xbryk (Samsung Bioepis Co.) — biosimilars referencing denosumab (Prolia and Xgeva, respectively) — to treat osteoporosis and cancer-related bone loss.

Ospomyv and Xbryk have been approved for use in all indications of the approved reference drugs. Specifically, Xbryk is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors or multiple myeloma, and Ospomyv is indicated in several populations of patients with osteoporosis at high risk for fracture.

“The FDA approval of Ospomyv and Xbryk marks a key step in improving patient access and alleviating treatment cost for patients with osteoporosis and cancer-related bone loss in the United States,” Byoungin Jung, vice president at Samsung Bioepis, said in the news release.

 

Drug Commercialization Halt

Pfizer announced last month that it will halt the global development and commercialization of its hemophilia gene therapy fidanacogene elaparvovec (Beqvez). The company cited several reasons for the discontinuation, including low demand from patients and doctors.

Beqvez is a one-time therapy approved in the United States last April to treat adults with moderate to severe hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 men in the United States.

The significant price tag is one reason hematologists have cited for the low uptake. Another barrier is that “we don’t know the long-term outcomes” associated with the drug, pediatric hematologist Ben Samelson-Jones, MD, PhD, of the Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia, Philadelphia, told this news organization earlier this year.

Other issues include the prospect of newer treatment advances in the hemophilia space and logistical challenges. “There’s just a lot of logistics to getting an institution ready to provide this type of therapy,” Samelson-Jones added.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with stage I non–small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) have a low rate of acute toxicities and 90-day mortality, according to a recent study evaluating real-world patient outcomes.

METHODOLOGY:

• SBRT is generally considered a safe treatment option in patients with stage I NSCLC who have medically inoperable tumors or who refuse surgery. Although rare, clinically relevant acute toxicities or early mortality can occur.
• In the current real-world analysis, researchers explored toxicity and 90-day mortality outcomes in patients who received SBRT to develop a better understanding of how often they happen and whether certain patients are at higher risk.
• Researchers analyzed data from the Dutch Lung Cancer Audit for Radiotherapy database, which included 7279 patients with stage I NSCLC who received SBRT between January 2017 and December 2021.
• Participants had a mean age of 72.5 years; 21.6% were older than 80 years. Over half were men (50.7%), most (73.3%) had WHO scores of 0-1, and about two thirds (64.6%) had cT1a-b tumors, mostly in the upper lobes (65.2%).
• Prediction models for acute toxicity and 90-day mortality were developed and internally validated using logistic regression analysis. Acute toxicity was defined as grade 2 or higher radiation pneumonitis or grade 3 or higher non-hematologic toxicity within 90 days after SBRT. The 90-day mortality was defined as mortality from any cause within 90 days after SBRT.

TAKEAWAY:

• Acute toxicity was observed in 3.8% patients, with more common types including dyspnea (1.8%), radiation pneumonitis (1.2%), fatigue (0.3%), and dysphagia (0.2%).
• Predictors for acute toxicity included WHO performance status of 2 or higher (adjusted odds ratio [aOR], 1.89; P = .003), middle or lower lobe tumor location (aOR, 1.38), cT1c-cT2a stage (aOR, 1.66), as well as lower forced expiratory volume in 1 second and higher mean lung dose.
• Overall, 90-day mortality was observed in 1.7% patients, with predictors including male sex, WHO performance status of 2 or higher (aOR, 6.11; P < .001), and acute toxicity (aOR, 8.89; P < .001).
• Advanced age was not associated with a higher risk for acute toxicity or 90-day mortality.

IN PRACTICE:

“This real-world study confirms that clinically relevant acute toxicity after lung SBRT for stage I NSCLC is rare,” and the 90-day mortality rate is low, the authors wrote. “Although these findings could inform clinical practice and enable individualized risk estimations, these parameters (and the others in the presented nomograms) should not serve as contraindication for SBRT as the benefits in terms of local control and survival outweigh the risks in most patients.”

SOURCE:

This study, led by Peter S.N. van Rossum, MD, PhD, Amsterdam UMC in Amsterdam, the Netherlands, was published online in Journal of Thoracic Oncology.

LIMITATIONS:

Patients with ultracentral tumor locations were excluded, which may have limited the generalizability of the findings. The Dutch Lung Cancer Audit for Radiotherapy database does not register whether a patient has interstitial lung disease or whether the treated tumor is at a central location, which carry increased risks for toxicity. The findings may not be applicable to patients receiving combined immunotherapy and SBRT, as this combination was not included in the current analysis. External validation of the prediction models is needed for application outside the Netherlands.

DISCLOSURES:

The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with stage I non–small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) have a low rate of acute toxicities and 90-day mortality, according to a recent study evaluating real-world patient outcomes.

METHODOLOGY:

• SBRT is generally considered a safe treatment option in patients with stage I NSCLC who have medically inoperable tumors or who refuse surgery. Although rare, clinically relevant acute toxicities or early mortality can occur.
• In the current real-world analysis, researchers explored toxicity and 90-day mortality outcomes in patients who received SBRT to develop a better understanding of how often they happen and whether certain patients are at higher risk.
• Researchers analyzed data from the Dutch Lung Cancer Audit for Radiotherapy database, which included 7279 patients with stage I NSCLC who received SBRT between January 2017 and December 2021.
• Participants had a mean age of 72.5 years; 21.6% were older than 80 years. Over half were men (50.7%), most (73.3%) had WHO scores of 0-1, and about two thirds (64.6%) had cT1a-b tumors, mostly in the upper lobes (65.2%).
• Prediction models for acute toxicity and 90-day mortality were developed and internally validated using logistic regression analysis. Acute toxicity was defined as grade 2 or higher radiation pneumonitis or grade 3 or higher non-hematologic toxicity within 90 days after SBRT. The 90-day mortality was defined as mortality from any cause within 90 days after SBRT.

TAKEAWAY:

• Acute toxicity was observed in 3.8% patients, with more common types including dyspnea (1.8%), radiation pneumonitis (1.2%), fatigue (0.3%), and dysphagia (0.2%).
• Predictors for acute toxicity included WHO performance status of 2 or higher (adjusted odds ratio [aOR], 1.89; P = .003), middle or lower lobe tumor location (aOR, 1.38), cT1c-cT2a stage (aOR, 1.66), as well as lower forced expiratory volume in 1 second and higher mean lung dose.
• Overall, 90-day mortality was observed in 1.7% patients, with predictors including male sex, WHO performance status of 2 or higher (aOR, 6.11; P < .001), and acute toxicity (aOR, 8.89; P < .001).
• Advanced age was not associated with a higher risk for acute toxicity or 90-day mortality.

IN PRACTICE:

“This real-world study confirms that clinically relevant acute toxicity after lung SBRT for stage I NSCLC is rare,” and the 90-day mortality rate is low, the authors wrote. “Although these findings could inform clinical practice and enable individualized risk estimations, these parameters (and the others in the presented nomograms) should not serve as contraindication for SBRT as the benefits in terms of local control and survival outweigh the risks in most patients.”

SOURCE:

This study, led by Peter S.N. van Rossum, MD, PhD, Amsterdam UMC in Amsterdam, the Netherlands, was published online in Journal of Thoracic Oncology.

LIMITATIONS:

Patients with ultracentral tumor locations were excluded, which may have limited the generalizability of the findings. The Dutch Lung Cancer Audit for Radiotherapy database does not register whether a patient has interstitial lung disease or whether the treated tumor is at a central location, which carry increased risks for toxicity. The findings may not be applicable to patients receiving combined immunotherapy and SBRT, as this combination was not included in the current analysis. External validation of the prediction models is needed for application outside the Netherlands.

DISCLOSURES:

The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with stage I non–small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) have a low rate of acute toxicities and 90-day mortality, according to a recent study evaluating real-world patient outcomes.

METHODOLOGY:

• SBRT is generally considered a safe treatment option in patients with stage I NSCLC who have medically inoperable tumors or who refuse surgery. Although rare, clinically relevant acute toxicities or early mortality can occur.
• In the current real-world analysis, researchers explored toxicity and 90-day mortality outcomes in patients who received SBRT to develop a better understanding of how often they happen and whether certain patients are at higher risk.
• Researchers analyzed data from the Dutch Lung Cancer Audit for Radiotherapy database, which included 7279 patients with stage I NSCLC who received SBRT between January 2017 and December 2021.
• Participants had a mean age of 72.5 years; 21.6% were older than 80 years. Over half were men (50.7%), most (73.3%) had WHO scores of 0-1, and about two thirds (64.6%) had cT1a-b tumors, mostly in the upper lobes (65.2%).
• Prediction models for acute toxicity and 90-day mortality were developed and internally validated using logistic regression analysis. Acute toxicity was defined as grade 2 or higher radiation pneumonitis or grade 3 or higher non-hematologic toxicity within 90 days after SBRT. The 90-day mortality was defined as mortality from any cause within 90 days after SBRT.

