–Patients tolerated as much as 2,000 mg of peanut protein with fewer
adverse events —
–Favorable ongoing and notable immunological changes observed over
time–
LISBON, Portugal–(BUSINESS WIRE)–Aimmune Therapeutics, Inc. (Nasdaq: AIMT), a biopharmaceutical company
developing treatments for life-threatening food allergies, today
announced results from ARC004, an open-label, rollover study of the
landmark Phase 3 PALISADE trial, which showed that extending daily
therapy with AR101 by an additional 28 weeks led to improved
tolerability with lower numbers of adverse events compared to the
PALISADE therapeutic dosing period, an increase in the amount of peanut
that could be safely ingested, and continued immunomodulation to peanut
protein in most patients. AR101 is an investigational biologic drug for
use in oral immunotherapy as a treatment to reduce the frequency and
severity of allergic reactions following exposure to peanuts. These data
were presented here today in an oral session at the European Academy of
Allergy and Clinical Immunology (EAACI) Congress 2019 in Lisbon.
After continuing daily doses of AR101 for an additional 28 weeks, the
majority of patients enrolled in the follow-on study could tolerate
doses of at least 1,000 mg of peanut protein, and nearly half of all
AR101-treated patients tolerated the highest 2,000 mg dose during the
exit food challenge. Furthermore, patients enrolled in the study
continued to see meaningful immunological changes, reinforcing the
potential benefits of continued daily AR101 dosing after one year.
“The results of this follow-on study to the PALISADE trial demonstrate
that AR101 can produce favourable immunological changes over time,
matched by patients’ ability to tolerate higher doses of peanut protein,
thus reinforcing the rationale for continued daily dosing of AR101
beyond one year,” said Katharina Blümchen, M.D., Associated Professor
and consultant for Paediatric Pneumology and Allergology at the
University Hospital Frankfurt, Germany.
Of the AR101-treated patients in PALISADE who entered the open-label
extension study, which evaluated safety, tolerability and immunological
changes of continued daily or non-daily dosing with 300 mg of AR101, 110
were assigned to the daily dosing regimen, and 104 completed the
double-blind, placebo-controlled food challenge (DBPCFC) after 28 weeks.
Immunologic changes to peanut protein were compared at the end of the
PALISADE trial and the end of the extended dosing period using a peanut
skin prick test (SPT) and measurements of peanut-specific immunoglobulin
E (psIgE) and immunoglobulin G4 (Ig4), each a marker of immunologic
changes occurring during the desensitization process. After 28 weeks of
extended maintenance with AR101, results showed:
Ability to Tolerate Peanut Protein
- 79.8% could tolerate a 1,000 mg challenge dose.
- 49% could tolerate the highest challenge dose of 2,000 mg.
Safety
-
A reduction in adverse events overall with the same participants
experiencing the same types of adverse events as during the PALISADE
therapeutic dosing period and reporting at least one adverse event
(PALISADE 88.2% vs. ARC004 84.5%). -
The severity of adverse events (AEs) was similar across the two
studies, with the majority of symptoms reported to be mild in nature
(PALISADE 54.5% vs. ARC004 52.7%). -
Only 2% of patients enrolled discontinued treatment during the
extended maintenance period due to AEs.
Immune System Changes to Peanut Protein
-
Favorable immunological changes for the population of patients studied
continued during the additional daily dosing period, as confirmed by
reductions in the SPT wheal diameter and levels of psIgE and a
corresponding increase in IgG4; all reflecting a continued maturation
of the desensitization and immunomodulatory processes in response to
AR101. -
For an individual patient, the ability to tolerate more peanut protein
appeared to occur independently of the observed ongoing
immunomodulation associated with continued AR101 treatment. -
Study findings are consistent with reports that for an individual
patient psIgE and SPT levels are not necessarily predictive of a
patient’s ability to tolerate discrete amounts of peanut.
“These findings demonstrate that AR101 treatment extended into the
second year reduces adverse events, increases ability the ability to
tolerate even high levels of exposure to peanut protein over time, and
further modulates the immune response to peanut in most patients,” said
Daniel Adelman, M.D., Chief Medical Officer of Aimmune. “Moreover, these
results show that more than three out of four patients treated with
AR101 over a 12-month period could potentially benefit from continued
therapy, with the expectation of being able to increase their ability to
tolerate higher levels of peanut protein. These results should provide
some peace of mind to patients with peanut allergy and their families.”
