Can Monthly Dosing With Novel GLP-1 Maintain Weight Loss?

At the American Diabetes Association annual meeting, updated phase II data from the VESPER program showed that patients who achieved weight loss with a weekly dose of the ultra-long-acting investigational GLP-1 agonist berobenatide could transition to monthly dosing and maintain that trajectory with favorable gastrointestinal (GI) tolerability.

In this MedPage Today video, John Buse, MD, PhD, of the University of North Carolina School of Medicine at Chapel Hill, discusses what the data suggest about the potential of monthly GLP-1 drug therapy and how crucial tolerability is to achieving efficacy targets in the phase III program.

Following is a transcript of his remarks:

Berobenatide is a GLP-1 receptor agonist. It’s being specifically developed to provide clinically meaningful weight loss at a similar magnitude and with great tolerability as the currently available therapies for overweight and obesity. VESPER-1 was a phase II study that examined various doses. Those results were previously presented at the Obesity Society meeting. And here at the American Diabetes Association meeting, we presented additional data looking at higher doses and alternative dosing strategies.

So what we showed was that berobenatide 2.4 mg weekly demonstrated 16% weight loss at 32 weeks, so very solid efficacy. And in examining monthly dosing as opposed to weekly dosing, the benefits with regard to weight loss seemed to be similar and on track and the adverse event profile looked excellent. So as people transition from weekly dosing to monthly dosing, there was just a small blip in nausea and other GI adverse events and then a great pattern of tolerability.

In general, the GI tolerability was outstanding. There were no severe GI events and the doses examined here will be the doses that are carried forward in the phase III program, specifically the 2.4-mg dose weekly will translate into a 9.6-mg or four times higher dose, but administered monthly. So the same mg of exposure per month but in a monthly dosing program.

I think across all the phase III studies for all the agents being developed in the diabetes and obesity space we have great efficacy and we need to remember that there are a billion people worldwide with obesity and an even larger proportion with overweight. The vast majority of them would have outstanding benefits from 15% weight loss. So I think across these programs, we’re looking at what proportion of patients are able to achieve 10% weight loss and what proportion are able to achieve 15% weight loss or more.

But really built into that is the issue of tolerability, namely that people who don’t tolerate a medication well rarely continue and certainly don’t get to the highest doses. So built into this berobenatide program is an effort to have a very tolerable program of titration and advancing doses to allow that greater degree of weight loss.