TAKEAWAY:

• Acute toxicity was observed in 3.8% patients, with more common types including dyspnea (1.8%), radiation pneumonitis (1.2%), fatigue (0.3%), and dysphagia (0.2%).
• Predictors for acute toxicity included WHO performance status of 2 or higher (adjusted odds ratio [aOR], 1.89; P = .003), middle or lower lobe tumor location (aOR, 1.38), cT1c-cT2a stage (aOR, 1.66), as well as lower forced expiratory volume in 1 second and higher mean lung dose.
• Overall, 90-day mortality was observed in 1.7% patients, with predictors including male sex, WHO performance status of 2 or higher (aOR, 6.11; P < .001), and acute toxicity (aOR, 8.89; P < .001).
• Advanced age was not associated with a higher risk for acute toxicity or 90-day mortality.

IN PRACTICE:

“This real-world study confirms that clinically relevant acute toxicity after lung SBRT for stage I NSCLC is rare,” and the 90-day mortality rate is low, the authors wrote. “Although these findings could inform clinical practice and enable individualized risk estimations, these parameters (and the others in the presented nomograms) should not serve as contraindication for SBRT as the benefits in terms of local control and survival outweigh the risks in most patients.”

SOURCE:

This study, led by Peter S.N. van Rossum, MD, PhD, Amsterdam UMC in Amsterdam, the Netherlands, was published online in Journal of Thoracic Oncology.

LIMITATIONS:

Patients with ultracentral tumor locations were excluded, which may have limited the generalizability of the findings. The Dutch Lung Cancer Audit for Radiotherapy database does not register whether a patient has interstitial lung disease or whether the treated tumor is at a central location, which carry increased risks for toxicity. The findings may not be applicable to patients receiving combined immunotherapy and SBRT, as this combination was not included in the current analysis. External validation of the prediction models is needed for application outside the Netherlands.

DISCLOSURES:

The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has declined to approve linvoseltamab (Regeneron), a bispecific antibody being evaluated to treat relapsed/refractory multiple myeloma after progression on at least three previous therapies.

On August 20, Regeneron announced that it had received a complete response letter from the FDA regarding its Biologics License Application for linvoseltamab, citing issues at a third-party manufacturer.

More specifically, Regeneron said in a company press release that the FDA issued the complete response letter based on findings from “a preapproval inspection at a third-party fill/finish manufacturer for another company’s product candidate.”

The third-party manufacturer told Regeneron it believes that the issues have been resolved, Regeneron said, and that facility is now awaiting a follow-up FDA inspection in the “coming months.”

Regeneron noted that this “anticipated outcome” from the FDA preapproval inspection had been disclosed previously during a company earnings call on August 1.

On that call, Regeneron had discussed the FDA’s concerns about the third-party manufacturer and anticipated that “any potential FDA approval for linvoseltamab is likely to be delayed beyond the August 22 PDUFA date.”

Regeneron had initially filed a Biologics License Application for its bispecific antibody in 2023, based on findings from the phase 1/2 single arm LINKER-MM1 trial. 

In the latest published trial findings, investigators reported that, at a median follow-up of about 14 months, 71% of the 117 patients receiving 200 mg of linvoseltamab achieved an overall response, with 50% achieving a complete response. The probability of survival at 12 months was 75.3%.

This would have been the first approval for linvoseltamab, which would have joined two agents already on the US market for relapsed/refractory multiple myeloma: teclistamab (Tecvayli, Janssen) and elranatamab (Elrexfio, Pfizer).

Pricing information for linvoseltamab is not yet available, but its competitors teclistamab and elranatamab are reported to cost around $40,000 per month.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has declined to approve linvoseltamab (Regeneron), a bispecific antibody being evaluated to treat relapsed/refractory multiple myeloma after progression on at least three previous therapies.

On August 20, Regeneron announced that it had received a complete response letter from the FDA regarding its Biologics License Application for linvoseltamab, citing issues at a third-party manufacturer.

More specifically, Regeneron said in a company press release that the FDA issued the complete response letter based on findings from “a preapproval inspection at a third-party fill/finish manufacturer for another company’s product candidate.”

The third-party manufacturer told Regeneron it believes that the issues have been resolved, Regeneron said, and that facility is now awaiting a follow-up FDA inspection in the “coming months.”

Regeneron noted that this “anticipated outcome” from the FDA preapproval inspection had been disclosed previously during a company earnings call on August 1.

On that call, Regeneron had discussed the FDA’s concerns about the third-party manufacturer and anticipated that “any potential FDA approval for linvoseltamab is likely to be delayed beyond the August 22 PDUFA date.”

Regeneron had initially filed a Biologics License Application for its bispecific antibody in 2023, based on findings from the phase 1/2 single arm LINKER-MM1 trial. 

In the latest published trial findings, investigators reported that, at a median follow-up of about 14 months, 71% of the 117 patients receiving 200 mg of linvoseltamab achieved an overall response, with 50% achieving a complete response. The probability of survival at 12 months was 75.3%.

This would have been the first approval for linvoseltamab, which would have joined two agents already on the US market for relapsed/refractory multiple myeloma: teclistamab (Tecvayli, Janssen) and elranatamab (Elrexfio, Pfizer).

Pricing information for linvoseltamab is not yet available, but its competitors teclistamab and elranatamab are reported to cost around $40,000 per month.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has declined to approve linvoseltamab (Regeneron), a bispecific antibody being evaluated to treat relapsed/refractory multiple myeloma after progression on at least three previous therapies.

On August 20, Regeneron announced that it had received a complete response letter from the FDA regarding its Biologics License Application for linvoseltamab, citing issues at a third-party manufacturer.

More specifically, Regeneron said in a company press release that the FDA issued the complete response letter based on findings from “a preapproval inspection at a third-party fill/finish manufacturer for another company’s product candidate.”

The third-party manufacturer told Regeneron it believes that the issues have been resolved, Regeneron said, and that facility is now awaiting a follow-up FDA inspection in the “coming months.”

Regeneron noted that this “anticipated outcome” from the FDA preapproval inspection had been disclosed previously during a company earnings call on August 1.

On that call, Regeneron had discussed the FDA’s concerns about the third-party manufacturer and anticipated that “any potential FDA approval for linvoseltamab is likely to be delayed beyond the August 22 PDUFA date.”

Regeneron had initially filed a Biologics License Application for its bispecific antibody in 2023, based on findings from the phase 1/2 single arm LINKER-MM1 trial. 

In the latest published trial findings, investigators reported that, at a median follow-up of about 14 months, 71% of the 117 patients receiving 200 mg of linvoseltamab achieved an overall response, with 50% achieving a complete response. The probability of survival at 12 months was 75.3%.

This would have been the first approval for linvoseltamab, which would have joined two agents already on the US market for relapsed/refractory multiple myeloma: teclistamab (Tecvayli, Janssen) and elranatamab (Elrexfio, Pfizer).

Pricing information for linvoseltamab is not yet available, but its competitors teclistamab and elranatamab are reported to cost around $40,000 per month.
 

A version of this article appeared on Medscape.com.

TOPLINE:

GPT-4 generated highly accurate pancreatic cancer synoptic reports from original reports, outperforming GPT-3.5. Using GPT-4 reports instead of original reports, surgeons were able to better assess tumor resectability in patients with pancreatic ductal adenocarcinoma and saved time evaluating reports.

METHODOLOGY:

• Compared with original reports, structured imaging reports help surgeons assess tumor resectability in patients with pancreatic ductal adenocarcinoma. However, radiologist uptake of structured reporting remains inconsistent.
• To determine whether converting free-text (ie, original) radiology reports into structured reports can benefit surgeons, researchers evaluated how well GPT-4 and GPT-3.5 were able to generate pancreatic ductal adenocarcinoma synoptic reports from originals.
• The retrospective study included 180 consecutive pancreatic ductal adenocarcinoma staging CT reports, which were reviewed by two radiologists to establish a reference standard for 14 key findings and National Comprehensive Cancer Network resectability category.
• Researchers prompted GPT-3.5 and GPT-4 to create synoptic reports from original reports using the same criteria, and surgeons compared the precision, accuracy, and time to assess the original and artificial intelligence (AI)–generated reports.

TAKEAWAY:

• GPT-4 outperformed GPT-3.5 on all metrics evaluated. For instance, compared with GPT-3.5, GPT-4 achieved equal or higher F1 scores for all 14 key features (F1 scores help assess the precision and recall of a machine-learning model).
• GPT-4 also demonstrated greater precision than GPT-3.5 for extracting superior mesenteric artery involvement (100% vs 88.8%, respectively) and for categorizing resectability.
• Compared with original reports, AI-generated reports helped surgeons better categorize resectability (83% vs 76%, respectively; P = .03), and surgeons spent less time when using AI-generated reports.
• The AI-generated reports did lead to some clinically notable errors. GPT-4, for instance, made errors in extracting common hepatic artery involvement.

