FDA/CDC

Selpercatinib (Retevmo) becomes the first targeted therapy to be approved by the US Food and Drug Administration (FDA) for use in patients with cancer who have certain tumors that have an alteration (mutation or fusion) in the RET gene.

The drug is indicated for use in RET-positive tumors found in the following:

• Non–small cell lung cancer (NSCLC) that has spread in adult patients
• Advanced medullary thyroid cancer (MTC) or MTC that has spread in adult and pediatric patients (older than 12 years) who require systemic therapy
• Thyroid cancer that requires systemic therapy and that has stopped responding to or is not appropriate for radioactive iodine therapy in adult and pediatric (older than 12 years) patients.

Before initiating treatment, a RET gene alteration must be determined via laboratory testing, the FDA emphasized. However, no FDA-approved test is currently available for detecting RET fusions/mutations.
 

Approval based on responses in open-label trial

This was an accelerated approval based on the overall response rate (ORR) and duration of response (DOR) seen in an open-label clinical trial (the phase 1/2 LIBRETTO-001 study), which involved patients with each of the three types of tumors.

All patients received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

For this trial, identification of a RET gene alteration was prospectively determined in plasma or tumor tissue by local laboratories using next-generation sequencing, polymerase chain reaction testing, or fluorescence in situ hybridization, according to Eli Lilly, the company marketing selpercatinib. Immunohistochemistry was not used in the clinical trial.

Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR was 64%.

Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had not received any previous treatment. The ORR for these patients was 84%.

For both groups, among patients who responded to treatment, the response lasted more than 6 months.

“In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases,” LIBRETTO-001 lead investigator Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York, N.Y., said in an Eli Lilly press release.

“The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy,” Dr. Drilon added.

About 1% to 2% of NSCLC tumors are thought to have a RET alteration.

The same trial also included patients with thyroid cancer.

Efficacy for MTC was evaluated in 55 adult and pediatric (older than 12 years) patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The ORR in these patients was 69%.

In addition, selpercatinib was evaluated in 88 patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for these patients was 73%.

The trial also enrolled 19 patients with RET-positive thyroid cancer whose condition was refractory to radioactive iodine (RAI) treatment and who had received another prior systemic treatment. The ORR was 79%. Eight patients had received only RAI. The ORR for these patients was 100%.

In all the cases of thyroid cancer and lung cancer, among the patients who responded to treatment, the response lasted longer than 6 months.

“RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers,” Lori J. Wirth, MD, of Massachusetts General Hospital Cancer Center in Boston, noted in the company release.

A fact sheet from Eli Lilly notes that RET mutations are found in about 60% of sporadic MTC cases and in over 90% of familial MTC cases, and that RET fusions are found in approximately 10% to 20% of papillary thyroid cancers.

“For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET,” Dr. Wirth commented. “Based on the published data for this new medicine, as well as my personal experience treating patients, this may be a good treatment option.”

In the LIBRETTO-001 trial, the rate of discontinuations because of adverse reactions (ARs) was 5%, the company reported. The most common ARs, including laboratory abnormalities (≥25%), were increased aspartate aminotransferase level, increased alanine aminotransferase level, increased glucose level, decreased leukocyte count, decreased albumin level, decreased calcium level, dry mouth, diarrhea, increased creatinine level, increased alkaline phosphatase level, hypertension, fatigue, edema, decreased platelet count, increased total cholesterol level, rash, decreased sodium levels, and constipation. The most frequent serious AR (≥2%) was pneumonia.

The FDA warned that selpercatinib can cause hepatotoxicity, elevation in blood pressure, QT prolongation, bleeding, and allergic reactions. It may also be toxic to a fetus or newborn baby so should not be taken by pregnant or breastfeeding women.

Selpercatinib is currently being assessed in two phase 3 confirmatory trials. LIBRETTO-431 will test the drug in previously untreated patients with RET-positive NSCLC. LIBRETTO-531 involves treatment-naive patients with RET-positive MTC.

The company that developed selpercaptinib, Loxo Oncology, was acquired by Eli Lilly last year in an $8 billion takeover. This drug was billed as the most promising asset in that deal, alongside oral BTK inhibitor LOXO-305, according to a report in Pharmaphorum.

Loxo developed Vitrakvi (larotrectinib), the first TRK inhibitor to reach the market, as well as the follow-up drug LOXO-195. Both were acquired by Bayer ahead of the Lilly takeover, that report notes.

This article first appeared on Medscape.com.

Selpercatinib (Retevmo) becomes the first targeted therapy to be approved by the US Food and Drug Administration (FDA) for use in patients with cancer who have certain tumors that have an alteration (mutation or fusion) in the RET gene.

The drug is indicated for use in RET-positive tumors found in the following:

• Non–small cell lung cancer (NSCLC) that has spread in adult patients
• Advanced medullary thyroid cancer (MTC) or MTC that has spread in adult and pediatric patients (older than 12 years) who require systemic therapy
• Thyroid cancer that requires systemic therapy and that has stopped responding to or is not appropriate for radioactive iodine therapy in adult and pediatric (older than 12 years) patients.

Before initiating treatment, a RET gene alteration must be determined via laboratory testing, the FDA emphasized. However, no FDA-approved test is currently available for detecting RET fusions/mutations.
 

Approval based on responses in open-label trial

This was an accelerated approval based on the overall response rate (ORR) and duration of response (DOR) seen in an open-label clinical trial (the phase 1/2 LIBRETTO-001 study), which involved patients with each of the three types of tumors.

All patients received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

For this trial, identification of a RET gene alteration was prospectively determined in plasma or tumor tissue by local laboratories using next-generation sequencing, polymerase chain reaction testing, or fluorescence in situ hybridization, according to Eli Lilly, the company marketing selpercatinib. Immunohistochemistry was not used in the clinical trial.

Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR was 64%.

Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had not received any previous treatment. The ORR for these patients was 84%.

For both groups, among patients who responded to treatment, the response lasted more than 6 months.

“In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases,” LIBRETTO-001 lead investigator Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York, N.Y., said in an Eli Lilly press release.

“The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy,” Dr. Drilon added.

About 1% to 2% of NSCLC tumors are thought to have a RET alteration.

The same trial also included patients with thyroid cancer.

Efficacy for MTC was evaluated in 55 adult and pediatric (older than 12 years) patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The ORR in these patients was 69%.

In addition, selpercatinib was evaluated in 88 patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for these patients was 73%.

The trial also enrolled 19 patients with RET-positive thyroid cancer whose condition was refractory to radioactive iodine (RAI) treatment and who had received another prior systemic treatment. The ORR was 79%. Eight patients had received only RAI. The ORR for these patients was 100%.

In all the cases of thyroid cancer and lung cancer, among the patients who responded to treatment, the response lasted longer than 6 months.

“RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers,” Lori J. Wirth, MD, of Massachusetts General Hospital Cancer Center in Boston, noted in the company release.

A fact sheet from Eli Lilly notes that RET mutations are found in about 60% of sporadic MTC cases and in over 90% of familial MTC cases, and that RET fusions are found in approximately 10% to 20% of papillary thyroid cancers.

“For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET,” Dr. Wirth commented. “Based on the published data for this new medicine, as well as my personal experience treating patients, this may be a good treatment option.”

