Abivax delivers Phase 3 ulcerative colitis win, but safety concerns trigger market sell-off
Parisian Abivax shared positive topline results for its Phase 3 trial in ulcerative colitis. Its investigational oral, first-in-class miR-124 enhancer, dubbed obefazimod, met all primary and secondary endpoints, yet investors reacted negatively.
Despite what some described as “the best placebo-adjusted clinical remission rates ever for a large Phase 3 study in ulcerative colitis,” analysts focused on emerging safety questions, including reported malignancy cases observed during the trial, sending the company’s shares sharply lower as investors reassessed the overall risk–benefit profile.
A historic win for remission
The global, randomized, double-blind, placebo-controlled maintenance trial, ABTECT, enrolled 580 individuals who had responded to induction treatment and evaluated once-daily oral obefazimod at 25 mg and 50 mg doses. At Week 44 (end of trial), both doses met the FDA primary endpoint of clinical remission, with remission rates of 50.8% and 51.3%, respectively, compared with 10.4% for placebo. Placebo-adjusted remission rates reached 39.3% and 40.3%, both highly statistically significant.
Abivax’ obefazimod also met all key secondary endpoints, including endoscopic improvement, endoscopic remission, histologic-endoscopic mucosal improvement (HEMI), corticosteroid-free clinical remission and sustained clinical remission. The company CEO, Marc de Garidel, described the data as “landmark Phase 3 results” that highlight “the exceptional potential of obefazimod to redefine the treatment landscape for ulcerative colitis,” but investors were not convinced.
Why investors panicked
While the company stated that obefazimod maintained a “favorable safety profile” with “no new safety signals,” several malignancies were reported during the study. In the 50 mg treatment arm, investigators recorded one case each of prostate cancer, breast cancer, and colonic dysplasia, corresponding to an incidence of 0.5% per event. Non-melanoma skin cancers were also observed, including two cases each of basal cell carcinoma and squamous cell carcinoma in the 50 mg group, and one squamous cell carcinoma case in the 25 mg cohort, although one case of basal cell carcinoma was also reported in the placebo group.
Abivax emphasized that trial investigators considered the prostate, breast, and colonic malignancies unrelated to treatment and noted the absence of organ-specific clustering, suggesting perhaps a pattern more consistent with background incidence than a drug-related signal. The company also highlighted that patients who developed non-melanoma skin cancers were substantially older than the overall study population and frequently carried pre-existing risk factors. However, these safety observations were sufficient to prompt a more cautious tone from investors and analysts.
Jefferies downgraded the stock after the data release, arguing that the malignancy findings could complicate the commercial narrative around obefazimod even if regulators ultimately agree that the cases were unrelated to treatment. According to the bank, the presence of multiple cancer diagnoses in a late-stage trial could weigh on physician adoption, strategic partnering opportunities, and long-term market penetration.
Still on track: the road to FDA approval
Against this backdrop, obefazimod’s mechanism of action differs from currently approved therapies. By enhancing the expression of microRNA-124, a natural regulator of inflammatory pathways, the drug aims to modulate immune responses rather than directly block a single cytokine or receptor. David T. Rubin, M.D., director of the Inflammatory Bowel Disease Center at the University of Chicago Medicine, commented in the company’s press release that the novel mechanism of obefazimod, its ability to induce sustained clinical remission, and its overall long-term safety profile highlight its potential to address a significant unmet need in ulcerative colitis.
The company remains on track for an FDA submission before year-end, and topline results of Phase 2b induction trial for Crohn’s disease are expected mid-year 2027.