IN PRACTICE:

“In our study, GPT-4 was near-perfect at automatically creating pancreatic ductal adenocarcinoma synoptic reports from original reports, outperforming GPT-3.5 overall,” the authors wrote. This “represents a useful application that can increase standardization and improve communication between radiologists and surgeons.” However, the authors cautioned, the “presence of some clinically significant errors highlights the need for implementation in supervised and preliminary contexts, rather than being relied on for management decisions.” 

SOURCE:

The study, with first author Rajesh Bhayana, MD, University Health Network in Toronto, Ontario, Canada, was published online in Radiology. 

LIMITATIONS:

While GPT-4 showed high accuracy in report generation, it did lead to some errors. Researchers also relied on original reports when generating the AI reports, and the original reports can contain ambiguous descriptions and language.

DISCLOSURES:

Dr. Bhayana reported no relevant conflicts of interest. Additional disclosures are noted in the original article.

A version of this article first appeared on Medscape.com.

TOPLINE:

GPT-4 generated highly accurate pancreatic cancer synoptic reports from original reports, outperforming GPT-3.5. Using GPT-4 reports instead of original reports, surgeons were able to better assess tumor resectability in patients with pancreatic ductal adenocarcinoma and saved time evaluating reports.

METHODOLOGY:

• Compared with original reports, structured imaging reports help surgeons assess tumor resectability in patients with pancreatic ductal adenocarcinoma. However, radiologist uptake of structured reporting remains inconsistent.
• To determine whether converting free-text (ie, original) radiology reports into structured reports can benefit surgeons, researchers evaluated how well GPT-4 and GPT-3.5 were able to generate pancreatic ductal adenocarcinoma synoptic reports from originals.
• The retrospective study included 180 consecutive pancreatic ductal adenocarcinoma staging CT reports, which were reviewed by two radiologists to establish a reference standard for 14 key findings and National Comprehensive Cancer Network resectability category.
• Researchers prompted GPT-3.5 and GPT-4 to create synoptic reports from original reports using the same criteria, and surgeons compared the precision, accuracy, and time to assess the original and artificial intelligence (AI)–generated reports.

TAKEAWAY:

• GPT-4 outperformed GPT-3.5 on all metrics evaluated. For instance, compared with GPT-3.5, GPT-4 achieved equal or higher F1 scores for all 14 key features (F1 scores help assess the precision and recall of a machine-learning model).
• GPT-4 also demonstrated greater precision than GPT-3.5 for extracting superior mesenteric artery involvement (100% vs 88.8%, respectively) and for categorizing resectability.
• Compared with original reports, AI-generated reports helped surgeons better categorize resectability (83% vs 76%, respectively; P = .03), and surgeons spent less time when using AI-generated reports.
• The AI-generated reports did lead to some clinically notable errors. GPT-4, for instance, made errors in extracting common hepatic artery involvement.

IN PRACTICE:

“In our study, GPT-4 was near-perfect at automatically creating pancreatic ductal adenocarcinoma synoptic reports from original reports, outperforming GPT-3.5 overall,” the authors wrote. This “represents a useful application that can increase standardization and improve communication between radiologists and surgeons.” However, the authors cautioned, the “presence of some clinically significant errors highlights the need for implementation in supervised and preliminary contexts, rather than being relied on for management decisions.” 

SOURCE:

The study, with first author Rajesh Bhayana, MD, University Health Network in Toronto, Ontario, Canada, was published online in Radiology. 

LIMITATIONS:

While GPT-4 showed high accuracy in report generation, it did lead to some errors. Researchers also relied on original reports when generating the AI reports, and the original reports can contain ambiguous descriptions and language.

DISCLOSURES:

Dr. Bhayana reported no relevant conflicts of interest. Additional disclosures are noted in the original article.

A version of this article first appeared on Medscape.com.

TOPLINE:

GPT-4 generated highly accurate pancreatic cancer synoptic reports from original reports, outperforming GPT-3.5. Using GPT-4 reports instead of original reports, surgeons were able to better assess tumor resectability in patients with pancreatic ductal adenocarcinoma and saved time evaluating reports.

METHODOLOGY:

• Compared with original reports, structured imaging reports help surgeons assess tumor resectability in patients with pancreatic ductal adenocarcinoma. However, radiologist uptake of structured reporting remains inconsistent.
• To determine whether converting free-text (ie, original) radiology reports into structured reports can benefit surgeons, researchers evaluated how well GPT-4 and GPT-3.5 were able to generate pancreatic ductal adenocarcinoma synoptic reports from originals.
• The retrospective study included 180 consecutive pancreatic ductal adenocarcinoma staging CT reports, which were reviewed by two radiologists to establish a reference standard for 14 key findings and National Comprehensive Cancer Network resectability category.
• Researchers prompted GPT-3.5 and GPT-4 to create synoptic reports from original reports using the same criteria, and surgeons compared the precision, accuracy, and time to assess the original and artificial intelligence (AI)–generated reports.

TAKEAWAY:

• GPT-4 outperformed GPT-3.5 on all metrics evaluated. For instance, compared with GPT-3.5, GPT-4 achieved equal or higher F1 scores for all 14 key features (F1 scores help assess the precision and recall of a machine-learning model).
• GPT-4 also demonstrated greater precision than GPT-3.5 for extracting superior mesenteric artery involvement (100% vs 88.8%, respectively) and for categorizing resectability.
• Compared with original reports, AI-generated reports helped surgeons better categorize resectability (83% vs 76%, respectively; P = .03), and surgeons spent less time when using AI-generated reports.
• The AI-generated reports did lead to some clinically notable errors. GPT-4, for instance, made errors in extracting common hepatic artery involvement.

IN PRACTICE:

“In our study, GPT-4 was near-perfect at automatically creating pancreatic ductal adenocarcinoma synoptic reports from original reports, outperforming GPT-3.5 overall,” the authors wrote. This “represents a useful application that can increase standardization and improve communication between radiologists and surgeons.” However, the authors cautioned, the “presence of some clinically significant errors highlights the need for implementation in supervised and preliminary contexts, rather than being relied on for management decisions.” 

SOURCE:

The study, with first author Rajesh Bhayana, MD, University Health Network in Toronto, Ontario, Canada, was published online in Radiology. 

LIMITATIONS:

While GPT-4 showed high accuracy in report generation, it did lead to some errors. Researchers also relied on original reports when generating the AI reports, and the original reports can contain ambiguous descriptions and language.

DISCLOSURES:

Dr. Bhayana reported no relevant conflicts of interest. Additional disclosures are noted in the original article.

A version of this article first appeared on Medscape.com.

Mark Lewis, MD, saw the pain in his patient’s body. The man’s gastrointestinal tumor had metastasized to his bones. Even breathing had become agonizing.

It was a Friday afternoon. Dr. Lewis could see his patient would struggle to make it through the weekend without some pain relief.

When this happens, “the clock is ticking,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Health in Salt Lake City, Utah. “A patient, especially one with more advanced disease, only has so much time to wait for care.”

Dr. Lewis sent in an electronic request for an opioid prescription to help ease his patient’s pain through the weekend. Once the prescription had gone through, Dr. Lewis told his patient the medication should be ready to pick up at his local pharmacy.

Dr. Lewis left work that Friday feeling a little lighter, knowing the pain medication would help his patient over the weekend.

Moments after walking into the clinic on Monday morning, Dr. Lewis received an unexpected message: “Your patient is in the hospital.”

The events of the weekend soon unfolded.

Dr. Lewis learned that when his patient went to the pharmacy to pick up his pain medication, the pharmacist told him the prescription required prior authorization.

The patient left the pharmacy empty-handed. Hours later, he was in the emergency room (ER) in extreme pain — the exact situation Dr. Lewis had been trying to avoid.

Dr. Lewis felt a sense of powerlessness in that moment.

“I had been left in the dark,” he said. The oncologist-patient relationship is predicated on trust and “that trust is eroded when I can’t give my patients the care they need,” he explained. “I can’t stand overpromising and underdelivering to them.”

Dr. Lewis had received no communication from the insurer that the prescription required prior authorization, no red flag that the request had been denied, and no notification to call the insurer.

Although physicians may need to tread carefully when prescribing opioids over the long term, “this was simply a prescription for 2-3 days of opioids for the exact patient who the drugs were developed to benefit,” Dr. Lewis said. But instead, “he ended up in ER with a pain crisis.”

Prior authorization delays like this often mean patients pay the price.

“These delays are not trivial,” Dr. Lewis said.

A recent study, presented at the ASCO Quality Care Symposium in October, found that among 3304 supportive care prescriptions requiring prior authorization, insurance companies denied 8% of requests, with final denials taking as long as 78 days. Among approved prescriptions, about 40% happened on the same day, while the remaining took anywhere from 1 to 54 days.