In the LIBRETTO-001 trial, the rate of discontinuations because of adverse reactions (ARs) was 5%, the company reported. The most common ARs, including laboratory abnormalities (≥25%), were increased aspartate aminotransferase level, increased alanine aminotransferase level, increased glucose level, decreased leukocyte count, decreased albumin level, decreased calcium level, dry mouth, diarrhea, increased creatinine level, increased alkaline phosphatase level, hypertension, fatigue, edema, decreased platelet count, increased total cholesterol level, rash, decreased sodium levels, and constipation. The most frequent serious AR (≥2%) was pneumonia.

The FDA warned that selpercatinib can cause hepatotoxicity, elevation in blood pressure, QT prolongation, bleeding, and allergic reactions. It may also be toxic to a fetus or newborn baby so should not be taken by pregnant or breastfeeding women.

Selpercatinib is currently being assessed in two phase 3 confirmatory trials. LIBRETTO-431 will test the drug in previously untreated patients with RET-positive NSCLC. LIBRETTO-531 involves treatment-naive patients with RET-positive MTC.

The company that developed selpercaptinib, Loxo Oncology, was acquired by Eli Lilly last year in an $8 billion takeover. This drug was billed as the most promising asset in that deal, alongside oral BTK inhibitor LOXO-305, according to a report in Pharmaphorum.

Loxo developed Vitrakvi (larotrectinib), the first TRK inhibitor to reach the market, as well as the follow-up drug LOXO-195. Both were acquired by Bayer ahead of the Lilly takeover, that report notes.

This article first appeared on Medscape.com.

Selpercatinib (Retevmo) becomes the first targeted therapy to be approved by the US Food and Drug Administration (FDA) for use in patients with cancer who have certain tumors that have an alteration (mutation or fusion) in the RET gene.

The drug is indicated for use in RET-positive tumors found in the following:

• Non–small cell lung cancer (NSCLC) that has spread in adult patients
• Advanced medullary thyroid cancer (MTC) or MTC that has spread in adult and pediatric patients (older than 12 years) who require systemic therapy
• Thyroid cancer that requires systemic therapy and that has stopped responding to or is not appropriate for radioactive iodine therapy in adult and pediatric (older than 12 years) patients.

Before initiating treatment, a RET gene alteration must be determined via laboratory testing, the FDA emphasized. However, no FDA-approved test is currently available for detecting RET fusions/mutations.
 

Approval based on responses in open-label trial

This was an accelerated approval based on the overall response rate (ORR) and duration of response (DOR) seen in an open-label clinical trial (the phase 1/2 LIBRETTO-001 study), which involved patients with each of the three types of tumors.

All patients received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

For this trial, identification of a RET gene alteration was prospectively determined in plasma or tumor tissue by local laboratories using next-generation sequencing, polymerase chain reaction testing, or fluorescence in situ hybridization, according to Eli Lilly, the company marketing selpercatinib. Immunohistochemistry was not used in the clinical trial.

Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR was 64%.

Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had not received any previous treatment. The ORR for these patients was 84%.

For both groups, among patients who responded to treatment, the response lasted more than 6 months.

“In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases,” LIBRETTO-001 lead investigator Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York, N.Y., said in an Eli Lilly press release.

“The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy,” Dr. Drilon added.

About 1% to 2% of NSCLC tumors are thought to have a RET alteration.

The same trial also included patients with thyroid cancer.

Efficacy for MTC was evaluated in 55 adult and pediatric (older than 12 years) patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The ORR in these patients was 69%.

In addition, selpercatinib was evaluated in 88 patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for these patients was 73%.

The trial also enrolled 19 patients with RET-positive thyroid cancer whose condition was refractory to radioactive iodine (RAI) treatment and who had received another prior systemic treatment. The ORR was 79%. Eight patients had received only RAI. The ORR for these patients was 100%.

In all the cases of thyroid cancer and lung cancer, among the patients who responded to treatment, the response lasted longer than 6 months.

“RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers,” Lori J. Wirth, MD, of Massachusetts General Hospital Cancer Center in Boston, noted in the company release.

A fact sheet from Eli Lilly notes that RET mutations are found in about 60% of sporadic MTC cases and in over 90% of familial MTC cases, and that RET fusions are found in approximately 10% to 20% of papillary thyroid cancers.

“For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET,” Dr. Wirth commented. “Based on the published data for this new medicine, as well as my personal experience treating patients, this may be a good treatment option.”

In the LIBRETTO-001 trial, the rate of discontinuations because of adverse reactions (ARs) was 5%, the company reported. The most common ARs, including laboratory abnormalities (≥25%), were increased aspartate aminotransferase level, increased alanine aminotransferase level, increased glucose level, decreased leukocyte count, decreased albumin level, decreased calcium level, dry mouth, diarrhea, increased creatinine level, increased alkaline phosphatase level, hypertension, fatigue, edema, decreased platelet count, increased total cholesterol level, rash, decreased sodium levels, and constipation. The most frequent serious AR (≥2%) was pneumonia.

The FDA warned that selpercatinib can cause hepatotoxicity, elevation in blood pressure, QT prolongation, bleeding, and allergic reactions. It may also be toxic to a fetus or newborn baby so should not be taken by pregnant or breastfeeding women.

Selpercatinib is currently being assessed in two phase 3 confirmatory trials. LIBRETTO-431 will test the drug in previously untreated patients with RET-positive NSCLC. LIBRETTO-531 involves treatment-naive patients with RET-positive MTC.

The company that developed selpercaptinib, Loxo Oncology, was acquired by Eli Lilly last year in an $8 billion takeover. This drug was billed as the most promising asset in that deal, alongside oral BTK inhibitor LOXO-305, according to a report in Pharmaphorum.

Loxo developed Vitrakvi (larotrectinib), the first TRK inhibitor to reach the market, as well as the follow-up drug LOXO-195. Both were acquired by Bayer ahead of the Lilly takeover, that report notes.

This article first appeared on Medscape.com.

The Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

The Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

The Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved capmatinib (Tabrecta) to treat adults with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, as detected by an FDA-approved test.

The FDA also approved the FoundationOne CDx assay (F1CDx) as a companion diagnostic for capmatinib. F1CDx is a next-generation sequencing-based, in vitro diagnostic device that detects several mutations, including MET exon 14 skipping mutations.

Capmatinib is a selective, reversible inhibitor of MET tyrosine kinase and the first treatment FDA-approved for NSCLC with MET exon 14 skipping mutations.

Capmatinib was granted accelerated approval based on overall response rate and response duration in the GEOMETRY mono-1 trial, the FDA said. Results from this trial were recently presented at the AACR Virtual Annual Meeting I.

The phase 2 trial enrolled 97 patients with metastatic NSCLC and confirmed MET exon 14 skipping mutations, 69 of whom were previously treated and 28 of whom were treatment naive. The patients received capmatinib at 400 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 68% in the treatment-naive patients and 41% in the previously treated patients. The median duration of response was 12.6 months and 9.7 months, respectively, according to the FDA.

The most common adverse events (occurring in at least 20% of patients) were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.

The full prescribing information for capmatinib is available for download from the FDA website.

The FDA granted the approval of capmatinib to Novartis Pharmaceuticals Corporation and the approval of the F1CDx companion diagnostic to Foundation Medicine.

jensmith@mdedge.com

The Food and Drug Administration has approved capmatinib (Tabrecta) to treat adults with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, as detected by an FDA-approved test.

The FDA also approved the FoundationOne CDx assay (F1CDx) as a companion diagnostic for capmatinib. F1CDx is a next-generation sequencing-based, in vitro diagnostic device that detects several mutations, including MET exon 14 skipping mutations.

