New IL-7 Antagonist Lusvertikimab Shows UC Efficacy

BERLIN — Lusvertikimab, a first-in-class interleukin 7 (IL-7) receptor antagonist, demonstrated clinical and endoscopic efficacy in patients with moderate to severe ulcerative colitis (UC) in the 10-week induction period of a randomized, placebo-controlled, phase 2 clinical trial.

Lusvertikimab is unique in targeting the IL-7 receptor, a key player in immune-mediated inflammation.

“We have a new mode of action in ulcerative colitis,” with a strong safety profile, lead investigator, Arnaud Bourreille, MD, associate professor of gastroenterology from Nantes University Hospital, Nantes, France, told Medscape Medical News.

“We achieved the primary endpoint” — improvement in the modified Mayo score (MMS) from baseline to week 10 — “for both the low dose and the high dose of lusvertikimab,” said Bourreille, who presented the findings at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress. “For us practitioners, this is very good news.”

Current treatment options for UC remain limited, especially for patients with an inadequate response to biologics or small molecules.

Overall, biologics are only effective in around half the patients, Bourreille noted. We need other treatments that have different mechanisms of action, as is the case with lusvertikimab.

The multicenter, double-blind CoTikiS study evaluated the IL-7 receptor antagonist in 136 adults with moderately to severely active UC (MMS, 4-9) and inadequate response to conventional therapies and/or failure to advanced therapies. Around 40% of the patients were exposed to one or more biologics.

The 50-week study had a 10-week induction period with two doses of lusvertikimab (450 and 850 mg), followed by a 24-week open-label extension, where patients received infusions of the high dose (850 mg) every 4 weeks, and a 16-week safety follow-up period free of treatment.

For the induction period, patients were randomized 1:1:1 to receive placebo (n = 49), 450 mg lusvertikimab (n = 35), or 850 mg lusvertikimab (n = 50) intravenously at weeks 0, 2, and 6. The diagnosis in two patients was modified to Crohn’s disease; therefore, they were not included.

In meeting the trial’s primary endpoint, lusvertikimab significantly reduced disease severity compared with placebo at week 10 in both dose groups separately and when pooled.

The MMS in the 450-mg group showed a difference of −1.16 points vs placebo (P = .019), whereas in the 850-mg group, the MMS showed a difference of −0.9 points vs placebo (P = .036). In the pooled group, the difference was −1.00 points vs placebo (P = .010).

The secondary endpoints of clinical remission and endoscopic remission also favored lusvertikimab for the pooled doses vs placebo, at 16% vs 4% (odds ratio [OR], 4.25; P = .066) and 25% vs 13% (OR, 2.33; P = .120), respectively.

For the other secondary endpoints, 32% achieved endoscopic improvement in the pooled group vs 13% in the placebo group (OR, 3.29; P = .027), and the mean score change in the UC Endoscopic Index of Severity was −1.35 for the pooled group vs −0.32 for the placebo group (P = .007).

Fecal calprotectin was reduced by 830 μg/g in the 450-mg group (P =.009), by 635 μg/g in the 850-mg group (P = .018), and 716 μg/g in the pooled group. It was increased by 189 μg/g in the placebo group (P = .004).

No safety concerns were reported.

Bourreille noted that there was a little more lymphopenia in patients on lusvertikimab vs placebo, which is explained by the drug’s mechanism of action. However, “it was transient lymphopenia, without any infection and without any need to interrupt the treatment.”

Next, Bourreille said, we need to demonstrate the efficacy and the safety of the drug in the long term.

“There may be a place for lusvertikimab in patients with Crohn’s disease because the mechanism of action of IL-7 receptor antagonist would potentially have good efficacy in that disease too,” he added.

Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, who co-moderated the session, pointed out that the results supported further clinical development of lusvertikimab.

“As elevated mucosal IL-7/IL-7R expression predicts refractoriness to currently used biologic therapies, it would be very interesting to see the potential of lusvertikimab as a treatment for patients who were exposed to advanced therapy or as part of combination therapeutics,” he said.

The study was funded by OSE Immunotherapeutics. Bourreille received funding from OSE Immunotherapeutics; grants from Takeda and Mauna Kea Technologies; and personal fees from AbbVie, Celltrion, Ferring, Galapagos, Gilead, MSD, Medtronic, OSE Immunotherapeutics, Janssen, Pfizer, Roche, Takeda, Tillotts, and Vifor Pharma. Bamias reported receiving grants from Takeda, AbbVie, Mylan/Viatris/Biocon, Genesis Pharma, Ferring, Vianex, and Aenorasis and personal fees/honoraria as advisor/lecturer from AbbVie, Adacyte Therapeutics, Amgen, Bristol Myers Squibb, Ferring, Galenica, Genesis Pharma, J&J, Eli Lilly, MSD, Mylan/Viatris/Biocon, Pfizer, Takeda, and Vianex.