A San Francisco-based biotech company is developing a new blocker of the IgE allergy antibody for treating food allergies. Rapt Therapeutics says that, if it proves successful, this therapy will only require an injectable dose every two or three months.
A Phase 1 trial in healthy volunteers indicated that Rapt’s experimental drug, RPT904, was more effective in reducing levels of free IgE antibodies in the blood than omalizumab. Free IgE antibodies circulate in the blood, but aren’t allergen-specific.
Omalizumab (brand name Xolair) is dosed by injection every two or four weeks. It is the first U.S. Food and Drug Administration-approved drug for preventing allergic reactions to accidental exposures in adults and children ages 1 and older with more than one food allergy.
Data from the small Phase 1 RPT904 trial also suggests that free IgE levels remained suppressed for twice as long as with omalizumab.
With RPT904, “there was a deeper and more sustained response,” says Brian Wong, MD, PhD. Wong, who’s an immunologist, is the CEO of Rapt Therapeutics.
Rapt: Extending Therapy’s Potency
The Phase 1 trial of the therapy was conducted by Rapt’s partner in China, Jemincare. About 60 patients received injections of RPT904 at one of five dose strengths, with a few in the trial receiving placebo shots. The doses ranged from 75 to 600 milligrams (mg), which matches Xolair’s dosing range. One group of participants received a 150 mg omalizumab dose for comparison.
At the 150 mg dose, the half-life of RPT904 in the blood was 60 days compared to 26 days for omalizumab. Half-life is how long it takes for the concentration of a drug to decrease by half.
Average free IgE levels also fell further, and remained suppressed for longer, the company reported.
“We project that we can get the same effect as omalizumab, only dosing every two months or three months,” Wong says. “We think this will be much more convenient, and less burdensome. And really importantly, we think that this will increase the adherence and compliance.”
Patients in the Phase 1 trial also tolerated the medication well and there were no severe adverse events.
Targeting Higher IgE and Body Weight
Wong says their modeling also shows that RPT904 could work in patients at higher body weights or high total IgE levels. Although studies are continuing, currently weight and high total IgE levels can be disqualifying factors for omalizumab.
Wong says that high total IgE and higher weight excludes as many as 30 percent of food allergy patients from Xolair treatment. “Our projections suggest RPT904 could address those patients who are not included in the Xolair label.”
Creating a Longer Lasting Therapy
RPT904 is a monoclonal, or lab-made anti-IgE antibody, like omalizumab. As with omalizumab, RPT904 binds to IgE antibodies circulating in the blood. This prevents IgE from binding to receptors on mast cells and basophils, the immune system cells involved in allergic reactions. RPT904 targets the same epitope, or binding site, as omalizumab.
To extend this antibody’s half-life, they made some tweaks. Researchers altered three amino acids, the building blocks of antibodies, that are typically responsible for eliminating the medication from the body.
The alteration enables the antibodies to persist for longer in the body before elimination. “Since it sits around in the body for longer, that means it can do more work,” Wong says.
Next for Rapt Therapy: Phase 2 Trial
Rapt plans to launch a Phase 2b trial of its therapy in the United States by the end of 2025. It aims to enroll 75 patients ages 6 and older with multiple food allergies.
Participants in the double-blind, placebo-controlled trial will be randomized to receive one of three dose strengths of RPT904 or a placebo shot.
Patients will undergo food challenges before starting the trial and again at 20 weeks. Then they’ll have them again, after dosing RPT904 every eight or 12 weeks. Foods will be similar to those included in the OUtMATCH trial for Xolair: peanut, egg, milk, wheat and various tree nuts. They will not include cashew allergy in their Phase 2 study, Wong says.
“Investigators we spoke to said sometimes it takes longer for patients to respond to Xolair for cashew, so for this duration of study they would suggest we leave cashew out,” Wong says. Phase 2 data should be available by the first half of 2027.
In China, Jemincare has ongoing Phase 2 trials for RPT904 for asthma and chronic spontaneous urticaria (hives).
In the U.S., Wong says the company will first focus on food allergy initially because of the “unmet need.”
“It’s so clear there is a need an improved therapy in food allergy. Right now there is only one” for multiple food allergies, he says. “And we think definitely Xolair can be improved upon.”
Investors seem to think so too: the company reported in December 2024 it had raised $150 million in private funding.
Other Therapies in the Works
Another Chinese company, LongBio, is also developing an anti-IgE monoclonal antibody that it too says could extend the time between doses to two to three months. The company announced in November 2024 that it received approval in China to launch a food allergy study there for their drug, LP-003.
Dr. Robert Wood said patients would welcome a medication with a longer dosing interval. But these medications must first show they work as well and are as safe as Xolair, says Wood. He’s co-principal investigator for the Consortium of Food Allergy Research (CoFar), which led the Xolair food allergy trial OUtMatch.
Others have tried. Ligelizumab, another “second generation” IgE-blocker with a stronger affinity to IgE than omalizumab, showed promise in the lab and in early trials. But in January 2024, the company halted its Phase 3 ligelizumab peanut allergy study. At the time, Novartis said it planned to try a different dosing strategy.
“We are very enthusiastic about other treatment options, and very enthused about the studies that will be start. But it’s all wait and see,” Wood says. “We don’t have a perfect drug yet for lots of different factors.”
Related Reading:
After Stopping Xolair, Kids Could Eat Some Allergenic Foods
Palforzia Launches Its Approved Peanut Allergy OIT for Toddlers
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