Capmatinib is a selective, reversible inhibitor of MET tyrosine kinase and the first treatment FDA-approved for NSCLC with MET exon 14 skipping mutations.

Capmatinib was granted accelerated approval based on overall response rate and response duration in the GEOMETRY mono-1 trial, the FDA said. Results from this trial were recently presented at the AACR Virtual Annual Meeting I.

The phase 2 trial enrolled 97 patients with metastatic NSCLC and confirmed MET exon 14 skipping mutations, 69 of whom were previously treated and 28 of whom were treatment naive. The patients received capmatinib at 400 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 68% in the treatment-naive patients and 41% in the previously treated patients. The median duration of response was 12.6 months and 9.7 months, respectively, according to the FDA.

The most common adverse events (occurring in at least 20% of patients) were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.

The full prescribing information for capmatinib is available for download from the FDA website.

The FDA granted the approval of capmatinib to Novartis Pharmaceuticals Corporation and the approval of the F1CDx companion diagnostic to Foundation Medicine.

jensmith@mdedge.com

The Food and Drug Administration has approved capmatinib (Tabrecta) to treat adults with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, as detected by an FDA-approved test.

The FDA also approved the FoundationOne CDx assay (F1CDx) as a companion diagnostic for capmatinib. F1CDx is a next-generation sequencing-based, in vitro diagnostic device that detects several mutations, including MET exon 14 skipping mutations.

Capmatinib is a selective, reversible inhibitor of MET tyrosine kinase and the first treatment FDA-approved for NSCLC with MET exon 14 skipping mutations.

Capmatinib was granted accelerated approval based on overall response rate and response duration in the GEOMETRY mono-1 trial, the FDA said. Results from this trial were recently presented at the AACR Virtual Annual Meeting I.

The phase 2 trial enrolled 97 patients with metastatic NSCLC and confirmed MET exon 14 skipping mutations, 69 of whom were previously treated and 28 of whom were treatment naive. The patients received capmatinib at 400 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 68% in the treatment-naive patients and 41% in the previously treated patients. The median duration of response was 12.6 months and 9.7 months, respectively, according to the FDA.

The most common adverse events (occurring in at least 20% of patients) were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.

The full prescribing information for capmatinib is available for download from the FDA website.

The FDA granted the approval of capmatinib to Novartis Pharmaceuticals Corporation and the approval of the F1CDx companion diagnostic to Foundation Medicine.

jensmith@mdedge.com

The U.S. Food and Drug Administration is tightening requirements for companies that develop COVID-19 antibody tests in an effort to combat fraud and better regulate the frenzy of tests coming to market.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The updated policy, announced May 4, requires commercial antibody test developers to apply for Emergency Use Authorization (EUA) from the FDA under a tight time frame and also provides specific performance threshold recommendations for test specificity and sensitivity. The revised requirements follow a March 16 policy that allowed developers to validate their own tests and bring them to market without an agency review. More than 100 coronavirus antibody tests have since entered the market, fueling a congressional investigation into the accuracy of tests.

When the March policy was issued, FDA Commissioner Stephen M. Hahn, MD, said it was critical for the FDA to provide regulatory flexibility for serology test developers, given the nature of the COVID-19 public health emergency and an understanding that the tests were not meant to be used as the sole basis for COVID-19 diagnosis.

“As FDA has authorized more antibody tests and validation data has become available, including through the capability at [the National Cancer Institute] the careful balancing of risks and benefits has shifted to the approach we have outlined today and our policy update,” Dr. Hahn said during a May 4 press conference.

The new approach requires all commercial manufacturers to submit EUA requests with their validation data within 10 business days from the date they notified the FDA of their validation testing or from the date of the May 4 policy, whichever is later. Additionally, the FDA has provided specific performance threshold recommendations for specificity and sensitivity for all serology test developers.

In a statement released May 4, FDA leaders acknowledged the widespread fraud that is occurring in connection to antibody tests entering the market.

“We unfortunately see unscrupulous actors marketing fraudulent test kits and using the pandemic as an opportunity to take advantage of Americans’ anxiety,” wrote Anand Shah, MD, FDA deputy commissioner for medical and scientific affairs in a joint statement with Jeff E. Shuren, MD, director for the FDA’s Center for Devices and Radiological Health. “Some test developers have falsely claimed their serological tests are FDA approved or authorized. Others have falsely claimed that their tests can diagnose COVID-19 or that they are for at-home testing, which would fall outside of the policies outlined in our March 16 guidance, as well as the updated guidance.”

At the same time, FDA officials said they are aware of a “concerning number” of commercial serology tests that are being inappropriately marketed, including for diagnostic use, or that are performing poorly based on an independent evaluation by the National Institutes of Health, according to the May 4 statement.

In addition to tightening its requirements for test developers, the FDA also is introducing a more streamlined process to support EUA submissions and review. Two voluntary EUA templates for antibody tests are now available – one for commercial manufacturers and one for Clinical Laboratory Improvement Amendments-certified high-complexity labs seeking FDA authorization. The templates will facilitate the preparation and submission of EUA requests and can be used by any interested developer, according to the FDA.

To date, 12 antibody tests have been authorized under an individual EUA, and more than 200 antibody tests are currently the subject of a pre-EUA or EUA review, according to the FDA.

Many unknowns remain about antibody tests and how they might help researchers and clinicians understand and/or potentially treat COVID-19. Antibody tests may be able to provide information on disease prevalence and frequency of asymptomatic infection, as well as identify potential donors of “convalescent plasma,” an approach in which blood plasma containing antibodies from a recovered individual serves as a therapy for an infected patient with severe disease, Dr. Shah wrote in the May 4 statement.

“There are a lot of unanswered questions about this particular issue,” Dr. Hahn said during the press conference. “We need the data because we need to understand this particular aspect of the disease and put it as part of the puzzle around COVID-19.”

agallegos@mdedge.com

The U.S. Food and Drug Administration is tightening requirements for companies that develop COVID-19 antibody tests in an effort to combat fraud and better regulate the frenzy of tests coming to market.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The updated policy, announced May 4, requires commercial antibody test developers to apply for Emergency Use Authorization (EUA) from the FDA under a tight time frame and also provides specific performance threshold recommendations for test specificity and sensitivity. The revised requirements follow a March 16 policy that allowed developers to validate their own tests and bring them to market without an agency review. More than 100 coronavirus antibody tests have since entered the market, fueling a congressional investigation into the accuracy of tests.

When the March policy was issued, FDA Commissioner Stephen M. Hahn, MD, said it was critical for the FDA to provide regulatory flexibility for serology test developers, given the nature of the COVID-19 public health emergency and an understanding that the tests were not meant to be used as the sole basis for COVID-19 diagnosis.

“As FDA has authorized more antibody tests and validation data has become available, including through the capability at [the National Cancer Institute] the careful balancing of risks and benefits has shifted to the approach we have outlined today and our policy update,” Dr. Hahn said during a May 4 press conference.

The new approach requires all commercial manufacturers to submit EUA requests with their validation data within 10 business days from the date they notified the FDA of their validation testing or from the date of the May 4 policy, whichever is later. Additionally, the FDA has provided specific performance threshold recommendations for specificity and sensitivity for all serology test developers.

In a statement released May 4, FDA leaders acknowledged the widespread fraud that is occurring in connection to antibody tests entering the market.

