Aimmune Therapeutics, Inc. announced the publication of new clinical data from a pooled analysis of three controlled phase 3 (PALISADE, RAMSES, ARTEMIS) and two open-label extension trials (ARC004, ARC011) of PALFORZIA® [Peanut (Arachis hypogaea) Allergen Powder-dnfp] in the Journal of Allergy and Clinical Immunology (JACI). PALFORZIA was approved as an oral immunotherapy (OIT) for the mitigation of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut for patients aged 4 to 17 years with a confirmed diagnosis of peanut allergy on January 31, 2020 by the U.S. Food and Drug Administration (FDA), on December 17, 2020 by the European Commission (EC), on April 7, 2021 by the Medicines and Healthcare products Regulatory Agency (MHRA) in the U.K., and on May 4, 2021 by Swissmedic. Use of PALFORZIA may be continued in patients 18 years of age and older.

PALFORZIA is not indicated for the emergency treatment of allergic reactions, including anaphylaxis and must always be used in conjunction with a peanut-avoidant diet. Key highlights from the analysis include: Across the controlled and open-label trials, 944 participants received =1 PALFORZIA dose and were subject to this analysis. 770 (83.8%) patients completed the updosing phase.

The exposure-adjusted adverse event (AE) rate was higher during the two-day initial dose escalation (IDE) (272.2 events/person-years exposure (PYE), n=944) and decreased to a rate of 14.9 events/PYE (n=45 at 79-91 weeks of 300-mg PALFORZIA treatment). The most frequently reported AEs, including treatment-related adverse events (TRAEs), adjusted for exposure, were primarily respiratory or GI in nature. Across all dosing phases (IDE and updosing), 497 (52.6%) PALFORZIA-treated participants experienced TRAEs with a maximum severity Common Toxicity Criteria for Adverse Events (CTCAE) grade of mild (grade 1), and 332 (35.2%) experienced TRAEs with a maximum severity of moderate (grade 2).

24 participants (2.5%) experienced TRAEs that were severe (grade 3). During the updosing phase, AEs of any severity were more common at lower PALFORZIA doses (3-80 mg) than higher doses (=120 mg). The rates of AEs during IDE and updosing were similar across the randomized, controlled PALISADE, RAMSES, and ARTEMIS trials.

Observation of in-clinic dosing revealed that onset and resolution of AEs occurred rapidly. Within the integrated populations, the median times from PALFORZIA administration to symptom onset varied from four to eight minutes; median times from onset of first symptom to resolution of last symptom varied between 15 to 30 minutes. In the controlled population, which included both active- and placebo-treated participants from PALISADE, RAMSES, and ARTEMIS, the use of epinephrine was higher in participants treated with PALFORZIA (n=80/841; 9.5%) than in participants treated with placebo (n=15/335; 4.5%).

Most events of epinephrine use occurred during IDE and updosing with both PALFORZIA and placebo. Episodes of AEs where epinephrine was administered were generally mild or moderate in severity, occurred primarily during the first six months of treatment, and only a single epinephrine dose was used. In the maintenance phases for PALISADE and ARTEMIS, the proportion of PALFORZIA-treated participants who received epinephrine was 7.7% (n=24/310) and 3.7% (n=4/108), respectively, and 3.4% (n=4/118) and 0% (n=0/41) of placebo-treated participants, respectively.

Across the controlled population, the proportion of participants reporting accidental peanut exposure was lower in the PALFORZIA group compared with placebo. Additionally, fewer participants in the active groups in PALISADE and ARTEMIS experienced AEs due to accidental peanut exposure requiring treatment compared with placebo during the maintenance period. None of the PALFORZIA-treated participants received epinephrine to treat the associated AEs following peanut allergen exposure whereas three placebo treated participants received epinephrine following accidental peanut exposure.

PALFORZIA is an oral immunotherapy indicated for the mitigation of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut. PALFORZIA is approved for use in patients with a confirmed diagnosis of peanut allergy. Initial Dose Escalation may be administered to patients aged 4 through 17 years.

Up-Dosing and Maintenance may be continued in patients 4 years of age and older. PALFORZIA is to be used in conjunction with a peanut-avoidant diet. Limitations of Use: Not indicated for the emergency treatment of allergic reactions, including anaphylaxis.