FDA panel backs diabetes drug for weight loss indication

A diabetes drug is now poised to become a weight loss therapeutic, even in patients without the condition, after a panel of Food and Drug Administration advisers recommended approval of liraglutide for weight management.

The glucagon-like peptide-1 receptor agonist, to be marketed as Saxenda by Novo Nordisk, has been on the market since 2010 for treatment of type 2 diabetes under the brand name Victoza. The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 14-1 that Saxenda is safe and effective and should be approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of at least 30 kg/m², or 27 kg/m² with at least one weight-related comorbidity.

Liraglutide is marketed at a lower dose for diabetes – a 1.8-mg, once-daily dose that’s delivered subcutaneously through a pen-like device – than that proposed for weight management, which would be a 3-mg dose delivered the same way.

The vote to approve came despite the fact that even the lower dose of liraglutide currently carries a boxed warning about the potential for medullary thyroid (C-cell) tumors, and includes warnings and precautions about the potential for pancreatitis, serious hypoglycemia, renal impairment, and hypersensitivity. There also have been significant adverse events in clinical trials and reported to the FDA since the drug has been on the market, including nausea and vomiting and increases in heart rate.

In the phase III studies of Saxenda – which included more than 3,000 patients who took the drug – there were 48 cancers detected, including 7 C-cell thyroid tumors and 14 breast neoplasms.

The panel discussed at length whether the 3-mg dose may trigger more tumors or spur a greater incidence of other side effects, especially since the anticipated wider use may expose even more patients to the drug’s downsides.

Fourteen of the committee members put aside their concerns and voted for approval, but it was not cut-and-dried for all of them.

“For me it was more of a difficult decision rendering an opinion on the risk-benefit ratio,” said Dr. Kenneth Burman, acting chairperson of the committee.

He said he was not completely convinced that the risk for medullary thyroid tumors was minimal. Dr. Burman, director of the endocrine section at the Washington Hospital Center, also said that he was concerned that there was no real guidance on how long a patient should take liraglutide for weight management, especially if the effect plateaued as it did in trials, or was reversed.

Medullary tumors are rare in the general population, and though rare in the phase III clinical trials in 3-mg liraglutide, the data still suggested the possibility of an increased risk, said FDA reviewers. There was also a small excess risk of breast cancers in those trials, which suggested a potential signal, said Christian Hampp, Ph.D., a reviewer from the epidemiology division at the FDA’s Center for Drug Evaluation and Research.

However, Dr. Julie Golden, a medical officer in the FDA’s division of metabolism and endocrinology products, noted that there’s little evidence to suggest that liraglutide has a role in promoting breast cancer.

Panelist Barbara Hansen, Ph.D., agreed that there seemed to be little biological plausibility. “I’m happy with the amount of risk that has been identified,” said Dr. Hansen, professor of internal medicine, University of South Florida College of Medicine, Tampa. “I don’t see a signal there,” she said.

The majority of the committee agreed that liraglutide was effective for weight loss and met the FDA criteria, which was a 5% difference in mean weight loss between the drug and placebo; or at least 35% of patients on therapy losing at least 5% of their baseline weight and double the number on placebo who lost that much; and, improvement in cardiometabolic parameters.

More than 5,000 patients were enrolled in the four phase III trials; over 3,000 took the 3-mg dose of liraglutide. All patients were required to have a stable body weight and to have failed previous dietary intervention. Once in the study, they were told to reduce caloric intake by 500 kcal a day and to maintain or add at least 150 minutes week of physical activity.

The mean age was 47 years, and most participants were women. The mean BMI was 38 kg/m².

In the largest trial, 3,731 patients were studied for 56 weeks, and were stratified by the presence or absence of prediabetes. Of patients taking liraglutide, 64% lost at least 5% of their body weight and 33% lost at least 10%, compared with 27% and 10% of the placebo patients, respectively. There were no significant differences in these endpoints between patients with prediabetes and those without.

Results were similar across the three other phase III studies, though not as pronounced. In addition, Novo Nordisk said that weight loss began to plateau for many patients at 34 weeks. Although liraglutide also helped reduce hypertension, blood lipids, blood glucose, and waist circumference, there were still signs that it might have some adverse cardiovascular effects.

Many panel members said they’d like to see more specific study of cardiovascular outcomes in patients taking a 3-mg dose.

Earlier this week, the FDA approved a combination drug, Contrave (naltrexone and bupropion) for weight management. If approved, Saxenda would be the fourth weight management drug on the U.S. market, after Contrave, the phentermine/topiramate combo Qsymia, and lorcaserin (Belviq).

