Allakos Inc. (the “Company” or “Allakos”) (Nasdaq: ALLK), a
biotechnology company developing lirentelimab (AK002) for the
treatment of eosinophil and mast cell-related diseases, today
reported data from ENIGMA 2, a 24-week Phase 3 randomized,
double-blind, placebo-controlled study of lirentelimab in patients
with biopsy confirmed eosinophilic gastritis (EG) and/or
eosinophilic duodenitis (EoD) and KRYPTOS, a 24-week Phase 2/3
randomized, double-blind, placebo-controlled study of lirentelimab
in patients with biopsy-confirmed eosinophilic esophagitis (EoE).
Both ENIGMA 2 and KRYPTOS studies met their histologic co-primary
endpoints, but did not achieve statistical significance on the
patient reported symptomatic co-primary endpoints.
“We are deeply disappointed that the studies did not achieve
their symptomatic endpoints,” said Robert Alexander, PhD,
Chief Executive Officer of Allakos. “The company is grateful
to the patients with eosinophilic gastrointestinal diseases (EGIDs)
and to the investigators who participated in the ENIGMA and KRYPTOS
trials.”
Dr. Craig Paterson, MD, Chief Medical Officer of Allakos added,
“Although the EGID results are surprising and disappointing, we
will continue to analyze the data to understand the results and to
determine the path forward for lirentelimab in EGIDs. At present we
intend to continue our development efforts with subcutaneous
lirentelimab in atopic dermatitis, chronic spontaneous urticaria,
and asthma. The atopic dermatitis study is underway and we plan to
initiate chronic spontaneous urticaria and asthma studies in 2022
and will continue to advance other programs in our preclinical
pipeline.”
ENIGMA 2 Phase 3 Topline Results
The co-primary endpoints for the Phase 3 study were (1) the
proportion of patients achieving histologic resolution (defined as
≤4 eosinophils (eos) / high powered field (hpf) in 5 hpfs in the
stomach and/or ≤15 eos/hpf in 3 hpfs in the duodenum) and (2)
symptomatic improvement as measured by absolute change in the six
symptom total symptom score (TSS).
Co-Primary Endpoints |
Lirentelimab (n=91) |
Placebo (n=89) |
Histology Endpoint: Proportion of responders as determined by
gastric or duodenal tissue eosinophil counts1 |
84.6%(p<0.0001) |
4.5% |
Symptom Endpoint: Absolute mean change in patient reported Total
Symptom Score (TSS-6)2 |
Baseline TSS: 29.5 |
Baseline TSS: 27.7 |
-10.0 (p=0.343) |
-11.5 |
1 = A responder is a patient achieving the following peak
eosinophil counts: eosinophil count ≤4 cells per hpf in 5 gastric
hpf and/or eosinophil count ≤15 cells per hpf in 3 duodenal hpf.
Endpoint assessed at end of Week 24.2 = TSS-6 is daily patient
reported symptom questionnaire assessing 6 symptoms (abdominal
pain, nausea, bloating, early satiety, abdominal cramping, and loss
of appetite) on a scale from 0 to 10. Endpoint assessed as mean
change from baseline to Weeks 23-24.
The safety results of the trial were generally consistent with
previously reported lirentelimab studies. No new safety signals
were observed. Mild to moderate infusion-related reactions
(including flushing, feeling of warmth, headache, nausea, and/or
dizziness) occurred in 34% of lirentelimab-treated patients and 14%
of placebo-treated patients.
KRYPTOS Phase 2/3 Topline Results
The co-primary endpoints for the Phase 2/3 study were (1) the
proportion of patients achieving histologic resolution (defined as
≤6 eosinophils (eos) / high powered field (hpf) in the esophagus)
and (2) symptomatic improvement as measured by absolute change in
dysphagia symptom questionnaire (DSQ).
Co-Primary Endpoints |
LirentelimabHigh Dose (n=91) |
LirentelimabLow Dose (n=93) |
Placebo (n=92) |
Histologic Endpoint: Proportion of responders (eos ≤6 /hpf) as
determined by esophageal tissue eosinophil counts 1 |
87.9%(p<0.0001) |
92.5% (p<0.0001) |
10.9% |
Symptom Primary Endpoint: Absolute mean change in patient reported
Dysphagia Symptom Questionnaire (DSQ)2 |
DSQ Baseline:34.2 |
DSQ Baseline:36.4 |
DSQ Baseline:35.2 |
-17.4(p=0.237) |
-11.9(p=0.247) |
-14.6 |
1 = A responder is a patient achieving the following peak
eosinophil counts: ≤6 eosinophils (eos) / high powered field (hpf)
in 1 hpf in the esophagus. Endpoint assessed at end of Week 24.2 =
DSQ is a patient reported symptom questionnaire assessing
difficulty swallowing. Endpoint assessed as absolute mean change
from baseline to Weeks 23-24.
The safety results of the trial were generally consistent with
previously reported lirentelimab studies. No new safety signals
were observed. Mild to moderate infusion-related reactions
(including flushing, feeling of warmth, headache, nausea, and/or
dizziness) occurred in 39% of high dose lirentelimab- treated
patients, 26% of low dose lirentelimab-treated patients and 12% of
placebo-treated patients.