“We unfortunately see unscrupulous actors marketing fraudulent test kits and using the pandemic as an opportunity to take advantage of Americans’ anxiety,” wrote Anand Shah, MD, FDA deputy commissioner for medical and scientific affairs in a joint statement with Jeff E. Shuren, MD, director for the FDA’s Center for Devices and Radiological Health. “Some test developers have falsely claimed their serological tests are FDA approved or authorized. Others have falsely claimed that their tests can diagnose COVID-19 or that they are for at-home testing, which would fall outside of the policies outlined in our March 16 guidance, as well as the updated guidance.”

At the same time, FDA officials said they are aware of a “concerning number” of commercial serology tests that are being inappropriately marketed, including for diagnostic use, or that are performing poorly based on an independent evaluation by the National Institutes of Health, according to the May 4 statement.

In addition to tightening its requirements for test developers, the FDA also is introducing a more streamlined process to support EUA submissions and review. Two voluntary EUA templates for antibody tests are now available – one for commercial manufacturers and one for Clinical Laboratory Improvement Amendments-certified high-complexity labs seeking FDA authorization. The templates will facilitate the preparation and submission of EUA requests and can be used by any interested developer, according to the FDA.

To date, 12 antibody tests have been authorized under an individual EUA, and more than 200 antibody tests are currently the subject of a pre-EUA or EUA review, according to the FDA.

Many unknowns remain about antibody tests and how they might help researchers and clinicians understand and/or potentially treat COVID-19. Antibody tests may be able to provide information on disease prevalence and frequency of asymptomatic infection, as well as identify potential donors of “convalescent plasma,” an approach in which blood plasma containing antibodies from a recovered individual serves as a therapy for an infected patient with severe disease, Dr. Shah wrote in the May 4 statement.

“There are a lot of unanswered questions about this particular issue,” Dr. Hahn said during the press conference. “We need the data because we need to understand this particular aspect of the disease and put it as part of the puzzle around COVID-19.”

agallegos@mdedge.com

The U.S. Food and Drug Administration is tightening requirements for companies that develop COVID-19 antibody tests in an effort to combat fraud and better regulate the frenzy of tests coming to market.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The updated policy, announced May 4, requires commercial antibody test developers to apply for Emergency Use Authorization (EUA) from the FDA under a tight time frame and also provides specific performance threshold recommendations for test specificity and sensitivity. The revised requirements follow a March 16 policy that allowed developers to validate their own tests and bring them to market without an agency review. More than 100 coronavirus antibody tests have since entered the market, fueling a congressional investigation into the accuracy of tests.

When the March policy was issued, FDA Commissioner Stephen M. Hahn, MD, said it was critical for the FDA to provide regulatory flexibility for serology test developers, given the nature of the COVID-19 public health emergency and an understanding that the tests were not meant to be used as the sole basis for COVID-19 diagnosis.

“As FDA has authorized more antibody tests and validation data has become available, including through the capability at [the National Cancer Institute] the careful balancing of risks and benefits has shifted to the approach we have outlined today and our policy update,” Dr. Hahn said during a May 4 press conference.

The new approach requires all commercial manufacturers to submit EUA requests with their validation data within 10 business days from the date they notified the FDA of their validation testing or from the date of the May 4 policy, whichever is later. Additionally, the FDA has provided specific performance threshold recommendations for specificity and sensitivity for all serology test developers.

In a statement released May 4, FDA leaders acknowledged the widespread fraud that is occurring in connection to antibody tests entering the market.

“We unfortunately see unscrupulous actors marketing fraudulent test kits and using the pandemic as an opportunity to take advantage of Americans’ anxiety,” wrote Anand Shah, MD, FDA deputy commissioner for medical and scientific affairs in a joint statement with Jeff E. Shuren, MD, director for the FDA’s Center for Devices and Radiological Health. “Some test developers have falsely claimed their serological tests are FDA approved or authorized. Others have falsely claimed that their tests can diagnose COVID-19 or that they are for at-home testing, which would fall outside of the policies outlined in our March 16 guidance, as well as the updated guidance.”

At the same time, FDA officials said they are aware of a “concerning number” of commercial serology tests that are being inappropriately marketed, including for diagnostic use, or that are performing poorly based on an independent evaluation by the National Institutes of Health, according to the May 4 statement.

In addition to tightening its requirements for test developers, the FDA also is introducing a more streamlined process to support EUA submissions and review. Two voluntary EUA templates for antibody tests are now available – one for commercial manufacturers and one for Clinical Laboratory Improvement Amendments-certified high-complexity labs seeking FDA authorization. The templates will facilitate the preparation and submission of EUA requests and can be used by any interested developer, according to the FDA.

To date, 12 antibody tests have been authorized under an individual EUA, and more than 200 antibody tests are currently the subject of a pre-EUA or EUA review, according to the FDA.

Many unknowns remain about antibody tests and how they might help researchers and clinicians understand and/or potentially treat COVID-19. Antibody tests may be able to provide information on disease prevalence and frequency of asymptomatic infection, as well as identify potential donors of “convalescent plasma,” an approach in which blood plasma containing antibodies from a recovered individual serves as a therapy for an infected patient with severe disease, Dr. Shah wrote in the May 4 statement.

“There are a lot of unanswered questions about this particular issue,” Dr. Hahn said during the press conference. “We need the data because we need to understand this particular aspect of the disease and put it as part of the puzzle around COVID-19.”

agallegos@mdedge.com

The US Food and Drug Administration (FDA) issued an emergency use authorization on May 1 for remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.

The investigational antiviral drug, manufactured by Gilead Sciences Inc., was shown in a preliminary analysis of a National Institutes of Health (NIH) clinical trial to shorten recovery time in some patients, according to information presented during a White House press conference earlier this week. However, the results of the trial have not been published and little is known about how safe and effective it is in treating people in the hospital with COVID-19.

The emergency use authorization (EUA) designation means remdesivir can be distributed in the United States and administered intravenously by healthcare providers, as appropriate to treat severe disease. Those with severe disease, the FDA said in a press release, are patients with low blood oxygen levels or those who need oxygen therapy or more intensive support such as a mechanical ventilator.

“There’s tremendous interest among all parties to identify and arm ourselves with medicines to combat COVID-19, and through our Coronavirus Treatment Acceleration Program, the FDA is working around-the-clock and using every tool at our disposal to speed these efforts,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.

The FDA writes, “Based on evaluation of the emergency use authorization criteria and the scientific evidence available, it was determined that it is reasonable to believe that remdesivir may be effective in treating COVID-19, and that, given there are no adequate, approved, or available alternative treatments, the known and potential benefits to treat this serious or life-threatening virus currently outweigh the known and potential risks of the drug’s use.”

The drug must be administered intravenously and the optimal dosing and duration are not yet known, the company said in a press release issued May 1.

In addition, Gilead advises that infusion-related reactions and liver transaminase elevations have been seen in patients treated with the drug.

“If signs and symptoms of a clinically significant infusion reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment. Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. Monitor renal and hepatic function prior to initiating and daily during therapy with remdesivir; additionally monitor serum chemistries and hematology daily during therapy,” the company said.

Before granting the emergency use authorization, the FDA had allowed for study of the drug in clinical trials, as well as expanded access use for individual patients and through a multipatient expanded access program coordinated by Gilead.

“The EUA will be effective until the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biologics for prevention and treatment of COVID-19 is terminated and may be revised or revoked if it is determined the EUA no longer meets the statutory criteria for issuance,” the FDA said.


This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) issued an emergency use authorization on May 1 for remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.

The investigational antiviral drug, manufactured by Gilead Sciences Inc., was shown in a preliminary analysis of a National Institutes of Health (NIH) clinical trial to shorten recovery time in some patients, according to information presented during a White House press conference earlier this week. However, the results of the trial have not been published and little is known about how safe and effective it is in treating people in the hospital with COVID-19.

