An FDA advisory panel today voted 16-0, with 1 abstention, to recommend approval for semaglutide, a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist from Novo Nordisk. The drug is expected to challenge Eli Lilly & Co’s Trulicity (dulaglutide) for market share after a head-to-head
study showed it gave patients with type 2 diabetes better glycemic control and more weight loss.
As expected, much of the discussion before the Endocrinologic and Metabolic Drugs Advisory Committee was about concerns with retinopathy, after the cardiovascular (CV) outcomes trial for semaglutide (SUSTAIN-6) showed an increase in absolute risk for the eye condition. But those concerns were not repeated in SUSTAIN-7, the subsequent trial that compared the competing GLP-1 receptor agonists.
A briefing document
from FDA released Monday cited trial results that showed semaglutide posed no CV risk and that benefits for reducing glycated hemoglobin (A1C) and weight loss were greater than risks of retinopathy. FDA typically follows recommendations from advisory panels.
"Semaglutide has the potential to impact the lives of people with type 2 diabetes by helping to meaningfully reduce A1C. This treatment option may also help people lose weight," Todd Hobbs, vice president and US chief medical officer of Novo Nordisk said in a statement
after the decision. "We look forward to continuing to work with the FDA as they complete their review of semaglutide."
Key points of the discussion were whether the increased risk in retinopathy complications seen in SUSTAIN-6 were the result of the therapy or the result of the rapid drop in A1C among patients with long-term diabetes. An FDA discussion guide stated that over time, patients with worsening retinopathy will do better by having improved A1C control.
While the study data showed that patients with baseline diabetic retinopathy had a higher absolute risk of complications compared with those who did not have retinopathy at baseline, the relative risk for the 2 groups was similar. However, FDA experts found no causal relationship with semaglutide could be gleaned from the data.
Novo Nordisk officials suggested a warning label, but not a boxed warning, could guide patients who are at risk of complications.
FDA action on semaglutide is expected in early December.
Oral version under study.
The panel meeting comes a day after phase 2 results
published in JAMA
show patients taking a once-a-day pill form of semaglutide achieved A1C and weight loss results comparable to those taking the weekly injectable form now being reviewed by FDA. The study found that 90% of the patients taking a 40 mg dose of the oral drug reached an A1C below the target of 7.0%, compared with 93% of those taking injectable semaglutide and 28% on placebo after 26 weeks. Those taking the oral drug lost an average of 6.9 kg, compared with 6.4 kg for those on the injected drug and 1.2 kg on placebo.