An expert advisory panel has recommended that the Food and Drug Administration approve Aimmune Therapeutics’ oral immunotherapy (OIT) treatment for peanut allergy in children and teens.
The FDA is expected to make its decision on AR101 in January 2020. If the therapy gets the green light, it will become the first approved treatment for a food allergy.
The nine-member panel, which included several allergists, voted 7 to 2 on Sept. 13, 2019 that efficacy results from Aimmune’s clinical trials were sufficient to recommend AR101’s approval.
They then voted 8 to 1 that the safety data were sufficient as well, provided the protocol includes a risk management plan for families and physicians. It would require epinephrine to be carried and that the first two treatment doses are administered at a certified facility equipped to treat anaphylaxis.
“I voted ‘yes’ because I thought the data was quite clear,” said panel member Dr. Ira Finegold, a professor of medicine at the Icahn School of Medicine at Mount Sinai in New York.
Fellow panelist Dr. Soheila Maleki, a peanut allergy researcher with the U.S. Department of Agriculture, found the efficacy data “impressive,” and earlier said AR101, recently given the brand name Palforzia, could provide needed standardization in oral immunotherapy.
Palforzia capsules contain peanut powder with a consistent, calibrated level of allergenic proteins. The amount of protein powder in a capsule starts out minuscule, and gradually increases until the patient reaches a daily maintenance dose amount of 300 milligrams, or roughly one peanut.
The therapy is meant to desensitize, so a peanut-allergic child will no longer react to small amounts of the legume. But it is not a cure. The panel discussed that, if approved, patients and caregivers will need to be counseled against freely eating peanut products once on a maintenance dose.
Families on the Anxiety Life
Despite the two highly favorable votes, the hearing results were no slam dunk. The day-long hearing featured intense discussion, with panel members grilling Aimmune executives and researchers on specifics of their study data. They were particularly concerned about allergic reactions, which occurred mostly during updosing to reach maintenance.
A public commenting period also brought drama – as families related emotional stories of children’s experiences with anaphylaxis, exclusion and life-threatening reaction fears.
“As a food allergy parent, you never stop worrying, you worry about every little cough, you worry about when your child will start dating and [whether] his teacher keep him safe,” said Amy Applegate of Indiana, whose son successfully completed Aimmune’s Palisade trial. “Today our anxiety has lifted,” she said, holding back tears.
Cathy Heald of Dallas spoke of the constant fear of food mistakes. Her son Charlie took part in the clinical trial and, in an oral challenge, was able to eat a dozen peanuts. Now 12, the boy has even flown to Europe without his parents. “The peace mind is invaluable,” said Heald. (Aimmune paid for travel to the hearing for the Applegates and Healds.)
“My life was like navigating a minefield,” Californian Tessa Grosso, 16, told the panel. As an exquisitely allergic child with multiple allergies, she underwent OIT treatment at Stanford University. Today, she has “the ability to live without fear of food,” something she stressed every child deserves.
Community advocates – from FARE to the Asthma and Allergy Foundation of America (AAFA), Allergic Living and the Allergy and Asthma Network (AAN) – gave voice to reasons why the food allergy community urgently needs therapies.
“Avoidance alone is not enough,” said Charmayne Anderson, director of advocacy for AAN.
Risks vs. Benefits
Safety was the biggest consideration for the advisory panel, since any food allergy treatment carries the risk of severe anaphylaxis. The experts gave close scrutiny to Aimmune’s data, which showed that 9% of children on AR101 treatment had systemic reactions, more than twice the rate of those taking the placebo.
This also led to an increase in epinephrine use (10% in the treatment group compared to 5% in the placebo group). As well 11% of the kids dropped out of the study because of allergic reactions.
Since the children on placebo didn’t consume peanut, it might seem obvious that fewer of them would have allergic reactions. (The ones they had were accidental exposures.) However, the panel had to weigh the tradeoffs between reaction risks and patient benefits – and whether Palforzia presented an improvement to the status quo strategy of peanut avoidance.
Aimmune’s chief medical officer, Dr. Daniel Adelman, added some assurance, explaining that most reactions were mild or moderate, with predominantly gastrointestinal symptoms.
“Severe events occurred in 10 patients out of more than 1,000 patients exposed,” he said. “Importantly, the incidence of adverse reactions declined from updosing to maintenance, and continued to decrease with prolonged dosing.”
One panel member remained unconvinced. Dr. John Kelso, an allergist at the Scripps Clinic in San Diego, voted ‘no’ on both safety and efficacy, strongly preferring avoidance and education as the approach for peanut allergy management.
Why Approval Matters
Panel member Dr. Gailen Marshall, director of the University of Mississippi’s allergy and immunology division, found Palforzia met the standard for his “yes” votes. Then he added:
“We’ve heard enough desperation in the voices of some of the commenters that if they found a doctor in the community who was not particularly well-trained but who made it [OIT] available versus somebody else who was better trained but chose not to make it available, then they would go for the first option. So I think we need to show leadership in providing the help and support that’s necessary.”
A few panelists made clear that private practice OIT, which is growing across the United States, was not considered an alternative for FDA approval, due to a lack of quality studies, standardized desensitization products or methods. (While practices can offer desensitization without regulatory approval, insurers will not always cover unregulated treatments.)
Dr. Robert Wood, director of pediatric allergy and immunology at Johns Hopkins University School of Medicine, said he would not recommend the Palforzia protocol to his patients because of reaction risks. A critic of OIT for peanut allergy, Wood prefers peanut avoidance and caregiver/patient education for management. Yet, even he backed approval for the Aimmune approach.
“I’ve probably been the most outspoken opponent of OIT being practiced by practitioners with product purchased in the grocery store. This really calls for the need for a well-standardized product, which AR101 is,” said Wood.
The panel had many questions for Aimmune presenters, and wanted more long-term data assessing risks and quality of life improvements. In one risk example, Dr. Stephen Dilly, Aimmune’s former CEO and special advisor, noted that co-factors including exercise, illness and hot showers, had been found to play a role in eliciting a reaction during treatment. Issues like these would be communicated in a risk management plan.
As for long-term results, Dilly says Aimmune has begun conducting a long-term observational study. “Oral immunotherapy is already a reality,” said Dilly. “And what we’re trying to do is to bring it under control, under regulation so that we actually get this data.”
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