About PALISADE and the ARC004 Follow-on Study
The international, randomized, double-blind, placebo-controlled Phase 3
PALISADE (Peanut Allergy oral Immunotherapy Study
of AR101 for Desensitization) trial evaluated the efficacy
and safety of AR101 in patients with peanut allergy. PALISADE was
conducted at 66 sites in 10 countries in North America and Europe. A
total of 496 patients ages 4 to 17 were randomized 3:1 to receive AR101
or placebo along with 55 adults ages 18 to 49 who were not part of the
primary analysis. To meet PALISADE’s inclusion criteria, patients could
tolerate no more than the 30-mg dose of peanut protein in an entry
double-blind, placebo-controlled food challenge (DBPCFC), which
consisted of consecutive doses of 1, 3, 10, 30 and 100 mg of peanut
protein, given 20 to 30 minutes apart, as tolerated without
dose-limiting symptoms. Patients enrolled in PALISADE underwent a dose
escalation period of approximately 22 weeks to reach a therapeutic dose
of 300 mg per day of AR101 or placebo, then continued with daily
maintenance at 300 mg per day of AR101 or placebo for approximately six
months. At that point, patients underwent an exit DBPCFC, which tested
consecutive doses of 3, 10, 30, 100, 300, 600 and 1,000 mg of peanut
protein, given 20 to 30 minutes apart, and associated with only mild
symptoms. Both the entry and exit DBPCFCs used an independent, blinded
assessor. Following the completion of the exit DBPCFC, patients were
unblinded and eligible to rollover or crossover into the follow-on
ARC004 clinical trial, as appropriate.
A subset of patients who completed the Phase 3 PALISADE trial were
eligible to enter ARC004, which evaluated safety, tolerability and
immunological changes of continued daily or non-daily dosing with 300 mg
of AR101. Immunologic changes to peanut protein were compared at the end
of the PALISADE trial and the end of the extended therapeutic period
using a peanut skin prick test and measurements of peanut-specific
immunoglobulin E (psIgE) and immunoglobulin G4 (Ig4).
Full results from the PALISADE trial were published in the New
England Journal of Medicine in November 2018.1
About Peanut Allergy
Peanut allergy is one of the most common food allergies, affecting more
than 6 million people in the U.S. and Europe, and reactions to peanut
are often severe and potentially life-threatening. Peanut allergy
usually persists into adulthood2,3,4, 5 and while rare,
accounts for the majority of deaths related to food allergy.6
There are no approved treatment options for peanut allergy.7
The standard of care has been a strict elimination diet and the timely
administration of rescue medications in case of an allergic reaction
from accidental exposure.8,9,10 Despite vigilance, accidental
exposures may occur11 and cause reactions of unpredictable
severity,12 leading to a lifelong risk of severe reactions.
About AR101
AR101 is a new, peanut-derived investigational oral biologic drug for
use in oral immunotherapy in patients with peanut allergy. The drug,
which is manufactured in accordance with current Good Manufacturing
Practices (cGMP), delivers a daily dose of peanut protein with a
consistent protein profile, analyzed to ensure reliable 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. AR101 is administered as an oral powder in
graduated doses in pull-apart capsules or foil-laminate sachets. The
contents are mixed thoroughly with a few spoonfuls of age-appropriate,
unheated food of the patient’s choice.
Aimmune’s Biologics License Application (BLA) for AR101 was accepted for
review by the U.S. Food and Drug Administration (FDA) in March 2019. The
Allergenic Products Advisory Committee (APAC) of the FDA will review the
BLA for AR101 at its meeting scheduled for September 13, 2019. The
Company plans to submit a Marketing Authorization Application (MAA) for
AR101 to the European Medicines Agency in mid-2019.
About Aimmune Therapeutics
Aimmune Therapeutics, Inc., is a biopharmaceutical company developing
oral treatments for life-threatening food allergies. The company’s Characterized
Oral Desensitization
ImmunoTherapy
(CODIT™) approach is intended to provide meaningful levels of protection
against allergic reactions resulting from exposure to food allergens by
desensitizing patients with defined, precise amounts of key allergens.
