Ligelizumab

Peanut bans at schools. EpiPen training at summer camps. Parents struggling to find an alternative to PB&J. The massive rise in food allergies transformed how many American children grow up. But a combination of better biological understanding, and a new use of an old drug, has opened up a potentially huge market in biopharma — and effective treatments for patients. It’s turned Xolair, a 23-year-old asthma medicine, into a blockbuster after it won expanded approval in 2024 to treat food allergies. Since then, sales of Xolair have jumped from under $2 billion annually to more than $4 billion. Cash has started flooding into startups, with Merida Biosciences , Excellergy and Poplar Therapeutics all emerging from stealth over the last 12 months, raising a combined $241 million in their respective Series A rounds. And big pharma is ready to engage, too. Already this year, GSK acquired RAPT Therapeutics for $1.9 billion upfront to get its allergy drug ozureprubart; Novartis, seeking to bridge the incoming Xolair cliff, bought out six-month-old Excellergy last week for up to $2 billion; and Regeneron has added allergic programs for food, cats and birch tree pollen as well. The resurgence suggests a clear and eager demand among patients and families for new treatments. If other companies can develop better and longer-lasting allergy drugs, profits should follow and patients should benefit. “Before there was more of a notion that you could avoid certain foods,” said Angelika Jahreis, Novartis’ global head of immunology development. “But now we understand how serious the consequences can be, how cumbersome it is, and how many patients have multi-allergy, allergic diseases, and that they cannot just avoid allergens.” In 2024, the CDC estimated about 18 million adults and four million children reported an allergy to at least one food. The burgeoning competition comes with an unusual circumstance: The first Xolair biosimilar hit the market last year, and more are expected to launch in 2026. Should the newer treatments work, they’d be competing against cheap generics rather than other prescription drugs. Next comes the hard part: The companies’ drugs need to succeed in clinical trials. Such an emphatic sales uptick since 2024 begs an important question: Why did Novartis and Genentech, the Roche subsidiary that originally co-developed Xolair, wait so long to seek approval in food allergy? The 20-year gap between Xolair’s approvals can be attributed first and most significantly to the FDA’s reluctance to expose children to severe allergic reactions, said Robert Wood, a professor of pediatric allergy and immunology at Johns Hopkins. In the early 2000s, such studies often involved exposing kids to peanuts to see how much allergen they could tolerate before having a serious reaction, a “challenge study” similar to how some vaccines are developed. “The FDA, at that point, made clear to them that a food challenge outcome would not ever get them an approval,” Wood said. It was too risky. That same year, Genentech canceled a food allergy study after two children in the trial apparently suffered severe responses while taking allergy tests, according to a Wall Street Journal report from the time. With the FDA’s position and the trial’s issues, the company’s leadership got “really cold feet,” Wood said. “They literally just lost interest in bringing [Xolair] forward for food allergy.” The tide started to turn in 2012, when Wood and his Johns Hopkins colleagues won an NIH grant to test Xolair in a challenge study for food allergy. The trial showed patients could tolerate significantly more exposure to peanuts after taking Xolair for six months. That NIH trial alleviated some of the FDA’s concerns over food challenge studies. Regulators then opened the door to approvals when, in 2020, a California biotech called Aimmune Therapeutics won FDA approval for its treatment Palforzia — described as a daily, oral immunotherapy to treat severe peanut allergies. “If you’re doing a study in cholesterol lowering, there’s a clear endpoint, right? For food allergy, there was no endpoint,” said Mike Dybbs, a partner at Samsara BioCapital, which invested in Excellergy. “I give Aimmune a lot of credit for working with the FDA to create a registration path.” Each dose of Palforzia contained 600 mg of peanut protein (equivalent to about two peanuts) and patients in the study had a 67% chance of avoiding a severe reaction. The company was quickly snapped up by Nestlé for $2.6 billion. This, plus Wood’s research, helped set the stage not only for Xolair’s food allergy approval but also for other companies looking to develop competitors. While companies were working through the regulatory issues, researchers were getting a much better understanding of the biology behind Xolair and allergies more broadly. Most food allergies occur when the body’s immune system mistakenly identifies an allergen as a foreign invader and activates an antibody called immunoglobulin E, or IgE, to attack it. IgE once played a pivotal role in humans’ defense against parasites, but now that most parasites are uncommon in the developed world, this activation can lead the immune system to overreact to everyday foods and airborne allergens. Originally approved for patients with allergic asthma, Xolair targets and binds to the free-flowing IgE circulating in the bloodstream, which causes the condition’s hallmark inflammation. Researchers and clinicians also realized Xolair’s cancer risk — its label included a warning for an increase in primary malignancies — was not as serious as originally thought. The biotechs that have emerged to create Xolair successors are also trying to leverage this biology. But they’re doing so with a range of approaches. Merida, which put together the biggest raise at $121 million in April 2025, wants its treatment to not only bind to free-flowing IgE, as Xolair does, but to degrade it quickly, producing a faster response, chief scientific officer Dario Gutierrez told Endpoints. “The half-life of IgE, naturally in patients, is a couple days. Xolair increases the half-life to [about] 20 days,” Gutierrez said. Merida, on the other hand, “is specifically trying to attach itself to the free-flowing IgE and then destroy it before it can be recycled.” Excellergy wants its drugs to also separate the IgE that’s already attached itself to certain white blood cells, theoretically making it more effective. Previously, this was considered undruggable and Excellergy only recently dosed its first human patients. Poplar’s treatment, meanwhile, is described as an IgE “depleter,” which uses an undisclosed “triple-action mechanism” to hit free-flowing IgE, prevent it from binding to white blood cells, and reduce its production. Phase 1 data are expected in the second half of this year. Regeneron’s food allergy program is lagging behind its cat and birch allergy drugs, but it’s shooting for a combination approach with the megablockbuster Dupixent, which targets a different mechanism than IgE in a wide variety of conditions. Companies also see an opportunity for drugs more similar to Xolair that can be dosed less frequently. That’s the thesis behind GSK’s acquisition of RAPT, whose program ozureprubart is currently in a Phase 2b study. If everything works out, data could come next year with a possible launch in 2031. “The thing we liked about a Xolair-like product and a longer-acting version is the absolute convenience it provides,” GSK’s global business development chief Chris Sheldon said. Despite the excitement, there is no guarantee any of these approaches will succeed. Preventatively treating food allergy has remained a challenge among the few companies that have attempted it. Alladapt Immunotherapeutics shut down in 2024 after it couldn’t find the cash to run a Phase 3 study for an experimental food allergy drug, despite its earlier success. In January 2024, Novartis terminated a Phase 3 ligelizumab trial in peanut allergy because of dosing challenges, and the drug no longer appears on the company’s pipeline webpage. And Palforzia will soon be coming off the market for reasons unrelated to its safety or effectiveness. But the toughest hurdle could be the entrance of Xolair biosimilars, with one already approved and more expected this year. Xolair’s current annual list price is as high as $60,000 , and generics will likely be cheaper. A true Xolair competitor probably won’t reach the market until RAPT’s predicted 2031 launch. The Merida, Excellergy, Poplar and Regeneron food allergy drugs don’t yet have launch timelines. And due to the unusual timing of the biosimilar competition, the newer drugs will need to show substantial improvements in both convenience and effectiveness over Xolair to be widely used, said Heath Lukatch, co-founder of Red Tree Venture Capital, which seeded Excellergy. “In order to compete against those biosimilars with a brand new product, that’s just going to be the ticket to play,” Lukatch said.