Pfizer takes aim at BMS' first-in-class Zeposia with FDA nod for ulcerative colitis drug Velsipity

Bristol Myers Squibb’s Zeposia is no longer the only S1P receptor modulator on the market for ulcerative colitis, thanks to an FDA approval for what appears to be a more effective drug from Pfizer.

The FDA has approved Pfizer’s etrasimod under the brand name Velsipity as an oral, once-daily treatment for adults with moderate to severe active ulcerative colitis, the company said Friday.

The approval marks a validation for Pfizer’s $6.7 billion acquisition of Arena Pharmaceuticals, in which Velsipity served as the centerpiece.

Velsipity is a direct threat to BMS’ Zeposia, which scored its own UC nod in 2021. Pfizer has billed Velsipity as a potential best-in-class option with an attractive clinical profile that doctors are eager to start prescribing.

Leerink Partners analysts last year estimated that Velsipity’s UC sales in the U.S. could reach $1 billion by 2031. For its part, BMS has projected Zeposia could reach global 2030 sales of more than $3 billion in multiple indications.

Velsipity demonstrated better efficacy than Zeposia did in their separate trials, although cross-trial comparisons carry intrinsic problems and are less reliable than head-to-head trials.

In the ELEVATE UC52 trial conducted in UC patients who had failed or couldn’t tolerate at least one conventional therapy, biologic or JAK inhibitor, Velsipity helped 27% of patients achieve remission at week 12, versus about 7% for placebo. The difference in remission rates between the two arms widened to about 25% by one year.

By comparison, Zeposia showed a 19% edge over placebo after one year in its own trial.

When presenting the Velsipity data last year, Pfizer argued that its drug’s efficacy advantage was likely understated compared with Zeposia’s because of different trial designs.

The Velsipity trial used a “treat-through” design, in which patients stick to the treatment they’re randomized to from day 1. The Zeposia study, however, used a rerandomization design, where only patients who responded to Zeposia are rerandomized to either stay with Zeposia or switch to placebo in the maintenance phase.

During an investor call last May, Arena’s etrasimod UC team lead, Sheldon Sloan, said some analyses suggested that the type of design used in the BMS trial could increase the rates of remission by as much as 1.5 times compared with the Pfizer one.

Pfizer has also touted a potential tolerability advantage for Velsipity when it comes to certain cardiovascular side effects. Three cases of treatment discontinuation related to slow heartbeat were reported for Velsipity in the first 12 weeks of its study, although Pfizer said the adverse events weren’t serious.

The Velsipity label includes the same warning about bradyarrhythmia as on Zeposia’s label, forcing patients to undergo an ECG test before starting treatment. But unlike Zeposia, Velsipity doesn’t require dosing titration.

Both Pfizer and BMS are looking to expand their S1P drugs to other autoimmune diseases, including the other form of inflammatory bowel disease, Crohn’s disease.

It’s not just Zeposia that Pfizer is targeting. Velsipity’s 32% remission rate after one year is on par with some of the biologics out there. Pfizer argued that Velsipity deserves a place as a front-line novel treatment right after traditional 5-ASA therapies or steroids.