Aimmune Therapeutics Announces Phase 2 Extended Maintenance Data Supporting Safety and Tolerability Profile of AR101 for Peanut Allergy

VIENNA–(BUSINESS WIRE)–Aimmune Therapeutics, Inc. (NASDAQ:AIMT), a biopharmaceutical company
developing CODIT™ (Characterized Oral Desensitization
ImmunoTherapy) treatments for life-threatening food
allergies, today announced that new Phase 2 extended maintenance therapy
data from Aimmune’s lead product, AR101 for peanut allergy, showed that
the safety and tolerability profile improved with continued treatment,
particularly in a low-dose extended maintenance regimen.
Patients on the low-dose extended maintenance regimen of 300 mg of AR101
per day experienced few adverse events, which were primarily mild, and
no patients discontinued therapy. The results support the CODIT
maintenance regimen in the ongoing Phase 3 PALISADE trial of AR101,
which is enrolling peanut-allergic patients 4-55 years of age.
Rima A. Rachid, M.D., Assistant Professor of Pediatrics, Harvard Medical
School and Boston Children’s Hospital, Division of Allergy and
Immunology, discussed the data today in Vienna at the European Academy
of Allergy and Clinical Immunology (EAACI) Congress 2016 in a
late-breaking oral abstract presentation titled “The safety and
tolerability of AR101, an oral immunotherapy (OIT) pharmaceutical
formulation for peanut allergy, after more than one year of treatment:
Results from an ongoing Phase 2b clinical trial (ARC002), including
low-dose (300 mg/day) and high-dose (2,000 mg/day) regimens” (abstract
#2362).
“We now have data for treatment with AR101 for at least a year in all
patients and almost two years in some. We are seeing not only that most
side effects associated with AR101 are typically mild, manageable
gastrointestinal adverse events that happen early in up-dosing, but also
that the rate of related adverse events decreases substantially during
extended maintenance, particularly with low-dose maintenance,” said Dr.
Rachid. “From a clinical perspective, it is useful to consider these
longer-term safety and tolerability data, along with the strong efficacy
data for AR101 previously reported after up-dosing and after 12 weeks of
low-dose maintenance therapy, to make treatment decisions. The
predictability of knowing that related adverse events occur primarily
early in up-dosing would be an important factor for patient management
if this is confirmed in larger and longer studies.”
The data are from ongoing study of maintenance dosing in patients who
participated in Aimmune’s Phase 2 clinical trials of AR101. After
patients completed the initial portion of the Phase 2 trial — the
up-dosing regimen, followed by twelve weeks of low-dose, CODIT
maintenance therapy at a daily dose of 300 mg of AR101, and then the
subsequent double-blind, placebo-controlled food challenge (DBPCFC) —
they were offered the options of staying on low-dose (CODIT) maintenance
of 300 mg of AR101 per day or attempting up-dosing to a high-dose
maintenance target of 2,000 mg of AR101 per day.
All of the 40 patients who completed the initial portion of the Phase 2
trial volunteered to continue on extended maintenance therapy with
AR101. Of these, 11 elected to remain on CODIT maintenance therapy of
300 mg of AR101 per day, and 29 chose to attempt up-dosing to high-dose
maintenance therapy. The exposure-adjusted, treatment-related, adverse
event rate during extended maintenance for patients on CODIT maintenance
therapy was one every 574 days. The exposure-adjusted,
treatment-related, adverse event rate during extended maintenance for
patients on high-dose maintenance therapy was one every 107 days.
The 11 patients who elected to remain on CODIT 300 mg maintenance
therapy all remained in the study, and the few adverse events they
experienced were almost exclusively mild, with only one categorized as
moderate. No patients developed new-onset persistent gastrointestinal
symptoms and there were no treatment-related serious adverse events
(SAEs) during extended maintenance.
“Our most important objective is the safety of our patients. Our Phase 2
trials have shown that treatment with AR101 can reduce the risk of
severe allergic reactions to peanut and that tolerability improves over
time,” said Aimmune CEO Stephen Dilly, M.B.B.S., Ph.D. “Now we are
demonstrating that AR101’s safety and tolerability profile with
low-dose, extended maintenance therapy — our CODIT regimen — appears to
be quite acceptable. These data have also shown an advantage in extended
maintenance by minimizing peanut taste breakthrough, which we expect to
support compliance in patients who have peanut taste aversion.”
“These results reinforce the Phase 3 PALISADE trial design with the
CODIT regimen because, as we hypothesized, low-dose maintenance is
demonstrating to be better tolerated and is easier for patients to do
than high-dose maintenance,” continued Dr. Dilly. “PALISADE will also
give us the opportunity to test the expectation, based on academic
studies, that low-dose extended maintenance therapy with AR101 could
protect to even higher levels of peanut protein exposure than we saw
immediately after up-dosing in ARC001 and after 12 weeks of low-dose
maintenance therapy in ARC002.”
An early study of low-dose maintenance (Jones et al, 2009 [1])
and more recent work (Cronin et al, 2014 [2], and Vickery et al,
2015 [3]) have shown that a low, 300 mg daily maintenance dose of peanut
protein can achieve a high level of desensitization, as patients in
these studies were able to tolerate at least 2,100 mg and as much as
5,000 mg of peanut protein in food challenges administered after a year
or more of maintenance therapy.
Dr. Rachid also presented biomarker data from extended maintenance
therapy with AR101, which showed favorable changes with both low-dose
and high-dose extended maintenance, including diminishing peanut
skin-prick test wheal diameters, additional reductions in
peanut-specific IgE levels, and continued increases in peanut-specific
IgG4 levels.