The emergency use authorization (EUA) designation means remdesivir can be distributed in the United States and administered intravenously by healthcare providers, as appropriate to treat severe disease. Those with severe disease, the FDA said in a press release, are patients with low blood oxygen levels or those who need oxygen therapy or more intensive support such as a mechanical ventilator.

“There’s tremendous interest among all parties to identify and arm ourselves with medicines to combat COVID-19, and through our Coronavirus Treatment Acceleration Program, the FDA is working around-the-clock and using every tool at our disposal to speed these efforts,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.

The FDA writes, “Based on evaluation of the emergency use authorization criteria and the scientific evidence available, it was determined that it is reasonable to believe that remdesivir may be effective in treating COVID-19, and that, given there are no adequate, approved, or available alternative treatments, the known and potential benefits to treat this serious or life-threatening virus currently outweigh the known and potential risks of the drug’s use.”

The drug must be administered intravenously and the optimal dosing and duration are not yet known, the company said in a press release issued May 1.

In addition, Gilead advises that infusion-related reactions and liver transaminase elevations have been seen in patients treated with the drug.

“If signs and symptoms of a clinically significant infusion reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment. Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. Monitor renal and hepatic function prior to initiating and daily during therapy with remdesivir; additionally monitor serum chemistries and hematology daily during therapy,” the company said.

Before granting the emergency use authorization, the FDA had allowed for study of the drug in clinical trials, as well as expanded access use for individual patients and through a multipatient expanded access program coordinated by Gilead.

“The EUA will be effective until the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biologics for prevention and treatment of COVID-19 is terminated and may be revised or revoked if it is determined the EUA no longer meets the statutory criteria for issuance,” the FDA said.


This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) issued an emergency use authorization on May 1 for remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.

The investigational antiviral drug, manufactured by Gilead Sciences Inc., was shown in a preliminary analysis of a National Institutes of Health (NIH) clinical trial to shorten recovery time in some patients, according to information presented during a White House press conference earlier this week. However, the results of the trial have not been published and little is known about how safe and effective it is in treating people in the hospital with COVID-19.

The emergency use authorization (EUA) designation means remdesivir can be distributed in the United States and administered intravenously by healthcare providers, as appropriate to treat severe disease. Those with severe disease, the FDA said in a press release, are patients with low blood oxygen levels or those who need oxygen therapy or more intensive support such as a mechanical ventilator.

“There’s tremendous interest among all parties to identify and arm ourselves with medicines to combat COVID-19, and through our Coronavirus Treatment Acceleration Program, the FDA is working around-the-clock and using every tool at our disposal to speed these efforts,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.

The FDA writes, “Based on evaluation of the emergency use authorization criteria and the scientific evidence available, it was determined that it is reasonable to believe that remdesivir may be effective in treating COVID-19, and that, given there are no adequate, approved, or available alternative treatments, the known and potential benefits to treat this serious or life-threatening virus currently outweigh the known and potential risks of the drug’s use.”

The drug must be administered intravenously and the optimal dosing and duration are not yet known, the company said in a press release issued May 1.

In addition, Gilead advises that infusion-related reactions and liver transaminase elevations have been seen in patients treated with the drug.

“If signs and symptoms of a clinically significant infusion reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment. Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. Monitor renal and hepatic function prior to initiating and daily during therapy with remdesivir; additionally monitor serum chemistries and hematology daily during therapy,” the company said.

Before granting the emergency use authorization, the FDA had allowed for study of the drug in clinical trials, as well as expanded access use for individual patients and through a multipatient expanded access program coordinated by Gilead.

“The EUA will be effective until the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biologics for prevention and treatment of COVID-19 is terminated and may be revised or revoked if it is determined the EUA no longer meets the statutory criteria for issuance,” the FDA said.


This article first appeared on Medscape.com.

The sodium-glucose transporter 2 (SGLT-2) inhibitor ertugliflozin broke ranks with the other drugs in its class and failed to produce statistically significant drops in the both the combined incidence of cardiovascular (CV) death or heart failure hospitalization, and the rate of adverse renal outcomes, in the mandated CV outcomes trial run for ertugliflozin with more than 8,200 patients with type 2 diabetes and established CV disease.

Merck, one of the companies that markets the drug, announced the topline results in a quarterly financial report released on April 28, 2020.

According to the report, the results from the ertugliflozin cardiovascular outcomes trial “achieved its primary endpoint of noninferiority for major adverse CV events (MACE), compared to placebo in patients with type 2 diabetes mellitus and established atherosclerotic CV disease,” but “the key secondary endpoints of superiority” of ertugliflozin, compared with placebo, “for time to the composite of CV death or hospitalization for heart failure, CV death alone, and the composite of renal death, dialysis/transplant or doubling of serum creatinine from baseline were not met.”

However, the report added that, “while not a prespecified hypothesis for statistical testing, a reduction in hospitalization for heart failure was observed” with ertugliflozin treatment, and the report further said that the drug’s safety profile in the trial “was consistent with that reported in previous studies.” The statement closed by saying that detailed results from the trial are scheduled to be presented on June 16, 2020, at the virtual American Diabetes Association’s 80th Scientific Sessions.

These results came from the VERTIS CV (Evaluation of Ertugliflozin EffIcacy and Safety Cardiovascular Outcomes) trial, which researchers said in 2018 had administered at least one investigational dose to 8,238 randomized patients at centers in any of 34 countries during two enrollment periods in 2013-2015 and 2016-2017 (Am Heart J. 2018 Dec;206:11-23). The tested agent, ertugliflozin (Steglatro) received Food and Drug Administration marketing approval late in 2017 for the indication of improving glycemic control in patients with type 2 diabetes.

The FDA mandated cardiovascular outcomes trials for new glycemic control drugs in guidance the agency issued in 2008 (the FDA released in March 2020 a draft of updated guidance on this topic).

Other FDA-approved agents from the SGLT2 inhibitor class include canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), and all three showed evidence for a statistically significant effect on reducing the incidence of CV disease death and heart failure hospitalizations, as well as renal complications (Can J Diabetes. 2020 Feb;44[1]:61-7). The evidence showing that several SGLT2 drugs have important and consistent effects on endpoints like CV death, heart failure hospitalizations, and renal complications has helped propel this class of agents to the forefront of glycemic control treatments. More recently, one agent from this group, dapagliflozin, also significantly cut the rate of heart failure worsening or CV disease death in patients with heart failure with reduced ejection fraction but without diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). Based on this evidence, the FDA is currently considering adding a new indication for dapagliflozin that would also label it for use in patients with heart failure with reduced ejection fraction but without diabetes.

mzoler@mdedge.com

The sodium-glucose transporter 2 (SGLT-2) inhibitor ertugliflozin broke ranks with the other drugs in its class and failed to produce statistically significant drops in the both the combined incidence of cardiovascular (CV) death or heart failure hospitalization, and the rate of adverse renal outcomes, in the mandated CV outcomes trial run for ertugliflozin with more than 8,200 patients with type 2 diabetes and established CV disease.

Merck, one of the companies that markets the drug, announced the topline results in a quarterly financial report released on April 28, 2020.