Aimmune’s first investigational biologic product, AR101, is being
developed as a treatment to reduce the frequency and severity of adverse
events, including anaphylaxis, following exposure to peanut. The BLA for
AR101 is under review by the U.S. FDA, which in 2015 granted AR101
Breakthrough Therapy Designation for the desensitization of
peanut-allergic patients 4 to 17 years of age. Aimmune expects to file
for marketing approval of AR101 in Europe in mid-2019. Aimmune has filed
an IND application for its second product, AR201 for the treatment of
egg allergy, and intends to start a randomized phase 2 clinical trial in
mid-2019. For more information, please see www.aimmune.com.
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 expectations regarding the potential
benefits of AR101, including the potential benefit of continued therapy;
Aimmune’s expectations regarding the review of the BLA for AR101 by the
FDA and APAC; Aimmune’s expectations regarding the planned timing and
filing for marketing approval of AR101 in Europe; Aimmune’s expectations
on the timing of initiating a phase 2 clinical trial for AR201; and
Aimmune’s expectations regarding potential applications of the CODIT™
approach to treating life-threatening food allergies. Risks and
uncertainties that contribute to the uncertain nature of the
forward-looking statements include: Aimmune’s or any of its
collaborative partners’ ability to initiate and/or complete clinical
trials; the unpredictability of the regulatory process; the possibility
that Aimmune’s or any of its collaborative partners’ clinical trials
will not be successful; Aimmune’s dependence on the success of AR101;
Aimmune’s reliance on third parties for the manufacture of Aimmune’s
product candidates; 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 its Quarterly
Report on Form 10-Q for the quarter ended March 31, 2019. 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 AR101, a product candidate that is under
clinical investigation, and AR201, a product candidate that Aimmune
expects will be under clinical investigation in 2019. Neither AR101 nor
AR201 has been approved for marketing by the FDA or the European
Medicines Agency (EMA). AR101 and AR201 are currently limited to
investigational use, and no representation is made as to their safety or
effectiveness for the purposes for which they are being investigated.
References
1 Vickery BP, Vereda A, Casale TB, et al. AR101 oral
immunotherapy for peanut allergy. New Engl J Med. 2018; DOI:
10.1056/NEJMoa1812856.
2 Crespo JF, James JM,
Fernandez-Rodriguez C, Rodriguez J. Food allergy: nuts and tree nuts. Br
J Nutr. 2006; 96:Suppl 2:S95-S102.
3 Moreno MA.
Guidelines for children with peanut allergy. JAMA Pediatr.
2017;171:100.
4 Skolnick HS, Conover-Walker MK, Koerner
CB, Sampson HA, Burks W, Wood RA. The natural history of peanut allergy. J
Allergy Clin Immunol. 2001;107:367-74.
5 Fleischer
DM, Conover-Walker MK, Christie L, Burks AW, Wood RA. The natural
progression of peanut allergy: resolution and the possibility of
recurrence. J Allergy Clin Immunol. 2003;112:183-9.
6
Bock SA, Muñoz-Furlong A, Sampson HA. Fatalities due to anaphylactic
reactions to foods. J Allergy Clin Immunol. 2001;107:191-3.
7
Yu W, Freeland DMH, Nadeau KC. Food allergy: immune mechanisms,
diagnosis and immunotherapy. Nat Rev Immunol. 2016;16:751-65.
8
Boyce JA, Assa’ad A, Burks AW, et al. Guidelines for the diagnosis and
management of food allergy in the United States: report of the
NIAID-sponsored expert panel. J Allergy Clin Immunol.
2010;126:Suppl:S1-S58.
9 Sampson HA, Aceves S, Bock SA,
et al. Food allergy: a practice parameter update — 2014. J Allergy
Clin Immunol. 2014;134(5):1016-25.e43.
10 Muraro A,
Werfel T, Hoffmann-Sommergruber K, et al. EAACI food allergy and
anaphylaxis guidelines: diagnosis and management of food allergy. Allergy.
2014;69:1008-25.
11 Rimbaud L, Heraud F, La Vieille S,
Leblanc J-C, Crépet A. Quantitative risk assessment relating to the
inadvertent presence of peanut allergens in various food product. Int
Food Risk Anal J. 2013;3:1-11.
12 Allen KJ,
Remington BC, Baumert JL, et al. Allergen reference doses for
precautionary labeling (VITAL 2.0): clinical implications. J Allergy
Clin Immunol. 2014;133:156-64.
Contacts
Investors:
Eric Bjerkholt
(650) 376-5582 or
ebjerkholt@aimmune.com
Media:
Jerica Pitts
(312) 858-3469
jpitts@w2ogroup.com
Louise Strong
+44 203 808 6471
lstrong@w2ogroup.com