Aclaris Therapeutics Announces Preliminary Topline Data from 12-Week Phase 2a Study of Oral Zunsemetinib (ATI-450) for Moderate to Severe Hidradenitis Suppurativa
March 06 2023 - 7:00AM
Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage
biopharmaceutical company focused on developing novel drug
candidates for immuno-inflammatory diseases, today announced
preliminary topline results from a 12-week, Phase 2a, multicenter,
randomized, placebo-controlled clinical study to investigate the
efficacy, safety, tolerability, pharmacokinetics (PK) and
pharmacodynamics (PD) of zunsemetinib (ATI-450), an investigational
oral MK2 inhibitor, in patients with moderate to severe
hidradenitis suppurativa (HS) (ATI-450-HS-201).
EfficacyThe study did not meet its primary
endpoint of change from baseline in inflammatory nodule/abscess
count (AN) of zunsemetinib 50mg BID versus placebo at week 12. The
study also did not meet the secondary efficacy endpoints assessed
in the topline data, including percentage of patients achieving
HiSCR-50. The placebo effect observed across all efficacy endpoints
was higher than what has been observed in other published HS
studies reported to date.
SafetyZunsemetinib was generally well
tolerated. Safety findings were generally consistent with
observations from prior clinical studies of zunsemetinib. The most
common treatment-emergent adverse events in patients treated with
zunsemetinib were dizziness (16.7%), diarrhea (12.5%), headache
(12.5%), creatine phosphokinase (CPK) elevation (10.4%) and acne
(10.4%), with a majority deemed mild to moderate in severity.
Dizziness, diarrhea, headache and CPK elevation were generally
transient in nature. Thirty-seven patients discontinued study
treatment (22 on zunsemetinib and 15 on placebo), with 15 patients
discontinuing treatment due to AEs (11 on zunsemetinib and 4 on
placebo). No serious adverse events and no serious and/or
opportunistic infections were observed with patients treated with
zunsemetinib.
Pharmacokinetics/PharmacodynamicsPK and PD were
generally consistent with observations from prior clinical studies
of zunsemetinib. A preliminary analysis of endogenous plasma
cytokines and chemokines in patients with a confirmed dose of study
treatment on the day of blood draw, demonstrated zunsemetinib
dependent inhibition relative to placebo. Of the proinflammatory
markers that were elevated at baseline relative to healthy donors,
including IL6, IL8 and MIP1b, treatment-related median inhibition
trends were observed across the 12-week dosing period. While the
proinflammatory cytokine IL12/23p40 was not elevated at baseline
relative to healthy donors, a median inhibition trend was observed
in patients treated with zunsemetinib. In the subset of patients
with quantifiable IL17A/F levels at baseline, the cytokine was
elevated relative to healthy donors and an inhibition trend was
observed with zunsemetinib treatment. Endogenous TNFα plasma levels
were not elevated relative to healthy donors yet a small inhibition
trend was observed in treated patients. The anti-inflammatory
cytokine IL1RA was elevated at baseline and treatment-related
inhibition was not observed.
“We are incredibly grateful to the patients, investigators, our
internal study team and all others who contributed to the execution
of this clinical trial,” stated Doug Manion, M.D. Aclaris’ Chief
Executive Officer. “Despite not producing the efficacy results we
had hoped for in this particularly challenging disease, we are
encouraged by the consistent demonstration of zunsemetinib’s
mechanism of action and the strengthening of our safety data base
and continue to look forward to our next data read out of our Phase
2b study of zunsemetinib in patients with moderate to severe
rheumatoid arthritis.”
About ATI-450-HS-201 Phase 2a Study
(NCT05216224)
ATI-450-HS-201 is a randomized, double-blind,
placebo-controlled, multi-center Phase 2a study to investigate the
efficacy, safety, tolerability, PK and PD of zunsemetinib (50 mg
twice daily) in patients with moderate to severe HS. The study
enrolled 95 patients who were randomized 1:1 to zunsemetinib (n=48)
or placebo (n=47) across 19 clinical study sites in the US. The
primary endpoint of the study is change from baseline in
inflammatory nodule/abscess count at week 12. The topline efficacy
analyses are based on the full analysis set. Healthy volunteer
samples for PD analyses were obtained outside of the clinical trial
setting.
About Zunsemetinib
(ATI-450)
Zunsemetinib is an investigational oral mitogen-activated
protein kinase-activated protein kinase 2 (MK2) inhibitor. This
mechanism potentially leads to the inhibition of multiple
cytokines, chemokines, matrix metalloproteases and other
inflammatory signals. Key inflammatory cytokines driven by this
mechanism include TNFα and interleukin-1α, -1β, -6, -8 and -17
(IL1α, IL1β, IL6, IL8 and IL17). Aclaris is developing zunsemetinib
as a potential treatment for rheumatoid arthritis and psoriatic
arthritis.
About Aclaris Therapeutics, Inc.
Aclaris Therapeutics, Inc. is a clinical-stage biopharmaceutical
company developing a pipeline of novel drug candidates to address
the needs of patients with immuno-inflammatory diseases who lack
satisfactory treatment options. The company has a multi-stage
portfolio of drug candidates powered by a robust R&D engine
exploring protein kinase regulation. For additional information,
please visit www.aclaristx.com.
Cautionary Note Regarding Forward-Looking
Statements
Any statements contained in this press release that do not
describe historical facts may constitute forward-looking statements
as that term is defined in the Private Securities Litigation Reform
Act of 1995. These statements may be identified by words such as
“believe,” “expect,” “intend,” “may,” “plan,” “potential,” “will,”
and similar expressions, and are based on Aclaris’ current beliefs
and expectations. These forward-looking statements include Aclaris’
expectations regarding the timing of reporting results from its
clinical studies. These statements involve risks and uncertainties
that could cause actual results to differ materially from those
reflected in such statements. Risks and uncertainties that may
cause actual results to differ materially include uncertainties
inherent in the conduct of clinical trials, Aclaris’ reliance on
third parties over which it may not always have full control,
Aclaris’ ability to enter into strategic partnerships on
commercially reasonable terms, the uncertainty regarding the
macroeconomic environment and the COVID-19 pandemic and other risks
and uncertainties that are described in the Risk Factors section of
Aclaris’ Annual Report on Form 10-K for the year ended December 31,
2022 and other filings Aclaris makes with the U.S. Securities and
Exchange Commission from time to time. These documents are
available under the “SEC Filings” page of the “Investors” section
of Aclaris’ website at www.aclaristx.com. Any forward-looking
statements speak only as of the date of this press release and are
based on information available to Aclaris as of the date of this
release, and Aclaris assumes no obligation to, and does not intend
to, update any forward-looking statements, whether as a result of
new information, future events or otherwise.
Aclaris Therapeutics Contact:
Robert A. Doody Jr.Vice President, Investor
Relations484-639-7235rdoody@aclaristx.com
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