An unscheduled Stop

Pfizer Hits a Speedbump with Danuglipron

Dozens of new obesity medicines are in the pipeline for clinical development. Some folks are especially interested in oral medicines that are small molecules. They’re looking for something that offers a sharp contrast with the complex peptide molecules (like semaglutide) given by injection, which are expensive and hard to make. One of the small, orally administered molecules in research is danuglipron (from Pfizer) – but yesterday it hit a speedbump.

We would give the reporting on this twist of events a grade of C for now. Axios says Pfizer is “pulling the plug.” Reuters described Pfizer as “dropping” it, while Fierce Biotech said they were “canning it.” Dramatic headlines get the clicks.

But the real story is that Pfizer is shifting its focus to a once daily formulation of this drug. Not canning, dropping, or pulling plug on danuglipron.

The Problem: Too Many People Stopped

The problem that generated those headlines was quite simple. More than half of the people on danuglipron stopped taking it twice daily in a mid-phase study. That compares to 40 percent that stopped taking a twice daily placebo.

The 40 percent discontinuation of placebo patients is a reminder many different factors can cause people to stop taking a drug. Not just the safety profile of the drug. One of those factors is a regimen that is too much trouble – like taking a drug twice a day, every day.

A Cloudy Future for Oral Options

Clearly this is a cause for caution about danuglipron’s future. It might be a sign of more troubles ahead. Or the once daily formulation might have clear sailing.

But we do note that, compared to Ozempic, Rybelsus has had a relatively slow start. It is a once-daily tablet form of the semaglutide in Ozempic (a once-weekly injection). Sales of Ozempic are five times higher than Rybelsus.

Novo Nordisk has said they plan to seek FDA approval for high-dose oral semaglutide in obesity, submitting an application this year. Lilly has published impressive results with a small molecule for oral administration – orforglipron.

Any of these new oral options might sail to success. Or they might all yield nothing but disappointment. Right now, the future is quite interesting for oral obesity medicines, but cloudy.

Click here for the details from Pfizer on their decision, here, here, and here for further reporting.

An Unscheduled Stop, painting by Charles M. Russell / WikiArt

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December 2, 2023