Aimmune Therapeutics’ Pivotal Phase 3 PALISADE Trial of AR101 Meets Primary Endpoint in Patients With Peanut Allergy
- Landmark 554-patient Phase 3 study met the primary efficacy endpoint, as 67.2% of AR101 patients ages 4–17 tolerated at least a 600-mg dose of peanut protein in the exit food challenge, compared to 4.0% of placebo patients (p<0.00001)
- The lower-bound of the 95% confidence interval (CI) of the difference between treatment arms at the primary endpoint was 53.0%, greatly exceeding the pre-specified threshold of 15% (p<0.00001)
- 50.3% of AR101 patients ages 4–17 tolerated a 1000-mg dose of peanut protein in the exit food challenge, compared to 2.4% of placebo patients (p<0.00001)
- Among patients ages 4–17 who completed treatment with AR101, 96.3% tolerated a 300-mg dose of peanut protein in the exit food challenge, 84.5% tolerated a 600-mg dose, and 63.2% tolerated a 1000-mg dose
- 79.6% of AR101 patients ages 4–17 completed the trial; of the 20.4% who discontinued treatment, 12.4% withdrew due to treatment-related adverse events
- 2.4% of AR101 patients ages 4–17 and 0.8% of placebo patients experienced serious adverse events
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PALISADE enrolled 499 patients ages 4–17, 496 of whom received treatment. After approximately one year of treatment, patients completed an exit double-blind, placebo-controlled food challenge (DBPCFC). In the primary analysis of 496 patients ages 4–17, 67.2% of AR101 patients tolerated a single highest dose of at least 600 mg of peanut protein (1043 mg cumulative) with no more than mild symptoms in the exit DBPCFC, compared to 4.0% of placebo patients. The corresponding difference in response rates was 63.2% (p<0.00001, 95% CI=53.0–73.3%), and, at 53%, the lower bound of the 95% confidence interval greatly exceeded the pre-specified success criterion, which was 15%. Additionally, 50.3% of AR101 patients tolerated a single highest dose of 1000 mg of peanut protein (2043 mg cumulative), compared to 2.4% of placebo patients (p<0.00001). In order to minimize the risk of assessment bias, the primary endpoint evaluations were conducted by independent, blinded assessors, who were not involved in patients’ ongoing care in the trial and who were blinded to treatment assignment and the sequence of the DBPCFCs.
Intent-to-Treat Efficacy: Percent of Patients Tolerating Each Dose in Exit DBPCFC1
|300 mg||600 mg||1000 mg|
|95% CI difference||(58.6–78.5%)||(53.0–73.3%)||(38.0–57.7%)|
1 Ages 4–17
Of patients ages 4–17, 296 patients (79.6%) from the AR101 arm completed the trial, compared to 116 patients (93.5%) from the placebo arm. Of these AR101 completers, 96.3% tolerated a single highest dose of at least 300 mg (443 mg cumulative) of peanut protein in the exit DBPCFC, 84.5% tolerated at least 600 mg (1043 mg cumulative), and 63.2% tolerated 1000 mg (2043 mg cumulative). Additionally, AR101 significantly reduced symptom severity at each exit DBPCFC dose level, compared to placebo.
Completer Efficacy: Percent of Patients Tolerating Each Dose in Exit DBPCFC1
|300 mg||600 mg||1000 mg|
|95% CI difference||(78.0–97.3%)||(69.7–90.6%)||(49.9–71.3%)|
1 Ages 4–17
PALISADE enrolled a highly allergic patient population, and enrollment was balanced for baseline disease characteristics between the two treatment arms. Patients in the primary analysis group of ages 4–17 tolerated no more than 30 mg of peanut protein in the entry DBPCFC; additionally, 72.2% had a past medical history of anaphylaxis, 53.0% had a present or previous diagnosis of asthma, and 65.5% reported multiple food allergies.
In the trial’s primary analysis group of ages 4-17, 496 patients from both arms (372 AR101 and 124 placebo) were evaluable for safety. In both arms, the incidence of serious adverse events (SAEs) was low. A total of 10 patients experienced SAEs, none of which were considered life-threatening: nine of these patients were in the AR101 arm (2.4%) and one was in the placebo arm (0.8%). Of the nine AR101 patients who experienced a SAE, five patients experienced mild or moderate SAEs. The other four AR101 patients experienced severe SAEs, which, for two of these patients, were not related to treatment (a concussion and a viral asthmatic exacerbation). Of the two patients who experienced severe SAEs related to treatment, both of whom had elevated baseline peanut-specific IgE levels greater than 100 kU/L, one experienced anaphylaxis, and the other experienced wheezing on the first day of treatment. Both of these patients discontinued from the study.
