Aclaris Therapeutics Announces Top-line Results from 4-Week Phase 2b Trial of ATI-1777 for Mild to Severe Atopic Dermatitis
January 10 2024 - 7:00AM
Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage
biopharmaceutical company focused on developing novel drug
candidates for immuno-inflammatory diseases, today announced
top-line results from its Phase 2b study of ATI-1777, an
investigational topical “soft” JAK 1/3 inhibitor, in patients with
mild to severe atopic dermatitis (AD) (ATI-1777-AD-202;
NCT05432596). ATI-1777 was generated from Aclaris’ proprietary
KINect® drug discovery platform.
ATI-1777-AD-202 was a Phase 2b, multicenter, randomized,
double-blind, vehicle-controlled, parallel-group clinical trial to
evaluate the efficacy, safety, tolerability and pharmacokinetics
(PK) of multiple concentrations (0.5%, 1% and 2%) of twice daily
treatment with ATI-1777 and a single concentration (2%) of once
daily treatment with ATI-1777. For this trial, ATI-1777 was
developed as an emollient-containing spray formulation. The trial
randomized 250 patients with mild, moderate or severe AD, including
adults and children as young as 12 years old, across 30 clinical
trial sites in the United States.
“The trial demonstrated efficacy results, a pharmacokinetic
profile and safety results that were consistent with what was seen
in the Phase 2a trial of ATI-1777,” stated Dr. Neal Walker,
Aclaris’ Chairman of the Board of Directors. “We are excited that
ATI-1777 demonstrated response rates on par with existing market
competition, along with a differentiated safety profile relative to
JAK inhibitors given the low systemic absorption seen in both Phase
2 studies. These results are particularly encouraging given the
higher than anticipated vehicle response and the mid-study
inclusion of a milder patient population. The convenience of a
spray formulation along with the potential to move to once-a-day
dosing, potentially offer additional distinct advantages to
patients suffering from atopic dermatitis.”
ResultsThe trial met the primary efficacy
endpoint, the percent change from baseline in the Eczema Area and
Severity Index (EASI) score at week 4, with statistical
significance for patients treated with ATI-1777 2% BID compared to
patients treated with vehicle (69.7% versus 58.7% in the pooled
vehicle group, p=0.035). In addition, the following results were
observed with respect to the primary endpoint:
- While not statistically superior, ATI-1777 2% QD showed a trend
toward significance (68.3% compared to 59.5% in vehicle,
p=0.086).
- In the per-protocol population, or all patients who had week 4
data with no major protocol deviations, ATI-1777 2% BID
demonstrated a 70.8% reduction in EASI compared to a 58.5%
reduction in vehicle (p=0.025), and ATI-1777 2% QD demonstrated a
68.4% reduction in EASI compared to a 59.7% reduction in vehicle
(p=0.102).
- In addition, a post-hoc analysis of only patients who had
baseline severity of moderate or severe AD showed a 65.6% and 65.1%
reduction in the EASI score at week 4 in ATI-1777 2% BID and
ATI-1777 2% QD, respectively, compared to a 52.6% reduction in the
pooled vehicle group (p=0.029 and 0.040, respectively).
While not statistically powered, ATI-1777 2% BID and 2% QD also
showed improvement in the proportion of patients who reached an
IGA-TS response (Investigator Global Assessment Treatment Success,
the U.S. FDA regulatory endpoint) at week 4 (ATI-1777 2% BID: 37.2%
compared to 27.1% in vehicle, p=0.141; ATI-1777 2% QD: 36.6%
compared to 26.3% in vehicle, p=0.137). The per-protocol population
demonstrated an IGA-TS response at week 4 of 41.8% for ATI-1777 2%
BID compared to 25.5% in vehicle (p=0.059) and 39.8% for ATI-1777
2% QD compared to 25.4% in vehicle (p=0.079).
A PK analysis showed minimal levels of exposure to ATI-1777. The
mean steady state trough drug levels at week 4 were 0.319 ng/mL,
representing 0.7% of IC50 for JAK 1/3 inhibition in whole blood. In
total, 97% of ATI-1777 plasma samples from dosed patients had
concentrations below 1/10th of the IC50, and six samples (from five
ATI-1777-treated patients) of 570 samples analyzed had
concentrations above 1/4 of the IC50.
No meaningful safety findings were observed and ATI-1777 was
well tolerated. In particular, no adverse events (AEs) commonly
associated with JAK inhibitors, including serious infections,
malignancies, major adverse cardiovascular events (MACE) and
thromboses, were observed in patients treated with ATI-1777. The
most common AEs in patients treated with ATI-1777 (reported in ≥2%
patients) were nasopharyngitis (ATI-1777: 2%; vehicle: 2%) and
application site itch (ATI-1777: 2.5%; vehicle: 0%). Among patients
receiving ATI-1777, there were no discontinuations due to AEs and
one serious but unrelated AE in a patient (ATI-1777 2% QD) who
completed the study. All other AEs were mild to moderate in
severity.
“We thank the investigators and patients for their participation
in the trial, and our employees for their dedication to its
execution,” stated Douglas Manion, M.D., Aclaris’ Chief Executive
Officer. “As previously announced, we intend to seek a development
and commercialization partner for this program, which could include
additional indications such as vitiligo.”
Aclaris plans to submit the full results to an upcoming
scientific conference.
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,” “anticipate,” “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 development
strategy for ATI-1777, including intentions to seek a development
and commercialization partner for the asset, and its plans to
submit the data to an upcoming scientific conference. 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 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:
investors@aclaristx.com
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