Abivax announced positive topline results from Part 2 of the phase 3 ABTECT maintenance trial evaluating obefazimod in ulcerative colitis (UC), showing clinically meaningful efficacy through week 44 in patients who did not initially respond to induction therapy.

The data build on positive Part 1 topline results announced in early June, when both the 25 mg and 50 mg doses of obefazimod met the primary endpoint of clinical remission and all key secondary endpoints.

Remo Panaccione, MD, professor of medicine and director of the IBD Clinic at the University of Calgary, discussed the ABTECT maintenance program, obefazimod's safety profile, and where the drug could fit into an increasingly crowded UC treatment landscape in an interview with HCPLive.

Part 2 Builds on Part 1's Placebo-Adjusted Efficacy

In Part 2 of the maintenance trial, patients receiving continuous treatment with the 50 mg dose achieved the strongest outcomes across key clinical and endoscopic endpoints, further strengthening obefazimod's benefit-risk profile ahead of the company's planned new drug application (NDA) submission in the fourth quarter of 2026. The long-term safety profile remained consistent with previous studies, with no new safety signals observed.

Part 1 of the maintenance study included 580 patients who had initially responded to induction therapy and then entered the randomized, placebo-controlled maintenance study. Part 2 enrolled an additional 633 patients who had either not responded during induction or had subsequently lost response during maintenance, a population that included the largest cohort of patients with an inadequate response to a JAK inhibitor studied in a phase 3 UC trial to date.

Key results at week 44 include:

• Both the 25 mg and 50 mg doses met the primary endpoint of clinical remission, with remission rates of approximately 51% with either active dose compared with 10% with placebo, a 40-point placebo-adjusted difference
• Endoscopic remission, defined as a Mayo endoscopy score of 0 or 1 among patients who entered the trial with a score of 2 or 3, was achieved by 41.5% of patients on 25 mg and 47.7% of patients on 50 mg, compared with 10% on placebo
• Both doses also met all key secondary endpoints, including endoscopic improvement, histologic-endoscopic mucosal improvement, and steroid-free remission
• Among initial non-responders who continued on the 50 mg dose, about 37% achieved clinical remission and more than 60% achieved response
• Among patients who relapsed on the 25 mg dose during maintenance and were escalated to 50 mg, clinical remission was recaptured in about 56%

Q&A: Remo Panaccione, MD, on the ABTECT Maintenance Program

You've had the opportunity to review the complete ABTECT maintenance program. What do you see as the biggest takeaway for clinicians treating patients with moderate to severe ulcerative colitis?

Before we talk about the maintenance part, it's important to recognize that these results are building upon very impressive induction data, where we saw placebo-adjusted treatment differences for the primary endpoint of clinical remission that were quite substantial. Importantly, the onset of benefit of this drug, which is a once-a-day oral, was rapid, with separation from placebo as early as week one for symptomatic response and week two for symptomatic remission.

Moving into the maintenance part, there are several takeaways. First, this is a very large, clinically relevant program. Part one of the maintenance study included 580 patients who had initially responded to induction and then entered the randomized, placebo-controlled maintenance study. Part two included an additional 633 patients who had either not responded during induction or had subsequently lost response during maintenance.

It's also important for clinicians to recognize that this study included a substantial portion of patients who were difficult to treat. In particular, it enrolled the largest cohort of patients with an inadequate response to a JAK inhibitor that we've ever studied in a phase 3 clinical trial. That's particularly important because JAK inhibitor use tends to be later-line therapy, and we know those patients don't respond as well as naive patients or patients exposed only to monoclonal antibodies.

In part one, there were two maintenance doses, 25 mg and 50 mg, and both met the primary endpoint of clinical remission at week 44. Remission rates were quite high, approximately 51% with either active dose compared to only 10% with placebo. That 40-point difference is the largest placebo-adjusted difference we've seen in a phase 3 trial. Part of that may be due to the placebo rate being quite low, which usually reflects a difficult-to-treat patient population.