Denying or delaying necessary and cost-effective care, even briefly, can harm patients and lead to higher costs. A 2022 survey from the American Medical Association found that instead of reducing low-value care as insurance companies claim, prior authorization often leads to higher overall use of healthcare resources. More specifically, almost half of physicians surveyed said that prior authorization led to an ER visit or need for immediate care.

In this patient’s case, filling the opioid prescription that Friday would have cost no more than $300, possibly as little as $30. The ER visit to manage the patient’s pain crisis costs thousands.

The major issue overall, Dr. Lewis said, is the disconnect between the time spent waiting for prior authorization approvals and the necessity of these treatments. Dr. Lewis says even standard chemotherapy often requires prior authorization.

“The currency we all share is time,” Dr. Lewis said. “But it often feels like there’s very little urgency on insurance company side to approve a treatment, which places a heavy weight on patients and physicians.”

“It just shouldn’t be this hard,” he said.

A version of this article appeared on Medscape.com as part of the Gatekeepers of Care series on issues oncologists and people with cancer face navigating health insurance company requirements. Read more about the series here. Please email vstern@medscape.net to share experiences with prior authorization or other challenges receiving care.

Mark Lewis, MD, saw the pain in his patient’s body. The man’s gastrointestinal tumor had metastasized to his bones. Even breathing had become agonizing.

It was a Friday afternoon. Dr. Lewis could see his patient would struggle to make it through the weekend without some pain relief.

When this happens, “the clock is ticking,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Health in Salt Lake City, Utah. “A patient, especially one with more advanced disease, only has so much time to wait for care.”

Dr. Lewis sent in an electronic request for an opioid prescription to help ease his patient’s pain through the weekend. Once the prescription had gone through, Dr. Lewis told his patient the medication should be ready to pick up at his local pharmacy.

Dr. Lewis left work that Friday feeling a little lighter, knowing the pain medication would help his patient over the weekend.

Moments after walking into the clinic on Monday morning, Dr. Lewis received an unexpected message: “Your patient is in the hospital.”

The events of the weekend soon unfolded.

Dr. Lewis learned that when his patient went to the pharmacy to pick up his pain medication, the pharmacist told him the prescription required prior authorization.

The patient left the pharmacy empty-handed. Hours later, he was in the emergency room (ER) in extreme pain — the exact situation Dr. Lewis had been trying to avoid.

Dr. Lewis felt a sense of powerlessness in that moment.

“I had been left in the dark,” he said. The oncologist-patient relationship is predicated on trust and “that trust is eroded when I can’t give my patients the care they need,” he explained. “I can’t stand overpromising and underdelivering to them.”

Dr. Lewis had received no communication from the insurer that the prescription required prior authorization, no red flag that the request had been denied, and no notification to call the insurer.

Although physicians may need to tread carefully when prescribing opioids over the long term, “this was simply a prescription for 2-3 days of opioids for the exact patient who the drugs were developed to benefit,” Dr. Lewis said. But instead, “he ended up in ER with a pain crisis.”

Prior authorization delays like this often mean patients pay the price.

“These delays are not trivial,” Dr. Lewis said.

A recent study, presented at the ASCO Quality Care Symposium in October, found that among 3304 supportive care prescriptions requiring prior authorization, insurance companies denied 8% of requests, with final denials taking as long as 78 days. Among approved prescriptions, about 40% happened on the same day, while the remaining took anywhere from 1 to 54 days.

Denying or delaying necessary and cost-effective care, even briefly, can harm patients and lead to higher costs. A 2022 survey from the American Medical Association found that instead of reducing low-value care as insurance companies claim, prior authorization often leads to higher overall use of healthcare resources. More specifically, almost half of physicians surveyed said that prior authorization led to an ER visit or need for immediate care.

In this patient’s case, filling the opioid prescription that Friday would have cost no more than $300, possibly as little as $30. The ER visit to manage the patient’s pain crisis costs thousands.

The major issue overall, Dr. Lewis said, is the disconnect between the time spent waiting for prior authorization approvals and the necessity of these treatments. Dr. Lewis says even standard chemotherapy often requires prior authorization.

“The currency we all share is time,” Dr. Lewis said. “But it often feels like there’s very little urgency on insurance company side to approve a treatment, which places a heavy weight on patients and physicians.”

“It just shouldn’t be this hard,” he said.

A version of this article appeared on Medscape.com as part of the Gatekeepers of Care series on issues oncologists and people with cancer face navigating health insurance company requirements. Read more about the series here. Please email vstern@medscape.net to share experiences with prior authorization or other challenges receiving care.

Mark Lewis, MD, saw the pain in his patient’s body. The man’s gastrointestinal tumor had metastasized to his bones. Even breathing had become agonizing.

It was a Friday afternoon. Dr. Lewis could see his patient would struggle to make it through the weekend without some pain relief.

When this happens, “the clock is ticking,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Health in Salt Lake City, Utah. “A patient, especially one with more advanced disease, only has so much time to wait for care.”

Dr. Lewis sent in an electronic request for an opioid prescription to help ease his patient’s pain through the weekend. Once the prescription had gone through, Dr. Lewis told his patient the medication should be ready to pick up at his local pharmacy.

Dr. Lewis left work that Friday feeling a little lighter, knowing the pain medication would help his patient over the weekend.

Moments after walking into the clinic on Monday morning, Dr. Lewis received an unexpected message: “Your patient is in the hospital.”

The events of the weekend soon unfolded.

Dr. Lewis learned that when his patient went to the pharmacy to pick up his pain medication, the pharmacist told him the prescription required prior authorization.

The patient left the pharmacy empty-handed. Hours later, he was in the emergency room (ER) in extreme pain — the exact situation Dr. Lewis had been trying to avoid.

Dr. Lewis felt a sense of powerlessness in that moment.

“I had been left in the dark,” he said. The oncologist-patient relationship is predicated on trust and “that trust is eroded when I can’t give my patients the care they need,” he explained. “I can’t stand overpromising and underdelivering to them.”

Dr. Lewis had received no communication from the insurer that the prescription required prior authorization, no red flag that the request had been denied, and no notification to call the insurer.

Although physicians may need to tread carefully when prescribing opioids over the long term, “this was simply a prescription for 2-3 days of opioids for the exact patient who the drugs were developed to benefit,” Dr. Lewis said. But instead, “he ended up in ER with a pain crisis.”

Prior authorization delays like this often mean patients pay the price.

“These delays are not trivial,” Dr. Lewis said.

A recent study, presented at the ASCO Quality Care Symposium in October, found that among 3304 supportive care prescriptions requiring prior authorization, insurance companies denied 8% of requests, with final denials taking as long as 78 days. Among approved prescriptions, about 40% happened on the same day, while the remaining took anywhere from 1 to 54 days.

Denying or delaying necessary and cost-effective care, even briefly, can harm patients and lead to higher costs. A 2022 survey from the American Medical Association found that instead of reducing low-value care as insurance companies claim, prior authorization often leads to higher overall use of healthcare resources. More specifically, almost half of physicians surveyed said that prior authorization led to an ER visit or need for immediate care.

In this patient’s case, filling the opioid prescription that Friday would have cost no more than $300, possibly as little as $30. The ER visit to manage the patient’s pain crisis costs thousands.

The major issue overall, Dr. Lewis said, is the disconnect between the time spent waiting for prior authorization approvals and the necessity of these treatments. Dr. Lewis says even standard chemotherapy often requires prior authorization.

“The currency we all share is time,” Dr. Lewis said. “But it often feels like there’s very little urgency on insurance company side to approve a treatment, which places a heavy weight on patients and physicians.”

“It just shouldn’t be this hard,” he said.

A version of this article appeared on Medscape.com as part of the Gatekeepers of Care series on issues oncologists and people with cancer face navigating health insurance company requirements. Read more about the series here. Please email vstern@medscape.net to share experiences with prior authorization or other challenges receiving care.

The U.S. Food and Drug Administration on Dec. 8 approved two gene-editing treatments for patients aged 12 years or older with severe sickle cell disease.

These “milestone treatments” mark the first cell-based gene therapies for this debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States.

The two therapies are exagamglogene autotemcel, or exa-cel (Casgevy; Vertex Pharmaceuticals and Crispr Therapeutics), and lovotibeglogene autotemcel, or lovo-cel (Lyfgenia; bluebird bio). 

“The approval of the first gene therapies for [sickle cell disease] represents a tremendous step forward for the [sickle cell] community, which has been historically overlooked and underfunded,” said Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, in a statement from the American Society of Hematology, following the approval.

“We are excited to advance the field, especially for individuals whose lives have been severely disrupted by the disease, by approving two cell-based gene therapies today,” Nicole Verdun, MD, of the FDA’s Center for Biologics Evaluation and Research, added in an agency press release.

