Up-and-Coming Treatments for Ulcerative Colitis Have Novel Mechanisms of Action

Cobitolimod from InDex, a Swedish company, and obefazimod, from Abivax, a French company, could be first-in-class medications for ulcerative colitis.

Current treatment for ulcerative colitis aims to induce remission in those with active colitis and maintain remission once it is achieved. The development of new biologics and Janus kinase (JAK) inhibitors has made this goal possible for some people living with ulcerative colitis. However, a large proportion of patients may fall through the cracks. According to the Crohn’s and Colitis Foundation of America, roughly half of the people with ulcerative colitis are in remission in a given year.

Although currently available treatments provide a range of therapeutic options for ulcerative colitis, a number of patients cannot tolerate or do not respond to these therapies. In some cases, patients simply stop responding to treatments. For this population, agents with alternative mechanisms of action may be beneficial.

The late-stage pipeline for ulcerative colitis includes at least two candidates with novel mechanisms of action that may help fill this gap.

Cobitolimod, developed by Swedish company InDex Pharmaceuticals, is a potential first-in-class agent for the treatment of moderate-to-severe left-sided ulcerative colitis in patients who do not respond to conventional, biologic, or JAK inhibitor treatments. Cobitolimod activates Toll-like receptor 9 (TLR9), which reduces inflammation and promotes colon healing. In a phase 2 study, cobitolimod was better than placebo at inducing remission at 6 weeks. The candidate is currently in the phase 3 CONCLUDE trial with an estimated completion date of December 2024.

Abivax, headquartered in Paris, is also moving a potential first-in-class treatment through the pipeline. Obefazimod is a micro-RNA-124 (miR-124) upregulator that blocks the production of pro-inflammatory modulators involved in ulcerative colitis. In a phase 2 study, obefazimod met all primary and secondary endpoints and was effective in participants who had not responded to biologics or JAK inhibitors. The drug is currently in the ABTEC phase 3 trial evaluating its use in patients with moderate-to-severe ulcerative colitis who have not responded to conventional, biologic, or JAK inhibitor treatments. Preliminary results are expected in May 2024.