The FDA is not bound by its advisory panels’ advice, but usually follows their recommendations.

aault@frontlinemedcom.com

On Twitter @aliciaault

A diabetes drug is now poised to become a weight loss therapeutic, even in patients without the condition, after a panel of Food and Drug Administration advisers recommended approval of liraglutide for weight management.

The glucagon-like peptide-1 receptor agonist, to be marketed as Saxenda by Novo Nordisk, has been on the market since 2010 for treatment of type 2 diabetes under the brand name Victoza. The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 14-1 that Saxenda is safe and effective and should be approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of at least 30 kg/m², or 27 kg/m² with at least one weight-related comorbidity.

Liraglutide is marketed at a lower dose for diabetes – a 1.8-mg, once-daily dose that’s delivered subcutaneously through a pen-like device – than that proposed for weight management, which would be a 3-mg dose delivered the same way.

The vote to approve came despite the fact that even the lower dose of liraglutide currently carries a boxed warning about the potential for medullary thyroid (C-cell) tumors, and includes warnings and precautions about the potential for pancreatitis, serious hypoglycemia, renal impairment, and hypersensitivity. There also have been significant adverse events in clinical trials and reported to the FDA since the drug has been on the market, including nausea and vomiting and increases in heart rate.

In the phase III studies of Saxenda – which included more than 3,000 patients who took the drug – there were 48 cancers detected, including 7 C-cell thyroid tumors and 14 breast neoplasms.

The panel discussed at length whether the 3-mg dose may trigger more tumors or spur a greater incidence of other side effects, especially since the anticipated wider use may expose even more patients to the drug’s downsides.

Fourteen of the committee members put aside their concerns and voted for approval, but it was not cut-and-dried for all of them.

“For me it was more of a difficult decision rendering an opinion on the risk-benefit ratio,” said Dr. Kenneth Burman, acting chairperson of the committee.

He said he was not completely convinced that the risk for medullary thyroid tumors was minimal. Dr. Burman, director of the endocrine section at the Washington Hospital Center, also said that he was concerned that there was no real guidance on how long a patient should take liraglutide for weight management, especially if the effect plateaued as it did in trials, or was reversed.

Medullary tumors are rare in the general population, and though rare in the phase III clinical trials in 3-mg liraglutide, the data still suggested the possibility of an increased risk, said FDA reviewers. There was also a small excess risk of breast cancers in those trials, which suggested a potential signal, said Christian Hampp, Ph.D., a reviewer from the epidemiology division at the FDA’s Center for Drug Evaluation and Research.

However, Dr. Julie Golden, a medical officer in the FDA’s division of metabolism and endocrinology products, noted that there’s little evidence to suggest that liraglutide has a role in promoting breast cancer.

Panelist Barbara Hansen, Ph.D., agreed that there seemed to be little biological plausibility. “I’m happy with the amount of risk that has been identified,” said Dr. Hansen, professor of internal medicine, University of South Florida College of Medicine, Tampa. “I don’t see a signal there,” she said.

The majority of the committee agreed that liraglutide was effective for weight loss and met the FDA criteria, which was a 5% difference in mean weight loss between the drug and placebo; or at least 35% of patients on therapy losing at least 5% of their baseline weight and double the number on placebo who lost that much; and, improvement in cardiometabolic parameters.

More than 5,000 patients were enrolled in the four phase III trials; over 3,000 took the 3-mg dose of liraglutide. All patients were required to have a stable body weight and to have failed previous dietary intervention. Once in the study, they were told to reduce caloric intake by 500 kcal a day and to maintain or add at least 150 minutes week of physical activity.

The mean age was 47 years, and most participants were women. The mean BMI was 38 kg/m².

In the largest trial, 3,731 patients were studied for 56 weeks, and were stratified by the presence or absence of prediabetes. Of patients taking liraglutide, 64% lost at least 5% of their body weight and 33% lost at least 10%, compared with 27% and 10% of the placebo patients, respectively. There were no significant differences in these endpoints between patients with prediabetes and those without.

Results were similar across the three other phase III studies, though not as pronounced. In addition, Novo Nordisk said that weight loss began to plateau for many patients at 34 weeks. Although liraglutide also helped reduce hypertension, blood lipids, blood glucose, and waist circumference, there were still signs that it might have some adverse cardiovascular effects.

Many panel members said they’d like to see more specific study of cardiovascular outcomes in patients taking a 3-mg dose.

Earlier this week, the FDA approved a combination drug, Contrave (naltrexone and bupropion) for weight management. If approved, Saxenda would be the fourth weight management drug on the U.S. market, after Contrave, the phentermine/topiramate combo Qsymia, and lorcaserin (Belviq).