Sickle cell disease involves a mutation in hemoglobin, a protein in red blood cells that provides oxygen to tissues. The mutation leads red blood cells to develop a crescent or sickle shape, which can restrict blood flow and cause severe pain and organ damage, known as vaso-occlusive events or crises. 

Treatment options prior to these approvals primarily included red blood transfusions and hydroxyurea alongside pain management. The only potential curative option has been allogeneic hematopoietic stem cell transplantation, but that comes with significant risks and most patients don’t have an appropriate donor.

Exa-cel

Exa-cel uses CRISPR gene-editing technology. Before the infusion, patients undergo myeloablative conditioning, which removes cells from the bone marrow. These cells are genetically modified to produce fetal hemoglobin. Patients then receive an infusion of the edited cells, which can help restore normal hemoglobin production. 

The FDA approval was based on data from the pivotal CLIMB SCD-121 trial. In an October advisory committee meeting, the FDA highlighted trial data demonstrating that 29 of 31 patients reached the trial’s primary endpoint: freedom from severe vaso-occlusive crises over a 12-month period. In addition, 28 of these patients remained free of vaso-occlusive crises for almost 2 years.

The committee noted that one of the 31 patients died about 9 months after receiving an exa-cel infusion. 

The cell-based gene therapy also increased both fetal and total hemoglobin, with total hemoglobin levels increasing to > 11 g/dL by month 3 and remaining at that level afterward. No patients experienced graft failure or rejection.

The most common side effects included low platelets and white blood cell counts, mouth sores, nausea, musculoskeletal pain, vomiting, and febrile neutropenia. 

Exa-cel could “provide a one-time functional cure” for patients with severe sickle cell disease, according to Franco Locatelli, MD, of Sapienza University of Rome, who presented initial findings last year.

While the current approval is for patients with infusion-dependent sickle cell disease, exa-cel is also being evaluated in patients with another blood disorder, beta-thalassemia.

Lovo-cel

Lovo-cel, a cell-based gene therapy, uses a different technology — a lentiviral vector, or gene delivery vehicle — that can also genetically modify a patient’s blood stem cells. 

Like exa-cel, lovo-cel is a one-time, single-dose infusion that contains the patient’s modified cells. Before the infusion, patients undergo myeloablative conditioning. The patient’s stem cells are then genetically modified to allow them to produce the most common form of hemoglobin, HbA 

This approval was based on data from a single-arm, 24-month study in patients aged 12-50 years who had sickle cell disease and a history of vaso-occlusive events. 

Overall, 88% of patients (28 of 32) achieved complete resolution of vaso-occlusive events 6-18 months after the infusion. 

The most common side effects included stomatitis; febrile neutropenia; and low platelet, white blood cell, and red blood cell counts.

The FDA noted that hematologic cancer has occurred in patients treated with lovo-cel, and the label includes a black-box warning about the risk. 

Dr. Brodsky noted, however, that “while these new gene therapies are potentially life-changing for individuals living with [sickle cell disease], they must be accessible to be effective.”

Access is a potential concern. Exa-cel and lovo-cel could cost about $2 million.
 

A version of this article appeared on Medscape.com.

The U.S. Food and Drug Administration on Dec. 8 approved two gene-editing treatments for patients aged 12 years or older with severe sickle cell disease.

These “milestone treatments” mark the first cell-based gene therapies for this debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States.

The two therapies are exagamglogene autotemcel, or exa-cel (Casgevy; Vertex Pharmaceuticals and Crispr Therapeutics), and lovotibeglogene autotemcel, or lovo-cel (Lyfgenia; bluebird bio). 

“The approval of the first gene therapies for [sickle cell disease] represents a tremendous step forward for the [sickle cell] community, which has been historically overlooked and underfunded,” said Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, in a statement from the American Society of Hematology, following the approval.

“We are excited to advance the field, especially for individuals whose lives have been severely disrupted by the disease, by approving two cell-based gene therapies today,” Nicole Verdun, MD, of the FDA’s Center for Biologics Evaluation and Research, added in an agency press release.

Sickle cell disease involves a mutation in hemoglobin, a protein in red blood cells that provides oxygen to tissues. The mutation leads red blood cells to develop a crescent or sickle shape, which can restrict blood flow and cause severe pain and organ damage, known as vaso-occlusive events or crises. 

Treatment options prior to these approvals primarily included red blood transfusions and hydroxyurea alongside pain management. The only potential curative option has been allogeneic hematopoietic stem cell transplantation, but that comes with significant risks and most patients don’t have an appropriate donor.

Exa-cel

Exa-cel uses CRISPR gene-editing technology. Before the infusion, patients undergo myeloablative conditioning, which removes cells from the bone marrow. These cells are genetically modified to produce fetal hemoglobin. Patients then receive an infusion of the edited cells, which can help restore normal hemoglobin production. 

The FDA approval was based on data from the pivotal CLIMB SCD-121 trial. In an October advisory committee meeting, the FDA highlighted trial data demonstrating that 29 of 31 patients reached the trial’s primary endpoint: freedom from severe vaso-occlusive crises over a 12-month period. In addition, 28 of these patients remained free of vaso-occlusive crises for almost 2 years.

The committee noted that one of the 31 patients died about 9 months after receiving an exa-cel infusion. 

The cell-based gene therapy also increased both fetal and total hemoglobin, with total hemoglobin levels increasing to > 11 g/dL by month 3 and remaining at that level afterward. No patients experienced graft failure or rejection.

The most common side effects included low platelets and white blood cell counts, mouth sores, nausea, musculoskeletal pain, vomiting, and febrile neutropenia. 

Exa-cel could “provide a one-time functional cure” for patients with severe sickle cell disease, according to Franco Locatelli, MD, of Sapienza University of Rome, who presented initial findings last year.

While the current approval is for patients with infusion-dependent sickle cell disease, exa-cel is also being evaluated in patients with another blood disorder, beta-thalassemia.

Lovo-cel

Lovo-cel, a cell-based gene therapy, uses a different technology — a lentiviral vector, or gene delivery vehicle — that can also genetically modify a patient’s blood stem cells. 

Like exa-cel, lovo-cel is a one-time, single-dose infusion that contains the patient’s modified cells. Before the infusion, patients undergo myeloablative conditioning. The patient’s stem cells are then genetically modified to allow them to produce the most common form of hemoglobin, HbA 

This approval was based on data from a single-arm, 24-month study in patients aged 12-50 years who had sickle cell disease and a history of vaso-occlusive events. 

Overall, 88% of patients (28 of 32) achieved complete resolution of vaso-occlusive events 6-18 months after the infusion. 

The most common side effects included stomatitis; febrile neutropenia; and low platelet, white blood cell, and red blood cell counts.

The FDA noted that hematologic cancer has occurred in patients treated with lovo-cel, and the label includes a black-box warning about the risk. 

Dr. Brodsky noted, however, that “while these new gene therapies are potentially life-changing for individuals living with [sickle cell disease], they must be accessible to be effective.”

Access is a potential concern. Exa-cel and lovo-cel could cost about $2 million.
 

A version of this article appeared on Medscape.com.

The U.S. Food and Drug Administration on Dec. 8 approved two gene-editing treatments for patients aged 12 years or older with severe sickle cell disease.

These “milestone treatments” mark the first cell-based gene therapies for this debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States.

The two therapies are exagamglogene autotemcel, or exa-cel (Casgevy; Vertex Pharmaceuticals and Crispr Therapeutics), and lovotibeglogene autotemcel, or lovo-cel (Lyfgenia; bluebird bio). 

“The approval of the first gene therapies for [sickle cell disease] represents a tremendous step forward for the [sickle cell] community, which has been historically overlooked and underfunded,” said Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, in a statement from the American Society of Hematology, following the approval.

“We are excited to advance the field, especially for individuals whose lives have been severely disrupted by the disease, by approving two cell-based gene therapies today,” Nicole Verdun, MD, of the FDA’s Center for Biologics Evaluation and Research, added in an agency press release.

Sickle cell disease involves a mutation in hemoglobin, a protein in red blood cells that provides oxygen to tissues. The mutation leads red blood cells to develop a crescent or sickle shape, which can restrict blood flow and cause severe pain and organ damage, known as vaso-occlusive events or crises. 

Treatment options prior to these approvals primarily included red blood transfusions and hydroxyurea alongside pain management. The only potential curative option has been allogeneic hematopoietic stem cell transplantation, but that comes with significant risks and most patients don’t have an appropriate donor.

Exa-cel

Exa-cel uses CRISPR gene-editing technology. Before the infusion, patients undergo myeloablative conditioning, which removes cells from the bone marrow. These cells are genetically modified to produce fetal hemoglobin. Patients then receive an infusion of the edited cells, which can help restore normal hemoglobin production. 

