Oral Biologic Shows Promise for Food Allergy Treatment

PHILADELPHIA — Oral remibrutinib (Rhapsido) increased peanut tolerance in adults with proven allergy to it, with benefits in as little as 1 week, a phase II trial showed.

After 4 weeks on the Bruton’s tyrosine kinase (BTK) inhibitor, 40.0% (n=six of 15) of patients given the lowest 10-mg twice daily dose tolerated at least 600 mg of peanut protein — equivalent to 2.5 peanuts. That proportion rose to half (n=eight of 16) in those on 25 mg twice daily and 86.7% (n=13 of 15) on 100 mg twice daily, whereas none were able to do so on placebo.

All six patients given just 1 week of remibrutinib at 25 mg twice daily after 3 weeks on placebo tolerated the challenge without reaction to at least 600 mg of peanut protein, reported Robert A. Wood, MD, of Johns Hopkins University in Baltimore, at the American Academy of Allergy, Asthma & Immunology annual meeting.

The only treatment approved to treat food allergies without being allergen specific is omalizumab (Xolair), which while “very successful is still not successful for everybody,” noted session co-moderator Yamini Virkud, MD, MPH, of the University of North Carolina at Chapel Hill.

Remibrutinib could be “a game changer” if it provides similar broad efficacy without the regular injections, which even older teenagers can balk at, Virkud told MedPage Today. Beyond the quality-of-life impact, a medication to prevent anaphylactic reactions from accidental exposure would offer ease of use and shelf stability, she added.

Indeed, the efficacy does look similar to what omalizumab showed in the same setting, “and in some ways looked tantalizing, like it could be even better,” commented Wayne G. Shreffler, MD, PhD, director of the Food Allergy Center at Massachusetts General Hospital and Harvard in Boston. In the OUtMATCH trial, 67% of omalizumab-treated multi-food allergic children were able to tolerate 600 mg peanut protein.

And remibrutinib’s rapid mechanism of action would also be a draw in comparison to at least 3 months to get omalizumab to a therapeutic level, Virkud said. Patients and families often seek out treatment around periods when control over the food environment becomes less certain, like a child headed to sleep away camp or to college, or an adult headed to a business trip or abroad for vacation. Needing to start just 1 week before to get a high level of protection “opens up an entire different mechanism of use that I think could help a lot of patients,” she said.

Wood and colleagues’ study included only adults. Younger children, who typically are still in the midst of their vaccine series, could pose a challenge with a drug that inhibits BTK, which “is really important in B cells and probably some other immune cells” that play key roles in immunization, Shreffler said.

“I think the main limitation is going to be how aggressively the FDA will allow, and how well the safety data will support, age de-escalation,” Shreffler told MedPage Today.

The trial included 76 adults (ages 18-55) with a documented history of allergy to peanut, qualifying peanut-specific IgE, and skin prick test for peanut allergen. Baseline reaction-eliciting dose was 30 mg or less on the baseline challenge for all participants. After 4 weeks of screening, they were randomized 2:2:2:1:1 to remibrutinib 10, 25, and 100 mg twice daily for 4 weeks, placebo for 3 weeks followed by 1 week on remibrutinib 25 mg twice daily, or placebo alone. Of the 66 patients who completed the study, 59 made it to the final efficacy analysis without being deemed noncompliant.

The adverse event profile was “very reassuring,” Wood said, without worrisome signals in infections, infestations, nasopharyngitis, upper respiratory tract infection, or potential systemic effects like petechiae, blood cell count dynamics, or new liver enzyme abnormalities.

“Because of these results and other evidence coming in from other disease models, a phase III study in adults and adolescents with IgE-mediated food allergy probably expanding beyond peanuts is planned to start later in 2026,” Wood noted. “My bias looking at the options we have, this is an exciting possibility as we look out in this sort of 3- to 5-year time frame of what we might be able to offer a patient.”