According to the report, the results from the ertugliflozin cardiovascular outcomes trial “achieved its primary endpoint of noninferiority for major adverse CV events (MACE), compared to placebo in patients with type 2 diabetes mellitus and established atherosclerotic CV disease,” but “the key secondary endpoints of superiority” of ertugliflozin, compared with placebo, “for time to the composite of CV death or hospitalization for heart failure, CV death alone, and the composite of renal death, dialysis/transplant or doubling of serum creatinine from baseline were not met.”

However, the report added that, “while not a prespecified hypothesis for statistical testing, a reduction in hospitalization for heart failure was observed” with ertugliflozin treatment, and the report further said that the drug’s safety profile in the trial “was consistent with that reported in previous studies.” The statement closed by saying that detailed results from the trial are scheduled to be presented on June 16, 2020, at the virtual American Diabetes Association’s 80th Scientific Sessions.

These results came from the VERTIS CV (Evaluation of Ertugliflozin EffIcacy and Safety Cardiovascular Outcomes) trial, which researchers said in 2018 had administered at least one investigational dose to 8,238 randomized patients at centers in any of 34 countries during two enrollment periods in 2013-2015 and 2016-2017 (Am Heart J. 2018 Dec;206:11-23). The tested agent, ertugliflozin (Steglatro) received Food and Drug Administration marketing approval late in 2017 for the indication of improving glycemic control in patients with type 2 diabetes.

The FDA mandated cardiovascular outcomes trials for new glycemic control drugs in guidance the agency issued in 2008 (the FDA released in March 2020 a draft of updated guidance on this topic).

Other FDA-approved agents from the SGLT2 inhibitor class include canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), and all three showed evidence for a statistically significant effect on reducing the incidence of CV disease death and heart failure hospitalizations, as well as renal complications (Can J Diabetes. 2020 Feb;44[1]:61-7). The evidence showing that several SGLT2 drugs have important and consistent effects on endpoints like CV death, heart failure hospitalizations, and renal complications has helped propel this class of agents to the forefront of glycemic control treatments. More recently, one agent from this group, dapagliflozin, also significantly cut the rate of heart failure worsening or CV disease death in patients with heart failure with reduced ejection fraction but without diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). Based on this evidence, the FDA is currently considering adding a new indication for dapagliflozin that would also label it for use in patients with heart failure with reduced ejection fraction but without diabetes.

mzoler@mdedge.com

The sodium-glucose transporter 2 (SGLT-2) inhibitor ertugliflozin broke ranks with the other drugs in its class and failed to produce statistically significant drops in the both the combined incidence of cardiovascular (CV) death or heart failure hospitalization, and the rate of adverse renal outcomes, in the mandated CV outcomes trial run for ertugliflozin with more than 8,200 patients with type 2 diabetes and established CV disease.

Merck, one of the companies that markets the drug, announced the topline results in a quarterly financial report released on April 28, 2020.

According to the report, the results from the ertugliflozin cardiovascular outcomes trial “achieved its primary endpoint of noninferiority for major adverse CV events (MACE), compared to placebo in patients with type 2 diabetes mellitus and established atherosclerotic CV disease,” but “the key secondary endpoints of superiority” of ertugliflozin, compared with placebo, “for time to the composite of CV death or hospitalization for heart failure, CV death alone, and the composite of renal death, dialysis/transplant or doubling of serum creatinine from baseline were not met.”

However, the report added that, “while not a prespecified hypothesis for statistical testing, a reduction in hospitalization for heart failure was observed” with ertugliflozin treatment, and the report further said that the drug’s safety profile in the trial “was consistent with that reported in previous studies.” The statement closed by saying that detailed results from the trial are scheduled to be presented on June 16, 2020, at the virtual American Diabetes Association’s 80th Scientific Sessions.

These results came from the VERTIS CV (Evaluation of Ertugliflozin EffIcacy and Safety Cardiovascular Outcomes) trial, which researchers said in 2018 had administered at least one investigational dose to 8,238 randomized patients at centers in any of 34 countries during two enrollment periods in 2013-2015 and 2016-2017 (Am Heart J. 2018 Dec;206:11-23). The tested agent, ertugliflozin (Steglatro) received Food and Drug Administration marketing approval late in 2017 for the indication of improving glycemic control in patients with type 2 diabetes.

The FDA mandated cardiovascular outcomes trials for new glycemic control drugs in guidance the agency issued in 2008 (the FDA released in March 2020 a draft of updated guidance on this topic).

Other FDA-approved agents from the SGLT2 inhibitor class include canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), and all three showed evidence for a statistically significant effect on reducing the incidence of CV disease death and heart failure hospitalizations, as well as renal complications (Can J Diabetes. 2020 Feb;44[1]:61-7). The evidence showing that several SGLT2 drugs have important and consistent effects on endpoints like CV death, heart failure hospitalizations, and renal complications has helped propel this class of agents to the forefront of glycemic control treatments. More recently, one agent from this group, dapagliflozin, also significantly cut the rate of heart failure worsening or CV disease death in patients with heart failure with reduced ejection fraction but without diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). Based on this evidence, the FDA is currently considering adding a new indication for dapagliflozin that would also label it for use in patients with heart failure with reduced ejection fraction but without diabetes.

mzoler@mdedge.com

The results of two postapproval studies confirm the potential risk of hyperinflation and acute pancreatitis with the Orbera and ReShape liquid-filled intragastric balloon systems used to treat obesity.

The Orbera Intragastric Balloon System is manufactured by Apollo Endosurgery. The ReShape Integrated Dual Balloon System was previously manufactured by ReShape Medical but was acquired by Apollo Endosurgery in December 2018.

In the Orbera postapproval study, 6 of 258 patients (2.3%) experienced balloon hyperinflation, the Food and Drug Administration said today in a letter to health care providers. There were no hyperinflation events detected in the ReShape postapproval study.

Acute pancreatitis was reported in 2 of 159 patients (1.3%) in the ReShape study, with no cases of acute pancreatitis reported in the Orbera study.

No balloon hyperinflation or acute pancreatitis events were reported in the studies the companies submitted to the FDA to gain approval, the agency said.

No deaths were reported in the postapproval studies, though the agency notes that the studies were not powered to detect. However, since Orbera and ReShape were approved in 2015, the FDA has learned of 18 deaths worldwide, including 8 patients in the United States (5 with Orbera and 3 with ReShape).

The FDA issued previous letters to health care providers concerning issues with these devices in June 2018, August 2017, and February 2017.

As of Jan. 1, 2019, Apollo Endosurgery stopped selling the ReShape Balloon. The Orbera balloon remains available.

“The FDA wants to ensure healthcare professionals are aware of the rates of these potential complications observed in the post-approval studies so they can discuss the risks and benefits of weight loss treatments with patients and monitor patients during treatment,” Benjamin Fisher, PhD, director of the Reproductive, Gastro-Renal, Urological, General Hospital Device, and Human Factors Office at the FDA’s Center for Devices and Radiological Health, said in a statement.

“While these devices remain an appropriate treatment option for some patients with obesity, patients should always discuss with their doctors which treatment option is best for them,” said Dr. Fisher.

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

The results of two postapproval studies confirm the potential risk of hyperinflation and acute pancreatitis with the Orbera and ReShape liquid-filled intragastric balloon systems used to treat obesity.

The Orbera Intragastric Balloon System is manufactured by Apollo Endosurgery. The ReShape Integrated Dual Balloon System was previously manufactured by ReShape Medical but was acquired by Apollo Endosurgery in December 2018.

In the Orbera postapproval study, 6 of 258 patients (2.3%) experienced balloon hyperinflation, the Food and Drug Administration said today in a letter to health care providers. There were no hyperinflation events detected in the ReShape postapproval study.