The FDA approval was based on data from the pivotal CLIMB SCD-121 trial. In an October advisory committee meeting, the FDA highlighted trial data demonstrating that 29 of 31 patients reached the trial’s primary endpoint: freedom from severe vaso-occlusive crises over a 12-month period. In addition, 28 of these patients remained free of vaso-occlusive crises for almost 2 years.

The committee noted that one of the 31 patients died about 9 months after receiving an exa-cel infusion. 

The cell-based gene therapy also increased both fetal and total hemoglobin, with total hemoglobin levels increasing to > 11 g/dL by month 3 and remaining at that level afterward. No patients experienced graft failure or rejection.

The most common side effects included low platelets and white blood cell counts, mouth sores, nausea, musculoskeletal pain, vomiting, and febrile neutropenia. 

Exa-cel could “provide a one-time functional cure” for patients with severe sickle cell disease, according to Franco Locatelli, MD, of Sapienza University of Rome, who presented initial findings last year.

While the current approval is for patients with infusion-dependent sickle cell disease, exa-cel is also being evaluated in patients with another blood disorder, beta-thalassemia.

Lovo-cel

Lovo-cel, a cell-based gene therapy, uses a different technology — a lentiviral vector, or gene delivery vehicle — that can also genetically modify a patient’s blood stem cells. 

Like exa-cel, lovo-cel is a one-time, single-dose infusion that contains the patient’s modified cells. Before the infusion, patients undergo myeloablative conditioning. The patient’s stem cells are then genetically modified to allow them to produce the most common form of hemoglobin, HbA 

This approval was based on data from a single-arm, 24-month study in patients aged 12-50 years who had sickle cell disease and a history of vaso-occlusive events. 

Overall, 88% of patients (28 of 32) achieved complete resolution of vaso-occlusive events 6-18 months after the infusion. 

The most common side effects included stomatitis; febrile neutropenia; and low platelet, white blood cell, and red blood cell counts.

The FDA noted that hematologic cancer has occurred in patients treated with lovo-cel, and the label includes a black-box warning about the risk. 

Dr. Brodsky noted, however, that “while these new gene therapies are potentially life-changing for individuals living with [sickle cell disease], they must be accessible to be effective.”

Access is a potential concern. Exa-cel and lovo-cel could cost about $2 million.
 

A version of this article appeared on Medscape.com.

It was Friday, and oncologist Coral Olazagasti, MD, faced a ticking clock.

Her patient had taken his last prescription antinausea pill. Without a refill of ondansetron, he faced a long, painful weekend.

The patient – a man with HPV-related oropharyngeal cancer – was experiencing severe side effects from standard chemoradiation with weekly cisplatin. Intense nausea and grade 3 mucositis, in particular, left him struggling to swallow or take in any food or fluids.

He was on 8 mg of ondansetron (Zofran) every 8 hours, as needed, to keep the nausea at bay. The pills along with a feeding tube helped, but his symptoms were so intense, neither was quite enough.

“He still needed to be hospitalized twice for dehydration,” said Dr. Olazagasti, who specializes in head and neck medical cancer at Sylvester Comprehensive Cancer Center in Miami.

But when it came time to renew his ondansetron prescription, his insurance company denied it.

The reasoning: “The company had only approved 30 tablets a month and, for them, it was unjustifiable to approve anything above that amount,” Dr. Olazagasti explained.

After Dr. Olazagasti called the insurance company to resolve the issue, a company representative told her to fill out a prior authorization form.

But it was already after 7:30 p.m. ET on Friday.

At that point, finding the prior authorization documents, filling them out, and submitting them would take more time – and the paperwork couldn’t be filed until Monday.

“My patient was at home with zero tablets left and horrible symptoms. He couldn’t keep anything down,” Dr. Olazagasti said.

On Monday, the oncology team sent the prior authorization request, and her patient received his medication a few days later.

“My patient had to wait about 5 days to get the nausea meds he needed,” she said. In the meantime, he was in pain. “Having a refill of this simple supportive care medication rejected was infuriating.”

When Dr. Olazagasti vented her frustrations on Twitter, several people chimed in, suggesting purchasing the drug at a discount through GoodRx or Cost Plus instead of going through the insurance company.

At Cost Plus, for instance, 30 8-mg pills would cost $6.30, but ordering from the online pharmacy would mean waiting several days for delivery.

Discounts through GoodRx may provide a potentially faster solution in a pinch, but the pharmacy matters. In Miami, 30 8-mg pills would cost $19.99 at Costco with a GoodRx coupon, but $233.56 at CVS and $253.60 at Walgreens.

Although potentially useful, these options may not be the obvious choice for oncologists and patients, especially when a drug has already been approved and covered by the insurer. In this case, the denial was also a surprise, which left Dr. Olazagasti and her patient scrambling right before the weekend.

In addition, companies providing discounted generic drugs may only have a limited number of oncology-related medications. Cost Plus, for instance, now sells more than 1,000 generic prescription drugs at a fraction of what insurance companies charge, but only about 7 are cancer drugs.

On a broader level, Dr. Olazagasti noted, “insurance companies have a responsibility to cover these drugs. If we all get so fed up that we start relying on alternate routes to get patients their treatments, then insurance companies are let off the hook.”

However, using an alternative option like GoodRx or CostPlus could mean bypassing insurance company obstacles in certain cases.

“The hurdles someone may have to go through to get a generic drug approved are very frustrating,” said Stacie B. Dusetzina, PhD, professor of health policy and a professor of cancer research at Vanderbilt University in Nashville, Tenn.

In a weekend emergency situation, if the drug is discounted through GoodRx, “it can be a good backup strategy to send the prescription to the pharmacy” and more generally “worth it for patients to check if they can get a better deal on generic drugs through these companies.”

A version of this article first appeared on Medscape.com.

It was Friday, and oncologist Coral Olazagasti, MD, faced a ticking clock.

Her patient had taken his last prescription antinausea pill. Without a refill of ondansetron, he faced a long, painful weekend.

The patient – a man with HPV-related oropharyngeal cancer – was experiencing severe side effects from standard chemoradiation with weekly cisplatin. Intense nausea and grade 3 mucositis, in particular, left him struggling to swallow or take in any food or fluids.

He was on 8 mg of ondansetron (Zofran) every 8 hours, as needed, to keep the nausea at bay. The pills along with a feeding tube helped, but his symptoms were so intense, neither was quite enough.

“He still needed to be hospitalized twice for dehydration,” said Dr. Olazagasti, who specializes in head and neck medical cancer at Sylvester Comprehensive Cancer Center in Miami.

But when it came time to renew his ondansetron prescription, his insurance company denied it.

The reasoning: “The company had only approved 30 tablets a month and, for them, it was unjustifiable to approve anything above that amount,” Dr. Olazagasti explained.

After Dr. Olazagasti called the insurance company to resolve the issue, a company representative told her to fill out a prior authorization form.

But it was already after 7:30 p.m. ET on Friday.

At that point, finding the prior authorization documents, filling them out, and submitting them would take more time – and the paperwork couldn’t be filed until Monday.

“My patient was at home with zero tablets left and horrible symptoms. He couldn’t keep anything down,” Dr. Olazagasti said.

On Monday, the oncology team sent the prior authorization request, and her patient received his medication a few days later.

“My patient had to wait about 5 days to get the nausea meds he needed,” she said. In the meantime, he was in pain. “Having a refill of this simple supportive care medication rejected was infuriating.”

When Dr. Olazagasti vented her frustrations on Twitter, several people chimed in, suggesting purchasing the drug at a discount through GoodRx or Cost Plus instead of going through the insurance company.

At Cost Plus, for instance, 30 8-mg pills would cost $6.30, but ordering from the online pharmacy would mean waiting several days for delivery.

Discounts through GoodRx may provide a potentially faster solution in a pinch, but the pharmacy matters. In Miami, 30 8-mg pills would cost $19.99 at Costco with a GoodRx coupon, but $233.56 at CVS and $253.60 at Walgreens.

Although potentially useful, these options may not be the obvious choice for oncologists and patients, especially when a drug has already been approved and covered by the insurer. In this case, the denial was also a surprise, which left Dr. Olazagasti and her patient scrambling right before the weekend.

In addition, companies providing discounted generic drugs may only have a limited number of oncology-related medications. Cost Plus, for instance, now sells more than 1,000 generic prescription drugs at a fraction of what insurance companies charge, but only about 7 are cancer drugs.

On a broader level, Dr. Olazagasti noted, “insurance companies have a responsibility to cover these drugs. If we all get so fed up that we start relying on alternate routes to get patients their treatments, then insurance companies are let off the hook.”

However, using an alternative option like GoodRx or CostPlus could mean bypassing insurance company obstacles in certain cases.

“The hurdles someone may have to go through to get a generic drug approved are very frustrating,” said Stacie B. Dusetzina, PhD, professor of health policy and a professor of cancer research at Vanderbilt University in Nashville, Tenn.

