It's not often that a drug company alerts the media to FDA review documents (PDF) filed ahead of an agency advisory panel hearing. But Novo Nordisk did just that Monday as the Danish drugmaker faces questioning about semaglutide, its key follow-up to blockbuster GLP-1 diabetes drug Victoza.
A weekly GLP-1 injection, semaglutide is Novo's answer to the long-acting GLP-1 medications already on the market, particularly Eli Lilly's Trulicity, which has been siphoning off market share from the long-dominant Victoza. Flagging the FDA documents could be a sign of Novo's confidence in the drug—and the FDA reviewers' apparently positive take.
That's not to say the agency doesn't have some pointed questions for the Endocrinologic and Metabolic Drugs Advisory Committee, however, including safety flags—and potential heart benefits—that cropped up in an outcomes trial.
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Novo contends that semaglutide is a best-in-class medication, and part of its submission to the FDA for approval is that two-year cardiovascular outcomes trial, Sustain-6, which suggested semaglutide could benefit diabetes patients' heart health. The benefits appear to be greatest in stroke prevention at this point, though Novo has mounted a larger outcomes trial that will track CV effects over a longer period of time.
That same trial, however, turned up some numbers showing that more patients in the semaglutide arm suffered complications of diabetic retinopathy, a potentially vision-robbing condition triggered by abnormal blood sugar fluctuations. The number of semaglutide patients who suffered several of complications was more than double those on placebo.
These two sets of numbers appear to be at the center of the FDA staff's questions for the panel, which meets Wednesday. The staff reviewers have asked panel experts to sift the retinopathy data to determine whether trial design or patient enrollment may have caused the discrepancy.
They also asked whether quick lowering of blood sugar with a GLP-1 drug could have been behind the increase in retinopathy complications, and semaglutide did deliver some dramatic improvements in A1C, a common measure of blood sugar levels. Novo has suggested those sudden changes as a culprit.
But analysts largely agree with Novo on semaglutide's promise, even after the potential eye safety questions arose. That's partly because of the data semaglutide continues to put up from ongoing studies. After Sustain-6 appeared, semaglutide beat Trulicity in a head-to-head trial, boosting its prospects when and if it can make its market debut.
Evercore ISI analyst Umer Raffat deemed the Sustain-7 trial results as a “best-case outcome for Novo,” not only for the performance on the efficacy side, but for its side effects numbers. An imbalance in retinopathy cases cropped up in a previous semaglutide trial, but in comparison with Trulicity, the retinopathy cases was “low and comparable” in both arms of the study, Raffat noted.
Plus, the blood glucose beat and weight loss advantage joins another differentiating factor for semaglutide: Proven cardiovascular benefits. The drugmaker is running a larger outcomes trial to confirm the size of that benefit, but Trulicity has yet to post CV risk-reduction data, and those benefits don’t appear to apply to the entire class; two other medications in the field, AstraZeneca’s Bydureon and Sanofi’s Lyxumia, failed to deliver CV benefits in their own outcomes trials, but did prove safe for the heart.
“Novo will now be in a strong position when discussing semaglutide with payers, having demonstrated superiority vs. the competition and also the added CV benefit, which Lilly has yet to do,” Gal noted. His firm sees semaglutide as the GLP market leader by 2025.