“We are really excited to learn more from biomarker data in our Phase 3
PALISADE trial that is currently underway, along with other planned
studies,” said Dr. Dilly. “We hope to confirm the data demonstrated in
the Phase 2 study as well as our belief that it may be useful to look at
baseline peanut-specific IgE levels to help patients and physicians know
what to expect in terms of improving tolerability, and when adjunctive
therapies could potentially help. We are also planning to explore
signals that could point to sustained unresponsiveness.”
Conference Call on Monday, June 13, 2016, at 4 p.m. Eastern Time
Aimmune will host a conference call and live audio webcast on Monday,
June 13, 2016, at 4:00 p.m. Eastern Time to discuss the extended
maintenance data.
The conference call will be accessible via the company’s website at www.aimmune.com
on the Events page under Investor Relations. Please connect to the
company’s website at least 15 minutes prior to the start of the
conference call to ensure adequate time for any software download that
may be required to listen to the webcast. Alternatively, participants
may dial (877) 497-1438 (domestic) or (262) 558-6296 (international) and
refer to conference ID 27715872.
The archived conference call will be available on Aimmune’s website
beginning approximately two hours after the event and will be archived
and available for replay for at least 30 days after the event. For a
telephone replay, please dial (855) 859-2056 (domestic) or (404)
537-3406 (international) and refer to conference ID 27715872.
About Food Allergies
Food allergies are a significant and growing health problem in the
United States, Europe and throughout the developed world. It is
estimated that more than 30 million people in the United States and
Europe have a food allergy, and more than five million people in the
United States and Europe have peanut allergy, including more than two
million children. The prevalence of peanut allergy in children in the
United States is estimated to have tripled between 1997 and 2008, and
experts believe it has continued to rise since 2008. For people living
with food allergies, certain foods can cause severe allergic reactions,
including potentially life-threatening anaphylaxis. There are no
approved medical therapies to cure food allergies or prevent their
effects. Currently, food-allergic patients manage their condition by
strict allergen avoidance and carrying epinephrine auto-injectors for
use in case of accidental exposure. Thus, in addition to the unmet
medical need, food allergies can impose a significant quality-of-life
burden. For more information, please see www.foodallergy.org
and www.niaid.nih.gov/topics/foodallergy.
About AR101 and CODIT™
Aimmune Therapeutics is developing AR101 as a potential desensitization
therapy for patients with peanut allergy to provide them with protection
from reactions to peanut allergens at a level believed to substantially
exceed the amount typically encountered in an accidental exposure. AR101
maintains the complete range of natural peanut proteins, which are
rigorously analyzed and combined with pharmaceutical-grade ingredients
to ensure that each dose has consistent amounts of peanut protein with
well-defined concentrations of peanut allergens, especially the three
key allergenic proteins (Ara h1, h2 and h6). Patients ingest AR101 mixed
into small amounts of palatable, age-appropriate food.
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 (the randomized,
double-blind, placebo-controlled ARC001 trial and the ARC002
rollover/crossover trial), 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 73 percent, 65 percent, and 44 percent on an intent-to-treat basis
with n=55).
With the CODIT regimen, 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 the United States, Canada, and
the European Union.
About Aimmune Therapeutics
Aimmune Therapeutics, Inc., is a clinical-stage biopharmaceutical
company developing treatments for life-threatening food allergies. The
company’s Characterized Oral Desensitization ImmunoTherapy
(CODIT™) system, an approach to oral immunotherapy (OIT), uses
rigorously characterized product candidates with gradual, controlled
up-dosing protocols to obtain clinically meaningful desensitization to
food allergens. Aimmune’s first CODIT product, AR101 for the treatment
of peanut allergy, has received the FDA’s Breakthrough Therapy
Designation for the desensitization of peanut-allergic patients 4-17
years of age. Aimmune’s Phase 3 trial of AR101, PALISADE, is now
enrolling patients. For more information, please see www.aimmune.com.
References
[1] Clinical efficacy and immune regulation with peanut oral
immunotherapy. Jones, Stacie M. et al. Journal of Allergy and
Clinical Immunology, Volume 124, Issue 2, 292 – 300.e97
[2] Low Dose Maintenance Peanut Oral Immunotherapy Can Produce Sustained
Unresponsiveness. Cronin, Julia A. et al. Journal of Allergy and
Clinical Immunology, Volume 133, Issue 2, AB103
[3] High Rate of Sustained Unresponsiveness with Early-Intervention
Peanut Oral Immunotherapy. Vickery, Brian P. et al. Journal of
Allergy and Clinical Immunology, Volume 135, Issue 2, AB155.
Forward-Looking Statements
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 potential applications
of its CODIT™ system; Aimmune’s expectations on increasing compliance in
patients with peanut taste aversion; Aimmune’s expectations that
low-dose extended maintenance therapy with AR101 could protect to higher
levels of peanut exposure than were observed in ARC002; and Aimmune’s
plans to explore signals in AR101 that could point to sustained
unresponsiveness. Risks and uncertainties that contribute to the
uncertain nature of the forward-looking statements include: the
expectation that Aimmune will need additional funds to finance its
operations; 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
dependence on the success of AR101; 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
the United States and foreign countries; and Aimmune’s ability to
attract and retain senior management personnel. These and other risks
and uncertainties are described more fully in Aimmune’s most recent
filings with the Securities and Exchange Commission, including the
Quarterly Report on Form 10-Q for the period ended March 31, 2016, filed
on May 16, 2016. All forward-looking statements contained in this press
release speak only as of the date on which they were made. Aimmune
undertakes no obligation to update such statements to reflect events
that occur or circumstances that exist after the date on which they were
made.
This press release concerns a product that is under clinical
investigation and that has not yet been approved for marketing by the
U.S. Food and Drug Administration (FDA) or the European Medicines Agency
(EMA). It is currently limited to investigational use, and no
representation is made as to its safety or effectiveness for the
purposes for which it is being investigated.