In a weekend emergency situation, if the drug is discounted through GoodRx, “it can be a good backup strategy to send the prescription to the pharmacy” and more generally “worth it for patients to check if they can get a better deal on generic drugs through these companies.”

A version of this article first appeared on Medscape.com.

It was Friday, and oncologist Coral Olazagasti, MD, faced a ticking clock.

Her patient had taken his last prescription antinausea pill. Without a refill of ondansetron, he faced a long, painful weekend.

The patient – a man with HPV-related oropharyngeal cancer – was experiencing severe side effects from standard chemoradiation with weekly cisplatin. Intense nausea and grade 3 mucositis, in particular, left him struggling to swallow or take in any food or fluids.

He was on 8 mg of ondansetron (Zofran) every 8 hours, as needed, to keep the nausea at bay. The pills along with a feeding tube helped, but his symptoms were so intense, neither was quite enough.

“He still needed to be hospitalized twice for dehydration,” said Dr. Olazagasti, who specializes in head and neck medical cancer at Sylvester Comprehensive Cancer Center in Miami.

But when it came time to renew his ondansetron prescription, his insurance company denied it.

The reasoning: “The company had only approved 30 tablets a month and, for them, it was unjustifiable to approve anything above that amount,” Dr. Olazagasti explained.

After Dr. Olazagasti called the insurance company to resolve the issue, a company representative told her to fill out a prior authorization form.

But it was already after 7:30 p.m. ET on Friday.

At that point, finding the prior authorization documents, filling them out, and submitting them would take more time – and the paperwork couldn’t be filed until Monday.

“My patient was at home with zero tablets left and horrible symptoms. He couldn’t keep anything down,” Dr. Olazagasti said.

On Monday, the oncology team sent the prior authorization request, and her patient received his medication a few days later.

“My patient had to wait about 5 days to get the nausea meds he needed,” she said. In the meantime, he was in pain. “Having a refill of this simple supportive care medication rejected was infuriating.”

When Dr. Olazagasti vented her frustrations on Twitter, several people chimed in, suggesting purchasing the drug at a discount through GoodRx or Cost Plus instead of going through the insurance company.

At Cost Plus, for instance, 30 8-mg pills would cost $6.30, but ordering from the online pharmacy would mean waiting several days for delivery.

Discounts through GoodRx may provide a potentially faster solution in a pinch, but the pharmacy matters. In Miami, 30 8-mg pills would cost $19.99 at Costco with a GoodRx coupon, but $233.56 at CVS and $253.60 at Walgreens.

Although potentially useful, these options may not be the obvious choice for oncologists and patients, especially when a drug has already been approved and covered by the insurer. In this case, the denial was also a surprise, which left Dr. Olazagasti and her patient scrambling right before the weekend.

In addition, companies providing discounted generic drugs may only have a limited number of oncology-related medications. Cost Plus, for instance, now sells more than 1,000 generic prescription drugs at a fraction of what insurance companies charge, but only about 7 are cancer drugs.

On a broader level, Dr. Olazagasti noted, “insurance companies have a responsibility to cover these drugs. If we all get so fed up that we start relying on alternate routes to get patients their treatments, then insurance companies are let off the hook.”

However, using an alternative option like GoodRx or CostPlus could mean bypassing insurance company obstacles in certain cases.

“The hurdles someone may have to go through to get a generic drug approved are very frustrating,” said Stacie B. Dusetzina, PhD, professor of health policy and a professor of cancer research at Vanderbilt University in Nashville, Tenn.

In a weekend emergency situation, if the drug is discounted through GoodRx, “it can be a good backup strategy to send the prescription to the pharmacy” and more generally “worth it for patients to check if they can get a better deal on generic drugs through these companies.”

A version of this article first appeared on Medscape.com.

“Is this really the hill you want to die on?” asked Rebecca Shatsky, MD, a medical oncologist at the University of California, San Diego.

It was Nov. 18 and Dr. Shatsky was on the phone with a retired oncologist working for the health insurance company Premera Blue Cross.

Dr. Shatsky was appealing a prior authorization denial for pembrolizumab (Keytruda) to treat her patient with stage IIIc triple-negative breast cancer (TNBC). She hoped the peer-to-peer would reverse the denial. The Food and Drug Administration had approved the immunotherapy for people with high-risk TNBC both in the neoadjuvant setting alongside chemotherapy and, in her patient’s case, as a single-agent adjuvant treatment based on data from the KEYNOTE 522 trial.

In the peer-to-peer, Dr. Shatsky laid out the evidence, but she could tell the physician wasn’t going to budge.

When she pressed him further, asking why he was denying potentially lifesaving care for her patient, he said the data on whether patients really need adjuvant pembrolizumab were not clear yet.

“The man – who was not a breast oncologist – was essentially mansplaining breast oncology to me,” she said in an interview. “I don’t need a nonexpert giving me their misinterpretation of the data.”

Dr. Shatsky informed him that this decision would not stand. She would be escalating the claim.

“I’m not going to let you get in way of my patient’s survival,” Dr. Shatsky told the physician during the peer-to-peer. “We have one shot to cure this, and if we don’t do it now, patients’ average lifespan is 17 months.”

The conversation turned a few heads in her office.

“My whole office stopped and stared. But then they clapped after they realized why I was yelling,” she tweeted later that night.

She continued: “@premera picked the wrong oncologist to mess with today. I will not be letting this go. This denial. Will. Not. Stand. An insurance company should not get to tell me how to practice medicine when Phase III RCT data and @NCCN + @ASCO guideline support my decision!”

A spokesperson for Premera said in a statement that, “while we did see many of the details about the case were posted to Twitter, we cannot comment on the specifics you noted due to privacy policies.”

The spokesperson explained that Premera has “the same goal as our provider partners: ensure our members have access to quality health care,” noting that prior authorization helps health plans evaluate the medical necessity and safety of health care services given that “15%-30% of care is unnecessary.”

“We also understand that providers may not agree with our decisions, which is why we have a robust appeals process,” the spokesperson said, suggesting Dr. Shatsky could have appealed the decision a second time.

And “if the member or provider still disagrees with Premera’s coverage decision after the initial appeal, providers can request review by a medical expert outside Premera who works for an independent review organization,” and the company “will pay for” and “abide by” that decision, the spokesperson added.
 

The Twitter storm

After Dr. Shatsky tweeted about her experience with Premera, she received a flood of support from the Twitterverse. The thread garnered tens of thousands of likes and hundreds of comments offering support and advice.

Several people suggested asking Merck for help accessing the drug. But Dr. Shatsky said no, “I’m tired of laying down and letting [insurance companies] win. It IS worth fighting for.”

The next morning, Dr. Shatsky got a call. It was the vice president of medical management at Premera.

“We’ve talked again, and we’ll give you the drug,” Dr. Shatsky recalled the Premera vice president saying.

The next day, Monday morning, Dr. Shatsky’s patient received her first infusion of pembrolizumab.

Although relieved, Dr. Shatsky noted that it wasn’t until she posted her experience to Twitter that Premera seemed to take notice.

According to health policy expert Kelly Anderson, PhD, MPP, getting patients the cancer care they need should not require an oncologist venting on social media. Plus, “an oncologist without a strong social media following may not have gotten care approved and that’s not how medicine should work,” said Dr. Anderson, assistant professor in the department of clinical pharmacy, University of Colorado at Denver, Aurora.

Tatiana Prowell, MD, expressed similar concerns in a Nov. 20 tweet: “And sadly, the patients with cancer & an even busier, more exhausted doctor who doesn’t have a big [reach] on social media will be denied appropriate care. And that’s bank for insurers.”

But, Dr. Prowell noted sarcastically: “At least a patient with cancer had her care delayed & a dedicated OncTwitter colleague’s Physician Burnout was exacerbated.”

In this case, the prior authorization process took about a week – requiring an initial prior authorization request, an appeal after the request was denied, a peer-to-peer resulting in a second denial, and finally a tweet and a phone call from a top executive at the company.

In fact, these delays have become so common that Dr. Shatsky needs to anticipate and incorporate likely delays into her workflow.

“I learn which drugs will take a long time to get prior authorization for and then plan enough time so that my patient’s care is hopefully not delayed,” Dr. Shatsky said. “It should not be so hard to get appropriate and time-sensitive care for our patients.”

A version of this article first appeared on Medscape.com.

“Is this really the hill you want to die on?” asked Rebecca Shatsky, MD, a medical oncologist at the University of California, San Diego.

It was Nov. 18 and Dr. Shatsky was on the phone with a retired oncologist working for the health insurance company Premera Blue Cross.