In ages 4–17, 20.4% of AR101 patients and 6.5% of placebo patients discontinued the trial. In the AR101 arm, 12.4% of patients discontinued due to investigator-reported adverse events, including 6.7% due to gastrointestinal adverse events and 2.7% due to systemic allergic hypersensitivity reactions. In the placebo arm, 2.4% of patients discontinued due to investigator-reported adverse events.
Discontinuations in the
|Total discontinuations regardless of causality||20.4%||76|
|Discontinuations not related to adverse events||8.0%||30|
|Discontinuations related to adverse events||12.4%||46|
• Systemic hypersensitivity reactions3
• Respiratory system
1 Ages 4-17
2 Includes one case of biopsy-confirmed eosinophilic esophagitis; no additional cases were identified in the study
3 Of these, seven were investigator-identified anaphylaxis events (one severe)
4 Includes one discontinuation for each: acute viral illness, eye pruritus, headache, and an unknown factor
One patient (an 11-year-old boy), with a baseline peanut-specific IgE level of 352 kU/L) was discontinued from the study after being found to have biopsy-confirmed, moderate eosinophilic esophagitis during the study. By the time the patient left the study, the symptoms had resolved. No additional cases of eosinophilic esophagitis were identified in the study.
Hypersensitivity reactions are an expected and common side effect of oral immunotherapy. In PALISADE patients ages 4–17, 14.5% of AR101 patients experienced systemic hypersensitivity reactions, and for 98.2% of those patients, the reactions were mild or moderate. In comparison, 3.2% of placebo patients experienced systemic hypersensitivity reactions, and for all of those patients, the reactions were mild or moderate.
Across all ages, there were no deaths or suspected, unexpected serious adverse reactions (SUSARs) in the trial.
PALISADE included 55 adult patients ages 18–49 who were randomized into the study, with 41 patients in the AR101 arm and 14 patients in the placebo arm. In the AR101 arm, 21 patients discontinued treatment, eight due to adverse events. In an exploratory analysis of this age group, 85% of AR101 patients who completed the study tolerated at least 600 mg of peanut protein in the exit DBPCFC, compared to 15% of placebo patients who completed the study.
“It’s exciting to see this large-scale study confirm that a
characterized approach to oral immunotherapy, in an appropriately
supervised clinical setting, holds promise for becoming an approved
“We want to express our heartfelt gratitude to everyone who supported
the PALISADE trial, especially the investigators and their teams, our
employees, and, above all, the patients and their families,” said
“We at Aimmune are enormously pleased with this result, but this success
really belongs to the entire food allergy community,” said Aimmune CEO
Aimmune expects to submit a Biologics License Application (BLA) for
AR101 with the
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PALISADE (Peanut ALlergy oral Immunotherapy Study
of AR101 for DEsensitization in children and adults) was
an international, randomized 3:1, double-blind, placebo-controlled,
Phase 3 trial of the efficacy and safety of AR101 in a Characterized
Oral Desensitization ImmunoTherapy (CODIT™)
approach in patients with peanut allergy. PALISADE enrolled 554
peanut-allergic patients ages 4–49 (499 ages 4–17) at more than 60
clinical sites in
Aimmune plans to present data from the PALISADE trial in a late-breaking
oral abstract presentation at the 2018
About Aimmune’s Phase 3
Aimmune has three active Phase 3 AR101 studies underway. The open-label
follow-on trial to PALISADE, ARC004, crossed PALISADE placebo patients
over to active treatment and rolled AR101 patients over to extended
maintenance, with different dose frequency intervals; Aimmune plans a
data cut from this trial in the third quarter of 2018. Aimmune expects
data from the RAMSES trial, taking place in
AR101 is a novel, investigational oral biologic drug for use in oral immunotherapy (OIT) in patients with peanut allergy. The drug, which is manufactured in accordance with current Good Manufacturing Practices (cGMP), has a characterized protein profile found in peanuts, analyzed to ensure consistent major allergen content. The amount of active ingredient in each AR101 capsule is controlled to ensure minimal variability of allergen content across doses of a given strength.
Statements contained in this press release regarding matters that are
not historical facts are “forward-looking statements” within the meaning
of the Private Securities Litigation Reform Act of 1995. Because such
statements are subject to risks and uncertainties, actual results may
differ materially from those expressed or implied by such
forward-looking statements. Such statements include, but are not limited
to, statements regarding: Aimmune’s expectations regarding the potential
benefits of AR101; Aimmune’s expectations regarding potential
applications of the CODIT™ approach to treating life-threatening food
allergies; Aimmune’s expectations regarding the availability of
additional AR101 data in
This press release concerns a product that is under clinical
investigation and that has not yet been approved for marketing by the