Aimmune Therapeutics Presents Data on Biomarkers and Potential to Predict Response to Peanut Allergy Treatment With AR101
— Aimmune Discussed Phase 2 Data, Including Peanut-Specific IgE Values, at FARE Research Retreat —
“It was particularly pleasing to share these important findings with
many of the same food allergy leaders whose vision to pursue
All 55 patients who entered the ARC001 and ARC002 Phase 2 trials had documented psIgE values at pre-treatment baseline: 28 had values above 100 kUA/l and 27 had values of 100 kUA/l or less. In the 27 patients with psIgE ≤100 kUA/l, there were no treatment-related withdrawals, no serious adverse events, and no epinephrine use, and all patients met the primary endpoint at the double-blind, placebo-controlled food challenge administered at the end of up-dosing. There was a single withdrawal from this group due to scheduling issues. Conversely, in the 28 patients from the higher psIgE group, there were 10 treatment-related withdrawals and one patient failed the exit challenge, giving an overall treatment success rate of 61 percent in this group.
Other baseline measures, including skin prick test and maximum tolerated dose at entry double-blind, placebo-controlled food challenge, were not conspicuously different between patients who completed up-dosing and those who discontinued treatment during up-dosing.
“If replicated in our ongoing Phase 3 PALISADE trial, we believe that these findings could have very positive implications for the adoption of AR101 in clinical practice,” continued Dr. Dilly. “According to the published scientific literature, at least 80 percent of untreated people with peanut allergy have psIgE levels below 100 kUA/l, and, importantly, there seems to be no clear correlation between psIgE levels and reaction threshold or severity of reaction.”
“Our Phase 2 data suggest that peanut-specific IgE levels could play an
important role in identifying patients at increased risk for side
effects, particularly gastrointestinal side effects, from oral
immunotherapy. We are eager to see if this pattern around
peanut-specific IgE levels will be confirmed in our Phase 3 PALISADE
trial. If it is, we believe that a simple predictive test could
ultimately help guide the course of oral immunotherapy,” said Aimmune’s
Chief Medical Officer,
As previously reported, treatment with AR101 was associated with significantly increased peanut-specific IgG4 antibodies and a significantly decreased ratio of psIgE to IgG4. Also, the median peanut skin prick test wheal size declined meaningfully from measurements taken before treatment to those taken after patients had completed the AR101 up-dosing regimen.
In a separate presentation at the Research Retreat, Erik Wambre, Ph.D.,
“These data are extremely encouraging because they demonstrate that the reduction in clinical reactivity following treatment with AR101 is clearly linked to reduction of the pathogenic T cells associated with peanut allergy, and other quantifiable changes in the immune repertoire,” said Dr. Wambre. “We look forward to better understanding the ability of AR101 to reprogram the immune system by expanding our studies — not only in T cells but also B cells, basophils, and antibodies — in many more participants from Aimmune’s ongoing Phase 3 trial. It is exciting to be a part of the biggest peanut immunotherapy study ever undertaken because the large sample will give us unprecedented power to detect biomarkers of treatment response.”
About Food Allergies
Food allergies are a significant and growing health problem in
About AR101 and CODIT™
AR101 is part of Aimmune’s approach to treating food allergies using its Characterized Oral Desensitization ImmunoTherapy, or CODIT™, system. The CODIT system leverages extensive independent scientific research on oral immunotherapy, or OIT, demonstrating that food allergy patients can be desensitized to food allergens by being administered well-defined, gradually increasing doses of the allergen over a period of months. Aimmune’s CODIT system is designed to precisely control the amounts of the allergens administered in a systematic dosing regimen, beginning with very low doses of the allergens. Once a patient attains a clinically meaningful level of desensitization, the patient continues to take a daily maintenance dose of the CODIT system product in order to maintain the desensitization.
About Aimmune’s Phase 2 and Phase 3 Clinical Trials
Of the 55 patients who entered Aimmune’s Phase 2 trials (ARC001 and the ARC002 rollover/crossover), 44 patients completed the approximately six-month up-dosing period to a daily dose of 300 mg of AR101. At the end of that period, 43 of those patients tolerated a cumulative amount of 443 mg of peanut protein in a double-blind, placebo-controlled food challenge (DBPCFC). Additionally, 35 of the patients who completed up-dosing tolerated a cumulative amount of 1,043 mg of peanut protein in the DBPCFC, the highest challenge administered at that point. The patients who tolerated at least 443 mg of peanut protein in the post–up-dosing DBPCFC were eligible to continue on 300 mg of AR101 per day in maintenance therapy. After three months of maintenance, the patients (n=40) underwent another DBPCFC, where 100 percent, 90 percent, and 60 percent of patients tolerated cumulative amounts of peanut protein of 443 mg, 1,043 mg, and 2,043 mg, respectively (corresponding to 72 percent, 65 percent, and 44 percent on an intent-to-treat basis with n=55).
Approximately 90 percent of the treatment-related adverse events in Phase 2 have been mild, predominantly allergic, symptoms, consistent with stimulation of the immune system. There have been no treatment-related severe adverse events. One serious adverse event of moderate, non-life-threatening anaphylaxis occurred in Phase 2 early in the course of up-dosing. Ten patients discontinued from the trial for treatment-related reasons, all due directly or indirectly to gastrointestinal adverse events experienced early in the up-dosing regimen. These events typically occurred within the first few weeks of the treatment, and in all cases the symptoms resolved within three weeks of the cessation of treatment.
The primary endpoint in Aimmune’s currently enrolling Phase 3 PALISADE
trial of AR101 is tolerating a cumulative amount of at least 1,043 mg of
peanut protein after approximately six months of up-dosing and six
months of maintenance therapy at a daily dose of 300 mg of AR101.
PALISADE is a randomized 3:1, double-blind, placebo-controlled trial
expected to enroll approximately 500 peanut-allergic patients 4-55 years
of age at more than 60 clinical sites in
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 development efforts; Aimmune’s
expectations regarding the potential benefits of AR101; Aimmune’s
ability to use biomarkers to predict prospectively how patients will
react to AR101; Aimmune’s expectations regarding expanding its
partnership with BRI and conducting additional studies; and Aimmune’s
expectations regarding potential applications of its CODIT™ system.
Risks and uncertainties that contribute to the uncertain nature of the
forward-looking statements include: Aimmune’s ability to initiate and/or
complete clinical trials; the unpredictability of the regulatory
process; the possibility that Aimmune’s clinical trials will not be
successful; Aimmune’s reliance on third parties for the manufacture of
its product candidates and the conduct of its Phase 3 clinical trial for
AR101; possible regulatory developments in
This press release concerns a product that is under clinical
investigation and that has not yet been approved for marketing by the