Dr. Shatsky was appealing a prior authorization denial for pembrolizumab (Keytruda) to treat her patient with stage IIIc triple-negative breast cancer (TNBC). She hoped the peer-to-peer would reverse the denial. The Food and Drug Administration had approved the immunotherapy for people with high-risk TNBC both in the neoadjuvant setting alongside chemotherapy and, in her patient’s case, as a single-agent adjuvant treatment based on data from the KEYNOTE 522 trial.

In the peer-to-peer, Dr. Shatsky laid out the evidence, but she could tell the physician wasn’t going to budge.

When she pressed him further, asking why he was denying potentially lifesaving care for her patient, he said the data on whether patients really need adjuvant pembrolizumab were not clear yet.

“The man – who was not a breast oncologist – was essentially mansplaining breast oncology to me,” she said in an interview. “I don’t need a nonexpert giving me their misinterpretation of the data.”

Dr. Shatsky informed him that this decision would not stand. She would be escalating the claim.

“I’m not going to let you get in way of my patient’s survival,” Dr. Shatsky told the physician during the peer-to-peer. “We have one shot to cure this, and if we don’t do it now, patients’ average lifespan is 17 months.”

The conversation turned a few heads in her office.

“My whole office stopped and stared. But then they clapped after they realized why I was yelling,” she tweeted later that night.

She continued: “@premera picked the wrong oncologist to mess with today. I will not be letting this go. This denial. Will. Not. Stand. An insurance company should not get to tell me how to practice medicine when Phase III RCT data and @NCCN + @ASCO guideline support my decision!”

A spokesperson for Premera said in a statement that, “while we did see many of the details about the case were posted to Twitter, we cannot comment on the specifics you noted due to privacy policies.”

The spokesperson explained that Premera has “the same goal as our provider partners: ensure our members have access to quality health care,” noting that prior authorization helps health plans evaluate the medical necessity and safety of health care services given that “15%-30% of care is unnecessary.”

“We also understand that providers may not agree with our decisions, which is why we have a robust appeals process,” the spokesperson said, suggesting Dr. Shatsky could have appealed the decision a second time.

And “if the member or provider still disagrees with Premera’s coverage decision after the initial appeal, providers can request review by a medical expert outside Premera who works for an independent review organization,” and the company “will pay for” and “abide by” that decision, the spokesperson added.
 

The Twitter storm

After Dr. Shatsky tweeted about her experience with Premera, she received a flood of support from the Twitterverse. The thread garnered tens of thousands of likes and hundreds of comments offering support and advice.

Several people suggested asking Merck for help accessing the drug. But Dr. Shatsky said no, “I’m tired of laying down and letting [insurance companies] win. It IS worth fighting for.”

The next morning, Dr. Shatsky got a call. It was the vice president of medical management at Premera.

“We’ve talked again, and we’ll give you the drug,” Dr. Shatsky recalled the Premera vice president saying.

The next day, Monday morning, Dr. Shatsky’s patient received her first infusion of pembrolizumab.

Although relieved, Dr. Shatsky noted that it wasn’t until she posted her experience to Twitter that Premera seemed to take notice.

According to health policy expert Kelly Anderson, PhD, MPP, getting patients the cancer care they need should not require an oncologist venting on social media. Plus, “an oncologist without a strong social media following may not have gotten care approved and that’s not how medicine should work,” said Dr. Anderson, assistant professor in the department of clinical pharmacy, University of Colorado at Denver, Aurora.

Tatiana Prowell, MD, expressed similar concerns in a Nov. 20 tweet: “And sadly, the patients with cancer & an even busier, more exhausted doctor who doesn’t have a big [reach] on social media will be denied appropriate care. And that’s bank for insurers.”

But, Dr. Prowell noted sarcastically: “At least a patient with cancer had her care delayed & a dedicated OncTwitter colleague’s Physician Burnout was exacerbated.”

In this case, the prior authorization process took about a week – requiring an initial prior authorization request, an appeal after the request was denied, a peer-to-peer resulting in a second denial, and finally a tweet and a phone call from a top executive at the company.

In fact, these delays have become so common that Dr. Shatsky needs to anticipate and incorporate likely delays into her workflow.

“I learn which drugs will take a long time to get prior authorization for and then plan enough time so that my patient’s care is hopefully not delayed,” Dr. Shatsky said. “It should not be so hard to get appropriate and time-sensitive care for our patients.”

A version of this article first appeared on Medscape.com.

“Is this really the hill you want to die on?” asked Rebecca Shatsky, MD, a medical oncologist at the University of California, San Diego.

It was Nov. 18 and Dr. Shatsky was on the phone with a retired oncologist working for the health insurance company Premera Blue Cross.

Dr. Shatsky was appealing a prior authorization denial for pembrolizumab (Keytruda) to treat her patient with stage IIIc triple-negative breast cancer (TNBC). She hoped the peer-to-peer would reverse the denial. The Food and Drug Administration had approved the immunotherapy for people with high-risk TNBC both in the neoadjuvant setting alongside chemotherapy and, in her patient’s case, as a single-agent adjuvant treatment based on data from the KEYNOTE 522 trial.

In the peer-to-peer, Dr. Shatsky laid out the evidence, but she could tell the physician wasn’t going to budge.

When she pressed him further, asking why he was denying potentially lifesaving care for her patient, he said the data on whether patients really need adjuvant pembrolizumab were not clear yet.

“The man – who was not a breast oncologist – was essentially mansplaining breast oncology to me,” she said in an interview. “I don’t need a nonexpert giving me their misinterpretation of the data.”

Dr. Shatsky informed him that this decision would not stand. She would be escalating the claim.

“I’m not going to let you get in way of my patient’s survival,” Dr. Shatsky told the physician during the peer-to-peer. “We have one shot to cure this, and if we don’t do it now, patients’ average lifespan is 17 months.”

The conversation turned a few heads in her office.

“My whole office stopped and stared. But then they clapped after they realized why I was yelling,” she tweeted later that night.

She continued: “@premera picked the wrong oncologist to mess with today. I will not be letting this go. This denial. Will. Not. Stand. An insurance company should not get to tell me how to practice medicine when Phase III RCT data and @NCCN + @ASCO guideline support my decision!”

A spokesperson for Premera said in a statement that, “while we did see many of the details about the case were posted to Twitter, we cannot comment on the specifics you noted due to privacy policies.”

The spokesperson explained that Premera has “the same goal as our provider partners: ensure our members have access to quality health care,” noting that prior authorization helps health plans evaluate the medical necessity and safety of health care services given that “15%-30% of care is unnecessary.”

“We also understand that providers may not agree with our decisions, which is why we have a robust appeals process,” the spokesperson said, suggesting Dr. Shatsky could have appealed the decision a second time.

And “if the member or provider still disagrees with Premera’s coverage decision after the initial appeal, providers can request review by a medical expert outside Premera who works for an independent review organization,” and the company “will pay for” and “abide by” that decision, the spokesperson added.
 

The Twitter storm

After Dr. Shatsky tweeted about her experience with Premera, she received a flood of support from the Twitterverse. The thread garnered tens of thousands of likes and hundreds of comments offering support and advice.

Several people suggested asking Merck for help accessing the drug. But Dr. Shatsky said no, “I’m tired of laying down and letting [insurance companies] win. It IS worth fighting for.”

The next morning, Dr. Shatsky got a call. It was the vice president of medical management at Premera.

“We’ve talked again, and we’ll give you the drug,” Dr. Shatsky recalled the Premera vice president saying.

The next day, Monday morning, Dr. Shatsky’s patient received her first infusion of pembrolizumab.

Although relieved, Dr. Shatsky noted that it wasn’t until she posted her experience to Twitter that Premera seemed to take notice.

According to health policy expert Kelly Anderson, PhD, MPP, getting patients the cancer care they need should not require an oncologist venting on social media. Plus, “an oncologist without a strong social media following may not have gotten care approved and that’s not how medicine should work,” said Dr. Anderson, assistant professor in the department of clinical pharmacy, University of Colorado at Denver, Aurora.

Tatiana Prowell, MD, expressed similar concerns in a Nov. 20 tweet: “And sadly, the patients with cancer & an even busier, more exhausted doctor who doesn’t have a big [reach] on social media will be denied appropriate care. And that’s bank for insurers.”

But, Dr. Prowell noted sarcastically: “At least a patient with cancer had her care delayed & a dedicated OncTwitter colleague’s Physician Burnout was exacerbated.”

In this case, the prior authorization process took about a week – requiring an initial prior authorization request, an appeal after the request was denied, a peer-to-peer resulting in a second denial, and finally a tweet and a phone call from a top executive at the company.

In fact, these delays have become so common that Dr. Shatsky needs to anticipate and incorporate likely delays into her workflow.

“I learn which drugs will take a long time to get prior authorization for and then plan enough time so that my patient’s care is hopefully not delayed,” Dr. Shatsky said. “It should not be so hard to get appropriate and time-sensitive care for our patients.”

A version of this article first appeared on Medscape.com.