Acute pancreatitis was reported in 2 of 159 patients (1.3%) in the ReShape study, with no cases of acute pancreatitis reported in the Orbera study.

No balloon hyperinflation or acute pancreatitis events were reported in the studies the companies submitted to the FDA to gain approval, the agency said.

No deaths were reported in the postapproval studies, though the agency notes that the studies were not powered to detect. However, since Orbera and ReShape were approved in 2015, the FDA has learned of 18 deaths worldwide, including 8 patients in the United States (5 with Orbera and 3 with ReShape).

The FDA issued previous letters to health care providers concerning issues with these devices in June 2018, August 2017, and February 2017.

As of Jan. 1, 2019, Apollo Endosurgery stopped selling the ReShape Balloon. The Orbera balloon remains available.

“The FDA wants to ensure healthcare professionals are aware of the rates of these potential complications observed in the post-approval studies so they can discuss the risks and benefits of weight loss treatments with patients and monitor patients during treatment,” Benjamin Fisher, PhD, director of the Reproductive, Gastro-Renal, Urological, General Hospital Device, and Human Factors Office at the FDA’s Center for Devices and Radiological Health, said in a statement.

“While these devices remain an appropriate treatment option for some patients with obesity, patients should always discuss with their doctors which treatment option is best for them,” said Dr. Fisher.

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

The results of two postapproval studies confirm the potential risk of hyperinflation and acute pancreatitis with the Orbera and ReShape liquid-filled intragastric balloon systems used to treat obesity.

The Orbera Intragastric Balloon System is manufactured by Apollo Endosurgery. The ReShape Integrated Dual Balloon System was previously manufactured by ReShape Medical but was acquired by Apollo Endosurgery in December 2018.

In the Orbera postapproval study, 6 of 258 patients (2.3%) experienced balloon hyperinflation, the Food and Drug Administration said today in a letter to health care providers. There were no hyperinflation events detected in the ReShape postapproval study.

Acute pancreatitis was reported in 2 of 159 patients (1.3%) in the ReShape study, with no cases of acute pancreatitis reported in the Orbera study.

No balloon hyperinflation or acute pancreatitis events were reported in the studies the companies submitted to the FDA to gain approval, the agency said.

No deaths were reported in the postapproval studies, though the agency notes that the studies were not powered to detect. However, since Orbera and ReShape were approved in 2015, the FDA has learned of 18 deaths worldwide, including 8 patients in the United States (5 with Orbera and 3 with ReShape).

The FDA issued previous letters to health care providers concerning issues with these devices in June 2018, August 2017, and February 2017.

As of Jan. 1, 2019, Apollo Endosurgery stopped selling the ReShape Balloon. The Orbera balloon remains available.

“The FDA wants to ensure healthcare professionals are aware of the rates of these potential complications observed in the post-approval studies so they can discuss the risks and benefits of weight loss treatments with patients and monitor patients during treatment,” Benjamin Fisher, PhD, director of the Reproductive, Gastro-Renal, Urological, General Hospital Device, and Human Factors Office at the FDA’s Center for Devices and Radiological Health, said in a statement.

“While these devices remain an appropriate treatment option for some patients with obesity, patients should always discuss with their doctors which treatment option is best for them,” said Dr. Fisher.

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

The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”

In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.

“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.

The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.

The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.

The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.

mzoler@mdedge.com

The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”

In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.

“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.

The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.

The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.

The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.

mzoler@mdedge.com

The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”

In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.

“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.

The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.

The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.

The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.

mzoler@mdedge.com

The US Food and Drug Administration (FDA) granted accelerated approval to sacituzumab govitecan (Trodelvy, Immunomedics) for the treatment of metastatic triple-negative breast cancer (TNBC).

Eligible patients must have received at least two prior therapies.

TNBC is so-called because it lacks the three cellular targets present in more common forms of breast cancer. It is usually treated with chemotherapy.

Sacituzumab govitecan offers a new approach – and it has a target.

Given intravenously, the new drug is an antibody-drug conjugate in which SN-38, an active metabolite of the chemotherapy drug irinotecan (multiple brands), is coupled to a monoclonal antibody that targets an antigen that has high expression in TNBC and induces cancer cell growth.

“Metastatic triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options,” observed Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research in a press statement. “There is intense interest in finding new medications” for this patient population, he added.

The new approval is based on safety and efficacy results from a phase 1/2 clinical trial of 108 patients (median age, 56 years) who had received at least two prior treatments for metastatic disease.

The overall response rate was 33% (n = 36), including three complete responses. Median duration of response was 7.7 months. Of responders, 55.6% maintained their response for at least 6 months and 16.7% for at least 12 months.

Median progression-free survival was 5.5 months, and median overall survival was 13.0 months.

The study data were published last year in the New England Journal of Medicine.

“It’s not every day that we see this sort of clinical activity in this aggressive subtype of breast cancer,” said senior study author Kevin Kalinsky, MD, in an interview at that time. He is a medical oncologist at New York–Presbyterian Hospital and Columbia University Medical Center in New York City.

The most common side effects of the new therapy were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash, and abdominal pain.

No peripheral neuropathy of grade 3 or higher was reported.

In the study, patients received sacituzumab govitecan intravenously (10 mg/kg body weight) on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

The 108 participants received a mean 18.7 doses of sacituzumab govitecan, or 9.6 cycles. The median duration of exposure was 5.1 months.

Three patients discontinued treatment because of adverse events, and two patients discontinued because of drug-related events.

The prescribing information includes a boxed warning regarding the risks of severe neutropenia and severe diarrhea. Blood cell counts should be monitored during treatment and granulocyte-colony stimulating factor (G-CSF) therapy should be considered. Anti-infective treatment should be initiated in the event of febrile neutropenia. Patients with reduced uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) activity are at increased risk for neutropenia following initiation of treatment.

The new drug can also cause hypersensitivity reactions including severe anaphylactic reactions.

Women who are pregnant should not take sacituzumab govitecan.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) granted accelerated approval to sacituzumab govitecan (Trodelvy, Immunomedics) for the treatment of metastatic triple-negative breast cancer (TNBC).

Eligible patients must have received at least two prior therapies.

TNBC is so-called because it lacks the three cellular targets present in more common forms of breast cancer. It is usually treated with chemotherapy.

Sacituzumab govitecan offers a new approach – and it has a target.

Given intravenously, the new drug is an antibody-drug conjugate in which SN-38, an active metabolite of the chemotherapy drug irinotecan (multiple brands), is coupled to a monoclonal antibody that targets an antigen that has high expression in TNBC and induces cancer cell growth.

“Metastatic triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options,” observed Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research in a press statement. “There is intense interest in finding new medications” for this patient population, he added.

The new approval is based on safety and efficacy results from a phase 1/2 clinical trial of 108 patients (median age, 56 years) who had received at least two prior treatments for metastatic disease.

The overall response rate was 33% (n = 36), including three complete responses. Median duration of response was 7.7 months. Of responders, 55.6% maintained their response for at least 6 months and 16.7% for at least 12 months.

Median progression-free survival was 5.5 months, and median overall survival was 13.0 months.

The study data were published last year in the New England Journal of Medicine.

“It’s not every day that we see this sort of clinical activity in this aggressive subtype of breast cancer,” said senior study author Kevin Kalinsky, MD, in an interview at that time. He is a medical oncologist at New York–Presbyterian Hospital and Columbia University Medical Center in New York City.

The most common side effects of the new therapy were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash, and abdominal pain.

