The study that led the FDA to approve Xolair as the first treatment of multiple food allergies was unveiled February 25 to a packed convention room at the AAAAI allergists’ meeting.
The Phase 3 OUtMATCH study, now published in the New England Journal of Medicine, contains compelling findings on omalizumab (or Xolair). The injectable biologic drug was tested in patients with allergies to peanut and at least two of six other foods.
“This is the first medicine to reduce the risk of reactions to multiple foods and I believe it essentially works equally for all [allergenic] foods,” said Dr. Robert Wood, the co-lead investigator of OUtMATCH.
The clinical trial involved 177 children between 1 and 17 years old, with 118 put on active treatment for 16 to 20 weeks. The rest received placebo injections. (Neither group knew which study arm they were in.) Study participants had confirmed allergies to peanut and at least two other foods among milk, egg, wheat, cashew, hazelnut and walnut.
Wood told the allergists that, in food challenges, 67% of patients getting Xolair shots achieved a primary study endpoint. They could tolerate at least 600 milligrams (mg) of peanut protein – about 2½ peanuts – without significant symptoms. By comparison, only 7 percent of patients on placebo shots could manage that.
Xolair raised the threshold of patients’ tolerance for other allergens, too. Similar percentages of participants could tolerate 1,000 mg of five of the six other allergens without major reactions. (That equaled about 2 tablespoons of milk or a quarter of an egg.)
This wasn’t the end of the story. Wood noted with Xolair therapy, “more than 50% could eat the equivalent of 16 peanuts” without reacting.
Tolerating Large Allergen Amounts
“I have seen how debilitating food allergies can be for patients and their loved ones, as they are consumed by the fear of accidental exposure,” says Wood, the director of pediatric allergy and immunology at Johns Hopkins Medicine in Baltimore.
The OUtMATCH results show a reassuring level of protection in case of such exposures. The FDA has approved Xolair on that reaction protection basis. Patients will be advised to continue avoiding their food allergens and carrying epinephrine.
Following the treatment period, study participants underwent food challenges. These are done over many hours – and the total consumed is called the cumulative dose. With peanut, those who reached the primary endpoint of 600 mg, actually ate a cumulative 1,044 mg of peanut.
That’s equal to 4 peanuts, and 44 percent could safely consume a remarkable 6,044 mg – about 25 peanuts. The average was 16 peanuts.
As well, 80% on the treatment safely consumed a cumulative dose of 1,044 mg of any of the individual allergens, while 69% attained the same with two foods.
“Many patients can actually eat larger amounts of the food they’re allergic to,” Wood told Allergic Living. “But the initial approach will be very much following the FDA package label” for protection from accidental exposures.
Xolair: An Option for Toddlers
Dr. Brian Vickery, another author of the study, calls Xolair’s approval for food allergy “a major milestone for patients.”
However, Vickery, the chief of the allergy and immunology department at Emory University, underscores that the therapy is not a cure, and won’t be for everyone. “It will be available only to certain patients based on their clinical history, weight, and IgE level.”
Based on such factors, patients in the study had a range of omalizumab doses, though most participants were on a regimen of 300 mg every two weeks.
Xolair has been approved for over two decades in severe asthma, as well as other allergy-related conditions. But the FDA’s recent approval for food allergy approval marks the first time this biologic will be available to very young children. “We were really excited to get approved down to age 1,” says Wood.
Vickery explains that the FDA in fact required the research team to ensure plenty of toddlers were enrolled to test for safety and effectiveness. Sixty-eight kids under the age of 6 took part. He found that important, as “this is the age when most food allergies come to clinical attention.”
Even though Xolair treatment requires injections, Vickery says compliance in the study with young kids was strong. Distraction techniques and topical anesthetic made the shots more palatable.
College Kids and Xolair Shots
Wood was also pleased that the FDA approved the treatment for adults (up to age 55). He singles out college students “as another at-risk population where we think the drug is going to be especially popular and useful.”
But some parents have raised the issue: Will a teenager comply with injections on a regular basis? Dr. Sharon Chinthrajah, the co-lead on the study, acknowledges that “shots are not easy – whether in a 2-year-old, a 17-year-old or a 33-year-old.” But the director of the research unit at Stanford University’s allergy center says, “this is where it is amazing to have choices to offer our patients.” After consultation, “it’s up to them to decide, and sometimes for parents to nudge.”
With oral immunotherapy for food allergy desensitization, patients do need to be mindful about reaction risk factors like exercise or hot showers after dosing. Chinthrajah says a benefit for those of college age is that these are not risk factors for Xolair.
Yet, the biologic does carry a warning for possible anaphylaxis to the medicine itself. (Wood characterizes that risk as very small.)
Who Wasn’t a Responder?
Xolair is called an “anti-IgE” biologic, since it can reduce reactions by neutralizing the IgE antibodies that set off allergic symptoms. However, the study, funded largely by the National Institute of Allergy and Infectious Diseases (NIAID), showed the effects can vary.
In OUtMATCH, 33 percent of children didn’t achieve the researchers’ endpoint criteria to qualify as a “responder”. Even so, Wood notes that many of them substantially increased the amount of allergens they could consume. For example, a child who went from reacting to 3 mg of peanut to 300 mg (about one peanut) would still have significantly more protection than before.
However Wood told the meeting that there were “some treatment failures.”
“In this study, we had 14% who couldn’t get to 30 mg of any food [allergen].” The study co-lead said physicians and families “need to be aware of this difference in individual patients.”
He notes that this is why the comfort level for Xolair for food allergies is as a safety net against allergen accidents. Yet, the investigator did tell his assembled colleagues that “a dream for the future is that maybe some of the biologics could be disease modifying.” Considerably more study would be required to achieve that goal.
Also underway is stage 2 of the OUtMATCH study, in which Xolair is being used alongside multi-allergen oral immunotherapy. Wood expects the research for that stage to be complete by August 2024.
With files from Jenifer Goodwin
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FDA Approves Xolair to Avert Severe Food Allergy Reactions
Is Your Allergic Teen Taking Food Allergy Risks?
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