By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved the first immunotherapy drug for the mitigation of peanut allergy. The drug is an oral immunotherapy, which represents the first approved therapy for treating any food allergy. Peanut powder oral immunotherapy (POIT) is made from defatted peanut flour and formulated as capsules and sachets.
POIT is indicated for the mitigation of allergic reaction, including prophylaxis that may occur with accidental exposure to peanuts.1 It is approved for use in patients with confirmed diagnosis of peanut allergy. POIT should be used with a peanut-avoidant diet.1
Treatment with POIT is administered in three sequential phases: initial dose escalation, up-dosing, and maintenance.1 Escalation may start for patients age 4-17 years. Up-dosing and maintenance may continue for patients ≥ 4 years of age. The initial dose escalation involves five daily doses of 0.5 mg, 1 mg, 1.5 mg, 3 mg, and 6 mg (in five blisters). Up-dosing is a 22-week escalation from 3 mg daily to 300 mg daily. The daily maintenance dose is 300 mg daily. Injectable epinephrine should be prescribed. Patients should be observed in a healthcare setting after administration of the initial dose escalation and the first dose of each up-dosing level. Treatment should be discontinued if the patient cannot tolerate doses up to and including the initial 3 mg dose. POIT is available as 0.5 mg, 1 mg, 10 mg, 20 mg, and 100 mg capsules and 300 mg sachets.
This is the first FDA-approved oral immunotherapy for desensitizing peanut allergy in children to help reduce the risk of allergic reactions.
POIT can cause anaphylaxis (9.4% vs. 3.8% for placebo), which can occur at any time during therapy.1 It should not be given to patients with uncontrolled asthma or a history of eosinophilic esophagitis.1 The most frequently reported adverse reactions (> 30% vs. placebo) that occurred in the up-dosing phase included abdominal pain (67% vs. 35%), vomiting (36% vs. 16%), nausea (32% vs. 14%), oral pruritus (31% vs. 10%), throat irritation (40% vs. 17%), cough (32% vs. 23%), and skin pruritus (32% vs. 20%).1 Overall, 11.6% of subjects in an active group withdrew from a study vs. 2.4% in a placebo group.2
The logistics of POIT administration are challenging. These include a 23-week initial and up-dosing period, an observation period during and after initial dose escalation (20-30 minutes), and between the first dose and first dose of each up-dosing level (for at least 60 minutes) under supervision of a healthcare professional. Daily maintenance is required to maintain effect.1 Powder should be consumed with a meal and delayed after exercise and hot water exposure (shower, bath) and during illness (e.g., viral illness).
The efficacy of POIT was evaluated in a randomized, double-blind, placebo-controlled study that included 551 subjects with peanut allergy (to ≥ 100 mg of peanut protein) age 4-55 years.1,2 Subjects were randomized to POIT (n = 416) in an escalating-dose program or placebo (n = 139). The primary endpoint was the percent of subjects who could tolerate a single dose of 600 mg peanut protein in an exit double-blind, placebo-controlled food challenge with no more than mild allergic symptoms after six months of maintenance treatment. Subjects who did not reach 300 mg/day were considered nonresponders. Key secondary endpoints included response rate after a single dose of 300 mg and 1,000 mg of peanut protein.
No statistically significant benefit was observed in subjects age 18-55 years. In the age 4-17 years group (n = 496), response rates for the intent-to-treat (at least one dose of study drug) analysis for 600 mg, 300 mg, and 1,000 mg were 67.2%, 76,6%, and 50.3%, respectively, compared to 4.0%, 8.1%, and 2.4%, respectively, for placebo. For those who completed the study (n = 296 for POIT and n = 116 for placebo), response rates for POIT were 84.5%, 96.3%, and 63.2% compared to 4.3%, 8.6%, and 2.6% for placebo.
An open-label, long-term, safety and tolerability, three-year study is in progress. Completion is expected by December 2024.3 Peanut sublingual and epicutaneous immunotherapy also has been investigated.4
Approximately 1 million children in the United States are allergic to peanuts, with only 20% outgrowing their allergy.5 The primary way to avoid severe and potentially life-threatening reactions is strict avoidance. Peanut oral immunotherapy offers an agent to desensitize an individual against accidental exposure up to 1,000 mg in some individuals age 4-17 years. Many allergists offer desensitization therapy with commercially available peanut flour, but POIT is the only FDA-approved treatment. POIT is only available through the Palforzia Risk Evaluation and Mitigation Strategy. The drug costs $890 for a 30-day 300 mg maintenance dose.
- Aimmune Therapeutics, Inc. FDA approves Aimmune’s Palforzia as first treatment for peanut allergy, Jan. 31, 2020. Available at: http://bit.ly/37XZwkW. Accessed Feb. 24, 2020.
- PALISADE Group of Clinical Investigators; Vickery BP, Vereda A, Casale TB, et al. AR101 oral immunotherapy for peanut allergy. N Engl J Med 2018;379:1991-2001.
- ClinicalTrials.gov. Long-term safety study of AR101 in subjects who participated in a prior AR101 study (ARC008). Available at: http://bit.ly/2vXk8g2. Accessed Feb. 24, 2020.
- Kim EH, Patel C, Burks AW. Immunotherapy approaches for peanut allergy. Expert Rev Clin Immunol 2020;16:167-174.
- U.S. Food & Drug Administration. FDA approves first drug for treatment of peanut allergy for children, Jan. 31, 2020. Available at: http://bit.ly/2Tanqo7. Accessed Feb. 24, 2020.