SILVER SPRING, Md. -- An FDA advisory committee voted 7-2 on Friday to approve a standardized peanut protein powder developed by the biopharma company Aimmune Therapeutics as sufficiently efficacious to prescribe for life-threatening peanut allergies in patients ages 4 to 17.
Members of the Allergenic Products Advisory Committee also voted 8-1 that the new treatment, known as AR101 and to be marketed as Palforzia, is safe. The FDA usually follows its committees' lead and is expected to make its final decision early next year.
Oral immunotherapy (OIT) has been receiving more attention as a possible way to benefit the millions of people who suffer with food allergies. Roughly 2% of the non-adult population cannot tolerate peanuts, according to recent studies that found they can cause asthma as well as systemic reactions including fatal anaphylactic shock. Advocates believe OIT can curb the anxiety and fear of inadvertent exposures, in addition to the adverse physical effects.
But OIT has its skeptics, too, who worry the long-term effectiveness and tolerability of the first protective therapy for peanut allergy in what Aimmune hopes will be part of a family of products with blockbuster commercial potential. Experts say avoidance is now the only sure solution but agree this is easier said than done. Severe reaction can be triggered by microscopic amounts of peanut, which can appear in a wide range of foods and is not always listed on package labels.
Clinical studies of Palforzia demonstrated that it desensitizes most affected adults and children, but the optimal treatment duration and dose are not yet known. Slowly increasing daily exposure to small amounts of peanut powder – from less than 1 mg to as much as 600 mg per day -- over several months allowed study participants to build up tolerance and reduce the incidence and severity of reactions in many patients who maintained smaller doses for up to 3 years.
The problem is that other studies have indicated that benefit for most peanut-allergic individuals disappears after stopping or lowering the dose of OIT. Thus, adherence to therapy appears to be an indefinite necessity.
A double-blind study published online last week in The Lancet found that blood tests administered before OIT could predict the success of therapy. The phase II study -- supported by the National Institute of Allergy and Infectious Diseases (NIAID) -- may inform who may benefit from peanut OIT and what changes in this experimental treatment should be implemented.
That study also found that eliminating or reducing the daily maintenance dose diminished patients' ability to tolerate peanuts after 1 year.
As a safety precaution, the committee voted 8-1 to recommend a Risk Evaluation and Mitigation Strategy as a condition of approval. Physicians who prescribe the drug would have to certify that patients and/or their caregivers have confirmed they will always carry an epinephrine auto-injector such as an EpiPen to treat severe allergic reactions.
"I voted 'yes' because I thought the data was quite clear, and I would actually compliment the sponsor on the extent and caliber of the studies," said panel member Ira Finegold, MD, a professor of medicine at Icahn School of Medicine at Mount Sinai in New York.
Other panel members disagreed. Said John Kelso, MD, an allergy specialist at the Scripps Clinic in San Diego: "People on the drug are twice as likely to have a reaction that will require epinephrine." Erica Brittain, PhD, an NIAID statistician, concurred. "It is hard to argue that a product that increases the risk of adverse events is safe," she said.
Pamela A. Guerrerio, MD, PhD, chief of NIAID's Food Allergy Research Unit, urged patients to take the same dose of the medication at the same time each day after a meal or snack and avoid hot water and physical activity for 1-2 hours after dosing to prevent adverse reactions.
Besides its allergic potential, the drug is not always well-tolerated. In OIT trials, about 10%-30% of participants drop because of the gastrointestinal side effects.
Mark Dykewicz, MD, an allergist-immunologist in St. Louis, insisted that transparency about the downsides is essential. "A complete understanding of the risks should be part of the [risk evaluation and mitigation] approach," he said. "I want to ensure that parents are fully informed."
Said Finegold, "It is clear that this therapy can hurt some patients and ... they need to know the possible consequences in advance," and FDA officials agreed.
"The agency felt a black box warning on the label was important and if the committee feels additional safeguards should be discussed, we would like comments and suggestions on that," said Marion F. Gruber, PhD, of the Center for Biologics Evaluation and Research, which is reviewing the Palforzia application.
Sofella A. Maleki, a research scientist at the U.S. Department of Agriculture who focuses on making peanut products less allergenic, praised consumer advocates for their persistent lobbying. "The community came together and urged controlled doses and I think this is how approval came about," she said before a large and enthusiastic crowd of patients and caregivers that gave emotional testimony about dramatic improvements in a child's health once the drug regimen began.
The panel agreed that despite its flaws, OIT therapy is an important option for coping with peanut allergies 24/7. "Even though it is not perfect and not for everyone, Palforzia goes a long way to help patients and improves their quality of life," Finegold concluded.
Gruber, however, qualified the benefits of Palforzia outweighing its risks with a caveat. "If the FDA finds it necessary to mitigate use of the drug," she warned, "the company will be required to take reasonable steps -- if there are violations, approval could be suspended."