The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 14-1 to recommend approval of liraglutide for chronic weight management in obese and certain overweight patients.
Novo Nordisk is seeking approval for once-daily, injectable liraglutide 3 mg as an adjunct to diet and exercise in patients with a BMI of at least 30 or in those with a BMI of at least 27 and one or more weight-related comorbidities. The proposed trade name is Saxenda.
“I thought the data very clearly supported efficacy in terms of weight loss, at least in a very large subset of patients taking [liraglutide],” committee member David W. Cooke, MD, of Johns Hopkins School of Medicine, said during the meeting.
“I’m less confident in the long-term health benefits, but since the safety data didn’t raise any marked new concerns beyond what’s already been considered for the marketed dosage, it’s reasonable to have liraglutide as a weight loss drug.”
Assessing the Evidence
Novo Nordisk, the drug’s manufacturer, opted to submit the new drug application for the 3.0-mg dose of liraglutide based on results from a dose-ranging phase 2 trial (1807). In the trial, weight change after treatment with liraglutide 1.2 mg, 1.8 mg, 2.4 mg and 3.0 mg, as compared with orlistat and placebo, was evaluated at 20 and 52 weeks.
In addition to trial 1807, results from three individual phase 3 trials (1839, 1922 and 1923) and a phase 3 32-week sleep apnea trial (3970), which, all told, included more than 5,000 patients, were assessed by the FDA. The largest trial was 1839 and therefore had the most influence on data from the pooled analysis, according to the agency.
Results from the FDA analysis indicated that the proportion of patients across all trials who lost at least 5% of their body weight with liraglutide 3.0 mg was significantly higher than with placebo (60.3% vs. 20.4%). Similar results were noted for those who lost at least 10% of their body weight (31.2% vs. 8.7%), according to briefing documents provided by the FDA.
In an analysis of the largest trial, patients taking liraglutide 3.0 mg lost an average of 8% of their baseline body weight, whereas patients on placebo lost only 2.6% by week 56, translating to a mean treatment difference of 5.39%.
The FDA, however, also conducted another analysis that included retrieved dropouts and found treatment differences of 4.6% and 4.8%. These findings countered the sponsor’s contention that patients who dropped out would not affect the results.