Investors are unimpressed by Ventyx Biosciences’ bid to challenge Bristol Myers Squibb and Pfizer for the ulcerative colitis market. While the phase 2 trial hit its primary endpoint, it appears that doubts about whether the drug candidate has an edge over the rival S1P1 modulators etrasimod and Zeposia sent Ventyx’s stock down.
In January, Ventyx discussed the target profile for VTX002, setting out its goal of achieving a 15% to 25% rate of placebo-adjusted clinical remission and a reduction in absolute lymphocyte count (ALC) that would set its candidate apart from the competition. Ventyx identified a 50% ALC reduction as the current standard and expressed hopes that VTX002 could achieve a roughly 70% decline.
The high dose just about fell in the target range, delivering a 17% placebo-adjusted clinical remission rate at Week 13 and a 67% to 68% reduction in ALC from baseline from Week 1 onward. There is daylight between the ALC reductions linked to VTX002 and the rival S1P1 drugs, but the remission rates are closer. Pfizer's etrasimod achieved a 20% reduction in one phase 3 clinical trial, although the figures for a second study, 10%, and the 12% in a trial of BMS' Zeposia were less impressive.
Ventyx latched onto the placebo-adjusted rate of complete endoscopic reduction, 22%, as evidence that its candidate is differentiated, presenting a comparison that showed other ulcerative colitis drugs achieved declines of 3% to 16%. The other S1P1 drugs achieved reductions of 3% to 10%.
The safety profile looks fairly clean, with 16% of patients on the higher dose suffering an adverse event related to the study drug and 4% dropping out as a result of the side effects. No patients had a serious adverse event related to the study drug.
Ventyx called the efficacy “highly differentiated” and the safety profile “excellent,” leading it to conclude that the results support further development. Investors appeared to be less enamored with the data, and possibly with the prospect of bankrolling phase 3 development of a late-to-market candidate, sending the biotech's shares down 19% to $24.40 in premarket trading Tuesday.
The company is lagging behind the front-runners in the S1P1 space. BMS won FDA approval for Zeposia in ulcerative colitis in May 2021, and Pfizer is closing in on the authorization of etrasimod. The S1P1 drugs face competition from molecules that hit a range of other targets such as JAK and TL1A.