In part two, among initial non-responders who continued on 50 mg, about 37% achieved remission and over 60% achieved response. Among patients who relapsed on 25 mg during maintenance and were escalated to 50 mg, clinical remission was recaptured in about 56%.

The most compelling data, though, is the objective data, endoscopic and histologic. All patients entered the trial with a Mayo endoscopy score of 2 or 3, moderate to severe endoscopic inflammation, and needed to reach a score of 0 or 1 to achieve remission. In part one, endoscopic remission was 41.5% with 25 mg and 47.7% with 50 mg, compared to only 10% with placebo. These are among the strongest endoscopic remission results we've seen in a phase 3 program. Both doses also met all key secondary endpoints, including endoscopic improvement, histologic-endoscopic mucosal improvement, and steroid-free remission. And over 44 weeks, we didn't see any safety signals that were concerning.

The maintenance data also substantially expanded the long-term safety database. How would you characterize the safety profile of obefazimod at this stage of development, and what gives you confidence in its benefit-risk profile?

I think the safety looks quite good. When the induction data was first released publicly, there were a few malignancies in the 50 mg dose, and I think that was a little bit misinterpreted. When interpreting rare safety events like malignancy, it's important not to focus solely on raw numbers. These events were uncommon, and simple case counts can be misleading, particularly when treatment exposure differs across groups.

With maintenance, we have more exposure, and that gives us a better picture of safety. The 50 mg group had the greatest cumulative treatment exposure and included many of the most treatment-refractory patients. When patients receive a treatment for longer, we'd naturally expect more events in that group. So the important thing is to look at exposure-adjusted incidence rates rather than raw counts.

Across both the phase 2 and phase 3 programs, there's over 1,700 patient-years of exposure. Rates of things like non-melanoma skin cancer are consistent with published malignancy rates in ulcerative colitis. There was a prostate cancer and a breast cancer in the 50 mg dose, but those aren't rare cancers, and they occurred in patients where we'd expect them. The available data doesn't suggest a dose-dependent malignancy signal with obefazimod. We have phase 2 data going out beyond four years now, and when you weigh the benefit against what we're seeing for safety, it's a very favorable benefit-risk profile.

Ulcerative colitis has become an increasingly crowded treatment landscape with numerous advanced therapies available. Based on the totality of the ABTECT data, where do you envision obefazimod fitting into clinical practice if it's approved?

You're absolutely right that it's becoming a crowded landscape. Whenever a new molecule comes into the clinic, we need to ask what it really brings to the table compared to what we already have. Here, we have a once-daily oral small molecule with a different mechanism of action than anything currently available in the clinic. That mechanism is intriguing to us because it increases expression of miR-124, a naturally occurring microRNA, which brings the immune system back into balance rather than acting as a true immunosuppressant like some of the therapies we currently have.

Editors' note: Panaccione has relevant disclosures with Abbott, AbbVie, Abivax, Alimentiv, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Ferring, Galapagos, Gilead Sciences, Janssen, Merck, Novartis, Pfizer, Takeda, and others.

References

1. Abivax announces landmark Phase 3 ABTECT maintenance trial results evaluating obefazimod in moderately to severely active ulcerative colitis. News release. Abivax. June 1, 2026. Accessed August 19, 2026. https://www.globenewswire.com/news-release/2026/06/01/3304711/0/en/abivax-announces-landmark-phase-3-abtect-maintenance-trial-results-evaluating-obefazimod-in-moderately-to-severely-active-ulcerative-colitis.html

2. Abivax reports positive ABTECT maintenance Part 2 results for obefazimod, demonstrating meaningful clinical benefit in refractory ulcerative colitis patients and strengthening the Phase 3 maintenance safety database. News release. Abivax. June 29, 2026. Accessed August 19, 2026. https://ir.abivax.com/news-releases/news-release-details/abivax-reports-positive-abtect-maintenance-part-2-results/