Phase 3 ENIGMA 2 Study Design
The randomized, double-blind, placebo-controlled Phase 3 trial
of intravenous lirentelimab enrolled 180 patients with EG and/or
EoD. Patients were required to be moderately to severely
symptomatic based on a patient reported symptom questionnaire and
have biopsy-confirmed eosinophilia of the stomach (≥30
eosinophils/hpf in 5 hpfs) and/or duodenum (≥30 eosinophils/hpf in
3 hpfs). Patients were randomized 1:1 to receive: 1.0 mg/kg of
lirentelimab for the first month followed by five doses of 3.0
mg/kg given monthly or (b) a monthly placebo. Disease symptoms were
measured daily using a patient reported symptom questionnaire that
scored 6 symptoms (abdominal pain, nausea, bloating, early satiety,
abdominal cramping, loss of appetite) each on a scale from 0 to 10
(TSS). Co-primary endpoints were (1) proportion of responders with
≤4 eos/hpf in 5 hpfs in the stomach and/or ≤15 eos/hpf in 3 hpfs in
the duodenum at the end of week 24 and (2) absolute change from
baseline in TSS at weeks 23-24.
Phase 2/3 KRYPTOS Study Design
The randomized, double-blind, placebo-controlled Phase 2/3 trial
of intravenous lirentelimab enrolled 276 patients with EoE.
Patients were required to be moderately to severely symptomatic
based on the dysphagia symptom questionnaire (DSQ) and have
biopsy-confirmed eosinophilia of the esophagus (≥15 eosinophils in
1 hpf). Patients were randomized 1:1:1 to receive: 1.0 mg/kg of
lirentelimab for the first month followed by five doses of 3.0
mg/kg given monthly (b) monthly 1.0 mg/kg of lirentelimab (c) a
monthly placebo. Disease symptoms were measured daily using a
patient reported symptom questionnaire that assessed difficulty
swallowing. Co-primary endpoints were (1) proportion of responders
with ≤6 eosinophils in 1 hpf in the esophagus and (2) absolute
change in dysphagia symptom questionnaire from baseline.
About Allakos
Allakos is a clinical stage biotechnology company developing
antibodies that target immunomodulatory receptors present on immune
effector cells involved in allergic, inflammatory, and
proliferative diseases. The Company’s lead antibody, lirentelimab
(AK002), is an investigational medicine that is being evaluated in
clinical studies, including in EGIDs and a Phase 2 study in atopic
dermatitis. The Company plans to initiate a Phase 2/3 study in
chronic spontaneous urticaria and a Phase 2 study in asthma in the
middle of 2022 and Q4 2022, respectively. Lirentelimab targets
Siglec-8, an inhibitory receptor selectively expressed on human
eosinophils and mast cells. Inappropriately activated eosinophils
and mast cells have been identified as key drivers in a number of
severe diseases affecting the gastrointestinal tract, eyes, skin,
lungs and other organs. For more information, please visit the
Company's website at www.allakos.com.
Forward Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of 1995
as contained in Section 27A of the Securities Act of 1933, as
amended, and Section 21E of the Securities Exchange Act of 1934, as
amended. Such forward-looking statements include, but are not
limited to, Allakos’ progress and business plans, the expected
timing of anticipated study results and plans relating to its
future clinical trials. Such statements are subject to numerous
important factors, risks and uncertainties that may cause actual
events or results to differ materially from current expectations
and beliefs, including but not limited to: Allakos’ stages of
clinical drug development; Allakos’ ability to timely complete
clinical trials for, and if approved, commercialize lirentelimab
(AK002), its lead compound; Allakos’ ability to obtain required
regulatory approvals for its product candidates; uncertainties
related to the enrollment of patients in its clinical trials;
Allakos’ ability to demonstrate sufficient safety and efficacy of
its product candidates in its clinical trials; uncertainties
related to the success of later-stage clinical trials, regardless
of the outcomes of preclinical testing and early-stage trials;
market acceptance of Allakos’ product candidates; uncertainties
related to the projections of the size of patient populations
suffering from the diseases Allakos is targeting; Allakos’ ability
to advance additional product candidates beyond lirentelimab;
Allakos’ ability to obtain additional capital to finance its
operations; and other important risk factors set forth in Allakos’
most recent Annual Report on Form 10-K filed with the SEC on March
1, 2021, Quarterly Report on Form 10-Q filed with the SEC on
November 8, 2021, and future reports to be filed with the SEC.
These documents contain and identify important factors that could
cause the actual results for Allakos to differ materially from
those contained in Allakos’ forward-looking statements. Any
forward-looking statements contained in this press release speak
only as of the date hereof, and Allakos specifically disclaims any
obligation to update any forward-looking statement, except as
required by law. These forward-looking statements should not be
relied upon as representing Allakos’ views as of any date
subsequent to the date of this press release.
Investor Contact:Adam Tomasi, President and COOAlex Schwartz, VP
Strategic Finance and Investor Relationsir@allakos.com
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