Abivax has raised the efficacy bar in ulcerative colitis, linking obefazimod to a 40%, placebo-adjusted jump in clinical remission rates in a phase 3 trial. But the share price of the biotech, a reported takeover target for several Big Pharmas, collapsed after several patients on the high dose developed cancers.
Paris-based Abivax emerged as a top M&A target last year, with AstraZeneca and Eli Lilly reportedly among the companies interested in a deal that could be worth $18 billion, after reporting eight-week data from a phase 3 trial of obefazimod. The data suggested the small molecule, which upregulates miR-124 in immune cells, could disrupt the huge, highly competitive inflammatory bowel disease market.
With Abivax, which has indicated an interest in partnering obefazimod outside the U.S., waiting for the 48-week data before pursuing a deal, the maintenance readout has emerged as a key moment for the biotech and its suitors. Investors, primed for strong efficacy results, reacted badly to the data.
The 25 mg and 50 mg once-daily obefazimod doses performed significantly better than placebo, hitting clinical remission rates of 50.8% and 51.3%, respectively, at Week 44 versus 10.4% in the control arm. At 39.3% and 40.3%, the placebo-adjusted clinical remission rates are below the 48% Abivax reported at Week 48 of its phase 2 open-label extension study but above the bar set by existing oral and biologic treatments.
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Per Abivax’s presentation (PDF), the 39% placebo-adjusted clinical remission maintenance rate after 52 weeks on AbbVie’s oral JAK inhibitor Rinvoq is the only comparable result, with the caveat that cross-trial comparisons can be unreliable. Pfizer’s Velsipity is the next closest challenger, with a placebo-adjusted clinical remission rate of 32%.
Abivax achieved the efficacy in a population with many patients who were refractory to multiple other lines of therapy. About 40% of patients had tried advanced therapy before joining the trial. Talking on an Abivax call about how to compare the data, David Rubin, M.D., a gastroenterologist at the University of Chicago, questioned how many patients in the other studies were refractory to multiple drugs.
Rinvoq’s label has (PDF) a boxed warning with five safety warnings, including a higher rate of all-cause mortality. The phase 3 data suggest obefazimod is free from many of the safety problems associated with AbbVie’s drug. Abivax reported placebo-like infection rates and numerically more treatment emergent adverse events leading to discontinuations on placebo than on either obefazimod dose.
However, there was one case each of prostate cancer, breast cancer and colonic dysplasia on the high dose, compared to zero cases on the low dose or placebo. Abivax also reported two cases each of basal and squamous cell carcinoma on the high dose. There was one case of basal cell carcinoma on placebo and one case of squamous cell carcinoma on the low dose.
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The cancer cases may explain why Abivax’s share price fell about 28% to $92.80 in premarket trading. Yet Rubin, echoing points made by Abivax executives, said the cancer cases are “not worrisome,” adding that “there’s no signal.” Chris Rabbat, Ph.D., global head of medical affairs at Abivax, said the findings observed “are well within the range of what could be expected” for the patient population.
Abivax plans to file for FDA approval toward the end of the year. The biotech expects to publish phase 2b induction data in Crohn’s disease in mid-2027. Rubin said he “fully” expects obefazimod’s mechanism to work in Crohn’s.
