A US Food and Drug Administration (FDA) advisory panel on Friday overwhelmingly recommended peanut (Arachis hypogaea) allergen powder (Palforzia, Aimmune Therapeutics) for children who are allergic to peanuts.
The Allergenic Products Advisory Committee of the FDA's Center for Biologics Evaluation and Research voted in favor of the allergen powder being effective (7 yes, 2 no) and safe (8 yes, 1 no).
The proposed indication is "to reduce the incidence and severity of allergic reactions, including anaphylaxis after accidental exposure to peanut in patients aged 4 through 17 years with a confirmed diagnosis of peanut allergy."
If approved, the peanut allergen powder will be the first-in-class oral immunotherapy treatment for patients with peanut allergy. It will be available as an oral powder that is given once daily by mixing it with food.
"Allergen immunotherapy has come a long way, and I think even though this isn't perfect and it's obviously not for everybody, it will go a long way in helping patients and their quality of life," voting committee member Ira Finegold, MD, chief of allergy, Mt. Sinai St. Lukes–Roosevelt Hospital Center, New York City, said.
Unmet Need
Peanut allergy is a common food allergy that affects approximately 2% of US children. Approximately 80% of children with peanut allergy will remain allergic to peanuts for the rest of their lives.
Peanut allergy requires constant vigilance, and patients and their caregivers have a very real fear of accidental exposure. Avoidance is the only preventive tool for managing peanut allergy. However, many items contain peanuts, and complete avoidance is very difficult.
"When we look at who is having these anaphylactic reactions to peanut, they are disproportionately observed in children, adolescents, and young adults," James Baker, MD, director, Mary H. Weiser Food Allergy Center, Ruth Dow Doan professor of biologic nanotechnology, University of Michigan, Ann Arbor, said in a company presentation to the committee.
Noting that 88% of such anaphylactic reactions occur in patients aged 0 to 18 years, Baker said, "This, therefore, is the target group for prophylactic treatment."
During the open public hearing, numerous patients and their parents talked about the challenges of living with peanut allergy and how this product has changed their lives. Several children said that they feel less socially isolated; children and their parents described no longer having to be as vigilant when touching others, being able to share toys with other children, being able to take public transportation, and being able to eat the same foods as their peers at parties.
Efficacy
The panel's vote follows consideration of efficacy and safety data from seven clinical trials: two phase 2 studies (ARC001 and ARC002) and five phase 3 studies (ARC003, ARC004, ARC007, ARC008, ARC011).
The ARC003 and ARC007 studies were pivotal trials, and the others were uncontrolled. ARC003 provided efficacy data, and ARC003 and ARC007 provided pooled safety data.
ARC003 was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial that included 555 patients aged 4 years to 55 years. Most of the patients (n = 499) were aged 4 through 17 years. To be eligible, participants underwent a double-blind, placebo-controlled food challenge (DBPCFC) before randomization.
Participants were randomly assigned in a 3:1 ratio to receive peanut allergen powder or placebo in three dosing phases: an initial clinically observed dose escalation of 0.5 to 6 mg peanut protein or placebo during 2 days; up-dosing every 2 weeks, starting at 3 mg and continuing for 20 to 40 weeks to a dose of 300 mg; and maintenance with 300 mg daily for at least 24 weeks.
"The first dose of each new level in the up-dosing schedule and first maintenance dose, like the initial dose escalation, are administered under supervision of a qualified healthcare professional in a healthcare setting," the FDA explained in its briefing document.
The study's primary efficacy outcome was the proportion of participants aged 4 through 17 years in the intent-to-treat (ITT) population who could tolerate a dose of 600 mg or more of peanut protein with mild symptoms at most during an exit DBPCFC at the conclusion of the maintenance period.
The study met its success criterion, a treatment difference of at least 15% between the study drug and placebo, for patients aged 4 through 17 years (treatment difference [efficacy] estimate of 63.2%; 95% confidence interval [CI], 53.0 – 73.3).
Those who did not undergo an exit DBPCFC were considered to have not responded with regard to the primary efficacy endpoint.
There was no significant treatment difference in the adult ITT population, a key secondary endpoint (efficacy estimate, 27.2%; 95% CI, –1.7 to 56.0).
Safety
The panel considered pooled safety data from ARC003 and ARC007. ARC007 was a randomized, controlled phase 3 clinical trial that assessed the safety of the peanut allergen powder in children aged 4 through 17 years.
"Unlike ARC003, ARC007 was designed to simulate clinical practice in that it did not require a positive DBPCFC to enroll in the study or require a food challenge at study end to assess efficacy," according to the FDA's briefing document. The study did not include a maintenance phase; participants reached the 300-mg daily dose and were discharged from the trial.
The patients who were treated with the peanut protein experienced a higher number of allergic reactions, including systemic allergic reactions, during initial dose escalation and up-dosing, compared with patients who received placebo (9.4% vs 3.8%). The same imbalance was observed during maintenance (8.7% vs 1.7%). During the maintenance phase, 7.7% of patients who received peanut allergen required epinephrine, compared with 3.4% of those who received placebo.
Temporary voting member John Kelso, MD, staff physician in allergy and immunology at the Scripps Clinic in San Diego, California, said he does not believe the effectiveness of the treatment has been demonstrated, "because the treatment itself represents a challenge every time a dose is given, and...patients who are on the treatment are twice as likely to have a reaction requiring epinephrine.
"[Efficacy] may be demonstrated on the day that particular food challenge is done, but over a longer period of time, when the patients are having a challenge every day in the form of a dose of medication, that actually increases rather than decreases their likelihood of a reaction," Kelso explained.
In the entire clinical development program, 12 patients in the peanut allergen group were diagnosed with eosinophilic esophagitis, whereas no patients in the placebo group of the controlled safety population were diagnosed with eosinophilic esophagitis.
Adverse events occurred in 53.0% of patients in the peanut allergen group compared with 31.8% of those in the placebo group. Most adverse events were mild. In the controlled safety population, the most frequent adverse events that occurred at a rate that was at least 5% higher in the peanut allergen recipients than in the placebo group were abdominal discomfort, throat irritation, itching, vomiting, cough, nausea, urticaria, oral pruritus, and sneezing. Adverse events decreased in frequency during the maintenance period compared with the up-dosing period.
If the drug is approved, the FDA will require a risk evaluation and mitigation strategy to address the risk for systemic allergic reactions, including anaphylaxis. That strategy will require that patients and their caregivers carry injectable epinephrine and administer "the initial dose escalation and the first dose of each up-dosing level...in a certified facility capable of treating systemic allergic reactions."
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Cite this: FDA Panel Backs First-in-Class Medication for Peanut Allergy - Medscape - Sep 16, 2019.
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