A Food-Allergy Fix Hiding in Plain Sight

Tami McGraw used to be so allergic to red meat that even fumes from cooking might send her into anaphylactic shock. She couldn’t fry sausages for her family. She couldn’t go to cookouts with friends. Once, she passed out driving home with her son after accidentally inhaling fumes while volunteering at the school cafeteria. “That’s the closest I came to dying,” she told me. Every whiff of sizzling meat, every journey out of the house came spring-loaded with danger.

The episode in the school cafeteria rattled McGraw so much that she brought up with her allergist a then-unorthodox therapy called Xolair. Xolair is a bimonthly or monthly injection originally approved in 2003 for asthma, which McGraw has been diagnosed with. But doctors had long suspected that Xolair could do more, and they had already started noticing an intriguing curious side effect in asthma patients: Their allergic reactions to food were diminished too.

McGraw’s doctor agreed to prescribe her Xolair—officially for asthma but unofficially with the hope of treating her allergy. Soon, she found she could cook red meat in the house again. Then, she could eat it. She had a bite of bacon, a bite of hamburger. All good. McGraw still doesn’t care for red meat—doctors recommend continuing avoidance, and she had developed a distaste after her allergic reactions anyway—but she no longer worries about a cross-contaminated utensil or fumes lingering in the air. “I could go in places without fear,” she said. “I could go out to eat.” Since 2016, she has been living, in other words, a pretty normal life.

Earlier this year—more than 20 years after Xolair first came to market and eight years after it transformed McGraw’s life—Xolair was approved for food allergies. The drug is finally available to the millions of Americans with severe, sometimes-fatal allergic reactions. Rates of food allergies have been rising this entire time, nearly doubling in children since Xolair was initially developed. Though it is not meant to be a cure, the drug provides enough protection against accidental exposure to bring tremendous relief.

“It’s a complete life-changer,” says Robert Wood, a pediatric allergist at Johns Hopkins who co-led the study that recently got Xolair green-lighted for food allergies. And it’s been a long time coming.

Xolair works by intercepting immune molecules called IgE, known to be a trigger in allergic reactions. For this reason, its potential to calm food allergies was apparent from the very beginning, but a frustrating series of events in the 2000s kept drugs like it out of many patients’ reach.

First, a similar drug that was ahead of Xolair in development was unceremoniously shelved in 2004—despite promising results in treating peanut allergy—as the result of a bitter legal battle between its manufacturer and Xolair’s. This cleared the path for Xolair, which suffered a different setback: Its clinical trial for peanut allergy was terminated early in 2006 for safety reasons unrelated to the drug itself. Two children had severe reactions when they were being “challenged” with peanuts to gauge the extent of their allergy. Xolair’s manufacturer deemed the peanut challenges, and therefore the whole trial, too risky. The incomplete results from the study, when they were published, nevertheless looked encouraging.

Throughout this period, Xolair was available to patients with asthma, and in 2014, it was also approved for idiopathic, or unexplained, chronic hives. Both of these conditions tend to involve high levels of IgE, the molecule that Xolair blocks. They often overlap with food allergies, says Scott Commins, an allergist at the University of North Carolina, who is also McGraw’s doctor. This led to a two-tier system: Commins could offer Xolair to food-allergy patients who, like McGraw, also had asthma or chronic hives. Patients who didn’t have multiple conditions were out of luck. They could get Xolair off-label, but few could afford it. Insurance companies do not cover off-label prescriptions, and the list price runs $30,000 to $60,000 a year. “We were definitely not able to use it as much as we wanted,” Commins told me.

To secure FDA approval and insurance coverage of Xolair for food allergies, patients needed more than promising preliminary data and anecdotal stories: They needed a big, definitive clinical trial. In 2019, Wood and other researchers finally secured the funding for such a trial, dubbed OUtMATCH, which was a collaboration between the National Institute of Allergy and Infectious Diseases and Xolair’s manufacturers. The results of the first of its three stages were published this February: After 16 weeks on Xolair, two-thirds of participants allergic to peanuts and at least two other foods (such as milk and eggs) were able to eat the equivalent of two and a half peanuts. A similar proportion could eat their other allergy foods too. This study persuaded the FDA to approve the drug for food allergies.  

Xolair is most life-changing for patients with allergies that are difficult to avoid—either because their allergen is rarely labeled or because they react to even trace amounts, or both. That includes people like McGraw, and it includes people like Christine Robinson, whom I interviewed five years ago about her corn allergy. Chemicals derived from corn, it turns out, are hidden just about everywhere in processed food: Robinson would react to bottled water, iced tea, table salt, bagged salads, frozen fish, the wax on apples and oranges. She went out with an armament of Benadryl, Zantac, prednisone, and EpiPens, the last of which delivers a jolt of emergency epinephrine to counteract anaphylaxis. Since we first talked, she has also started Xolair. “It’s amazing, really,” she told me recently. She still doesn’t eat corn, but her reactivity is much lower. “The reactions are not an emergency now, they are an annoyance.” Recently, her EpiPen expired before she had occasion to use it.

Patients with only mild allergies, on the other hand, might not find an injection every two or four weeks worth the trouble. And Xolair did not work as well for one-third of people in the trial. Predicting who will or will not respond to Xolair and understanding why is one of the big remaining questions ahead, says Scott Sicherer, an allergist at Mount Sinai and a principal investigator on the OUtMATCH trial.

Xolair also has the practical advantage of treating multiple food allergies at once, says Stacie Jones, a pediatric allergist at Arkansas Children’s Hospital who is also part of the OUtMATCH study. The only other treatment available, oral immunotherapy, is food specific: Patients ingest a tiny daily amount of their allergy food, gradually upping the dose over time until they reach a maintenance dose. An oral immunotherapy for peanuts called Palforzia is approved, and some allergy doctors now offer custom regimens for a number of foods. But the process can be arduous, and patients with multiple allergies generally need to go through it for each food.

Xolair and oral immunotherapy potentially could be used together. The second of the three stages of the OUtMATCH trial was designed to investigate whether adding Xolair can make oral immunotherapy safer and more effective. The third stage follows participants after they discontinue Xolair, and as some reincorporate allergy foods back into their diet. “What we’re learning in the clinic and in the study is that most people can actually start to eat the food they’re allergic to,” Wood told me, adding that the results would be published in the coming months. The data, if convincing, could dramatically change how Xolair is used—the drug is currently approved only alongside strict avoidance.

In our conversation, Wood also evinced more than a hint of impatience about the two decades needed to make Xolair available for food allergies in the first place. “It’s honestly quite ridiculous that it took this long,” he told me. “But at least we’re here now.”