The FDA is not bound by its advisory panels’ advice, but usually follows their recommendations.

aault@frontlinemedcom.com

On Twitter @aliciaault

A diabetes drug is now poised to become a weight loss therapeutic, even in patients without the condition, after a panel of Food and Drug Administration advisers recommended approval of liraglutide for weight management.

The glucagon-like peptide-1 receptor agonist, to be marketed as Saxenda by Novo Nordisk, has been on the market since 2010 for treatment of type 2 diabetes under the brand name Victoza. The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 14-1 that Saxenda is safe and effective and should be approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of at least 30 kg/m², or 27 kg/m² with at least one weight-related comorbidity.

Liraglutide is marketed at a lower dose for diabetes – a 1.8-mg, once-daily dose that’s delivered subcutaneously through a pen-like device – than that proposed for weight management, which would be a 3-mg dose delivered the same way.

The vote to approve came despite the fact that even the lower dose of liraglutide currently carries a boxed warning about the potential for medullary thyroid (C-cell) tumors, and includes warnings and precautions about the potential for pancreatitis, serious hypoglycemia, renal impairment, and hypersensitivity. There also have been significant adverse events in clinical trials and reported to the FDA since the drug has been on the market, including nausea and vomiting and increases in heart rate.

In the phase III studies of Saxenda – which included more than 3,000 patients who took the drug – there were 48 cancers detected, including 7 C-cell thyroid tumors and 14 breast neoplasms.

The panel discussed at length whether the 3-mg dose may trigger more tumors or spur a greater incidence of other side effects, especially since the anticipated wider use may expose even more patients to the drug’s downsides.

Fourteen of the committee members put aside their concerns and voted for approval, but it was not cut-and-dried for all of them.

“For me it was more of a difficult decision rendering an opinion on the risk-benefit ratio,” said Dr. Kenneth Burman, acting chairperson of the committee.

He said he was not completely convinced that the risk for medullary thyroid tumors was minimal. Dr. Burman, director of the endocrine section at the Washington Hospital Center, also said that he was concerned that there was no real guidance on how long a patient should take liraglutide for weight management, especially if the effect plateaued as it did in trials, or was reversed.

Medullary tumors are rare in the general population, and though rare in the phase III clinical trials in 3-mg liraglutide, the data still suggested the possibility of an increased risk, said FDA reviewers. There was also a small excess risk of breast cancers in those trials, which suggested a potential signal, said Christian Hampp, Ph.D., a reviewer from the epidemiology division at the FDA’s Center for Drug Evaluation and Research.

However, Dr. Julie Golden, a medical officer in the FDA’s division of metabolism and endocrinology products, noted that there’s little evidence to suggest that liraglutide has a role in promoting breast cancer.

Panelist Barbara Hansen, Ph.D., agreed that there seemed to be little biological plausibility. “I’m happy with the amount of risk that has been identified,” said Dr. Hansen, professor of internal medicine, University of South Florida College of Medicine, Tampa. “I don’t see a signal there,” she said.

The majority of the committee agreed that liraglutide was effective for weight loss and met the FDA criteria, which was a 5% difference in mean weight loss between the drug and placebo; or at least 35% of patients on therapy losing at least 5% of their baseline weight and double the number on placebo who lost that much; and, improvement in cardiometabolic parameters.

More than 5,000 patients were enrolled in the four phase III trials; over 3,000 took the 3-mg dose of liraglutide. All patients were required to have a stable body weight and to have failed previous dietary intervention. Once in the study, they were told to reduce caloric intake by 500 kcal a day and to maintain or add at least 150 minutes week of physical activity.

The mean age was 47 years, and most participants were women. The mean BMI was 38 kg/m².

In the largest trial, 3,731 patients were studied for 56 weeks, and were stratified by the presence or absence of prediabetes. Of patients taking liraglutide, 64% lost at least 5% of their body weight and 33% lost at least 10%, compared with 27% and 10% of the placebo patients, respectively. There were no significant differences in these endpoints between patients with prediabetes and those without.

Results were similar across the three other phase III studies, though not as pronounced. In addition, Novo Nordisk said that weight loss began to plateau for many patients at 34 weeks. Although liraglutide also helped reduce hypertension, blood lipids, blood glucose, and waist circumference, there were still signs that it might have some adverse cardiovascular effects.

Many panel members said they’d like to see more specific study of cardiovascular outcomes in patients taking a 3-mg dose.

Earlier this week, the FDA approved a combination drug, Contrave (naltrexone and bupropion) for weight management. If approved, Saxenda would be the fourth weight management drug on the U.S. market, after Contrave, the phentermine/topiramate combo Qsymia, and lorcaserin (Belviq).

The FDA is not bound by its advisory panels’ advice, but usually follows their recommendations.

aault@frontlinemedcom.com

On Twitter @aliciaault