No peripheral neuropathy of grade 3 or higher was reported.

In the study, patients received sacituzumab govitecan intravenously (10 mg/kg body weight) on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

The 108 participants received a mean 18.7 doses of sacituzumab govitecan, or 9.6 cycles. The median duration of exposure was 5.1 months.

Three patients discontinued treatment because of adverse events, and two patients discontinued because of drug-related events.

The prescribing information includes a boxed warning regarding the risks of severe neutropenia and severe diarrhea. Blood cell counts should be monitored during treatment and granulocyte-colony stimulating factor (G-CSF) therapy should be considered. Anti-infective treatment should be initiated in the event of febrile neutropenia. Patients with reduced uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) activity are at increased risk for neutropenia following initiation of treatment.

The new drug can also cause hypersensitivity reactions including severe anaphylactic reactions.

Women who are pregnant should not take sacituzumab govitecan.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) granted accelerated approval to sacituzumab govitecan (Trodelvy, Immunomedics) for the treatment of metastatic triple-negative breast cancer (TNBC).

Eligible patients must have received at least two prior therapies.

TNBC is so-called because it lacks the three cellular targets present in more common forms of breast cancer. It is usually treated with chemotherapy.

Sacituzumab govitecan offers a new approach – and it has a target.

Given intravenously, the new drug is an antibody-drug conjugate in which SN-38, an active metabolite of the chemotherapy drug irinotecan (multiple brands), is coupled to a monoclonal antibody that targets an antigen that has high expression in TNBC and induces cancer cell growth.

“Metastatic triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options,” observed Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research in a press statement. “There is intense interest in finding new medications” for this patient population, he added.

The new approval is based on safety and efficacy results from a phase 1/2 clinical trial of 108 patients (median age, 56 years) who had received at least two prior treatments for metastatic disease.

The overall response rate was 33% (n = 36), including three complete responses. Median duration of response was 7.7 months. Of responders, 55.6% maintained their response for at least 6 months and 16.7% for at least 12 months.

Median progression-free survival was 5.5 months, and median overall survival was 13.0 months.

The study data were published last year in the New England Journal of Medicine.

“It’s not every day that we see this sort of clinical activity in this aggressive subtype of breast cancer,” said senior study author Kevin Kalinsky, MD, in an interview at that time. He is a medical oncologist at New York–Presbyterian Hospital and Columbia University Medical Center in New York City.

The most common side effects of the new therapy were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash, and abdominal pain.

No peripheral neuropathy of grade 3 or higher was reported.

In the study, patients received sacituzumab govitecan intravenously (10 mg/kg body weight) on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

The 108 participants received a mean 18.7 doses of sacituzumab govitecan, or 9.6 cycles. The median duration of exposure was 5.1 months.

Three patients discontinued treatment because of adverse events, and two patients discontinued because of drug-related events.

The prescribing information includes a boxed warning regarding the risks of severe neutropenia and severe diarrhea. Blood cell counts should be monitored during treatment and granulocyte-colony stimulating factor (G-CSF) therapy should be considered. Anti-infective treatment should be initiated in the event of febrile neutropenia. Patients with reduced uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) activity are at increased risk for neutropenia following initiation of treatment.

The new drug can also cause hypersensitivity reactions including severe anaphylactic reactions.

Women who are pregnant should not take sacituzumab govitecan.

This article first appeared on Medscape.com.

International Laboratories has initiated a voluntary recall to the consumer level in the United States of a single lot of the antiplatelet clopidogrel because it is mislabeled and may contain simvastatin, a cholesterol-lowering drug, instead of clopidogrel.

The recalled product ― lot number 117099A of clopidogrel tablets (USP 75 mg) packaged in bottles of 30 tablets ― may contain clopidogrel 75 mg tablets or it could contain simvastatin tablets (USP 10 mg), according to a company announcement posted on the US Food and Drug Administration (FDA) website.

“Missed doses of clopidogrel increases the risk of heart attack and stroke which can be life threatening. Additionally, unintentional consumption of simvastatin could include the common side effects associated with its use and may cause fetal harm when administered to a pregnant woman,” the company cautions.

To date, the company has not received any reports of harm arising from the problem that prompted the recall.

The recalled product was distributed nationwide and was delivered to distribution centers in Arkansas, Georgia, Indiana, California, and Maryland and to retail stores in all US states.

International Laboratories is notifying distributors and customers by letter and is arranging for the return of all recalled products.

For questions regarding this recall, contact Inmar by phone 855-258-7280 (weekdays between 9:00 AM and 5:00 PM EST) or by email at internationallabs@inmar.com.

Adverse reactions or quality problems experienced with the use of this product should be reported to the FDA’s MedWatch adverse event reporting program.
 

This article first appeared on Medscape.com.

International Laboratories has initiated a voluntary recall to the consumer level in the United States of a single lot of the antiplatelet clopidogrel because it is mislabeled and may contain simvastatin, a cholesterol-lowering drug, instead of clopidogrel.

The recalled product ― lot number 117099A of clopidogrel tablets (USP 75 mg) packaged in bottles of 30 tablets ― may contain clopidogrel 75 mg tablets or it could contain simvastatin tablets (USP 10 mg), according to a company announcement posted on the US Food and Drug Administration (FDA) website.

“Missed doses of clopidogrel increases the risk of heart attack and stroke which can be life threatening. Additionally, unintentional consumption of simvastatin could include the common side effects associated with its use and may cause fetal harm when administered to a pregnant woman,” the company cautions.

To date, the company has not received any reports of harm arising from the problem that prompted the recall.

The recalled product was distributed nationwide and was delivered to distribution centers in Arkansas, Georgia, Indiana, California, and Maryland and to retail stores in all US states.

International Laboratories is notifying distributors and customers by letter and is arranging for the return of all recalled products.

For questions regarding this recall, contact Inmar by phone 855-258-7280 (weekdays between 9:00 AM and 5:00 PM EST) or by email at internationallabs@inmar.com.

Adverse reactions or quality problems experienced with the use of this product should be reported to the FDA’s MedWatch adverse event reporting program.
 

This article first appeared on Medscape.com.

International Laboratories has initiated a voluntary recall to the consumer level in the United States of a single lot of the antiplatelet clopidogrel because it is mislabeled and may contain simvastatin, a cholesterol-lowering drug, instead of clopidogrel.

The recalled product ― lot number 117099A of clopidogrel tablets (USP 75 mg) packaged in bottles of 30 tablets ― may contain clopidogrel 75 mg tablets or it could contain simvastatin tablets (USP 10 mg), according to a company announcement posted on the US Food and Drug Administration (FDA) website.

“Missed doses of clopidogrel increases the risk of heart attack and stroke which can be life threatening. Additionally, unintentional consumption of simvastatin could include the common side effects associated with its use and may cause fetal harm when administered to a pregnant woman,” the company cautions.

To date, the company has not received any reports of harm arising from the problem that prompted the recall.

The recalled product was distributed nationwide and was delivered to distribution centers in Arkansas, Georgia, Indiana, California, and Maryland and to retail stores in all US states.

International Laboratories is notifying distributors and customers by letter and is arranging for the return of all recalled products.

For questions regarding this recall, contact Inmar by phone 855-258-7280 (weekdays between 9:00 AM and 5:00 PM EST) or by email at internationallabs@inmar.com.

Adverse reactions or quality problems experienced with the use of this product should be reported to the FDA’s MedWatch adverse event reporting program.
 

This article first appeared on Medscape.com.