Aclaris Therapeutics Announces Top-line Results from 4-Week Phase 2b Trial of ATI-1777 for Mild to Severe Atopic Dermatitis

Rhea-AI Summary

Aclaris Therapeutics, Inc. (NASDAQ: ACRS) announced top-line results from its Phase 2b study of ATI-1777, an investigational topical 'soft' JAK 1/3 inhibitor, in patients with atopic dermatitis. The trial achieved a statistically significant result in the primary efficacy endpoint at week 4, demonstrating response rates on par with existing market competition and a differentiated safety profile. The trial met the primary efficacy endpoint, showing a significant reduction in the Eczema Area and Severity Index (EASI) score at week 4 for patients treated with ATI-1777 2% BID compared to patients treated with the vehicle. A PK analysis showed minimal levels of exposure to ATI-1777, and it was well tolerated with no serious adverse events commonly associated with JAK inhibitors.

Medical Research Analyst

The Phase 2b study results for ATI-1777, a topical JAK 1/3 inhibitor, indicate a significant milestone in the treatment of atopic dermatitis (AD), a chronic skin condition with a high prevalence rate. The reported efficacy of ATI-1777 in reducing the Eczema Area and Severity Index (EASI) score, particularly the 2% BID concentration, suggests a competitive potential against existing treatments in the market. The minimal systemic exposure observed is particularly noteworthy, as it may reduce the risk of side effects commonly associated with systemic JAK inhibitors, such as serious infections and malignancies.

From a medical research perspective, the differentiated safety profile and the convenience of a spray formulation could position ATI-1777 favorably among patients and healthcare providers. Furthermore, the potential once-daily dosing regimen could enhance patient adherence to treatment, a critical factor in chronic disease management. The post-hoc analysis revealing greater efficacy in patients with moderate to severe AD underscores the drug's potential in treating more severe cases, which often present a greater challenge in clinical management.

Financial Analyst

The announcement of positive Phase 2b trial results for Aclaris Therapeutics' ATI-1777 could have a favorable impact on the company's financial outlook. As a clinical-stage biopharmaceutical company, the transition of drug candidates from clinical trials to market approval is a pivotal driver of value. With the AD treatment market projected to grow, driven by increasing prevalence and demand for safer, more effective treatments, Aclaris' stock may garner increased investor attention.

Investors should note the company's intention to seek a development and commercialization partner, which could result in licensing deals or partnerships that provide upfront payments, milestone payments and royalties, potentially improving Aclaris' revenue streams and reducing commercialization risks. However, the market for AD treatments is competitive and the success of ATI-1777 will depend not only on its clinical efficacy and safety profile but also on the strategic execution of its market entry and the negotiation of partnership terms.

Market Research Analyst

The atopic dermatitis market is witnessing a surge in the development of novel therapies, with an increasing focus on targeted treatments like JAK inhibitors. ATI-1777's promising results in efficacy and safety could make it a strong contender in this space. Given the chronic nature of AD, treatments that offer a balance between efficacy and safety, with convenient administration methods, are likely to capture significant market share.

Analyzing the competitive landscape, the unique 'soft' JAK inhibitor approach of ATI-1777, which aims to limit systemic absorption, could be a distinguishing feature that sets it apart from other therapies. The potential for a once-daily treatment regimen could also enhance its marketability. The impact on the stock market will be contingent on Aclaris' ability to navigate regulatory pathways, secure a commercialization partner and effectively market the product upon approval.

- ATI-1777 2% BID Achieved a Statistically Significant Result in the Primary Efficacy Endpoint at Week 4 -

- Minimal Systemic Exposure Supports “Soft” Topical JAK Inhibitor Approach -

- ATI-1777 Was Well Tolerated -

WAYNE, Pa., Jan. 10, 2024 (GLOBE NEWSWIRE) -- 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.”

Results
The 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

FAQ

What is the latest update on Aclaris Therapeutics, Inc. (ACRS)?

Aclaris Therapeutics, Inc. (ACRS) announced top-line results from its Phase 2b study of ATI-1777, an investigational topical 'soft' JAK 1/3 inhibitor, in patients with atopic dermatitis.

What were the results of the Phase 2b study of ATI-1777 by Aclaris Therapeutics, Inc. (ACRS)?

The trial achieved a statistically significant result in the primary efficacy endpoint at week 4, demonstrating response rates on par with existing market competition and a differentiated safety profile.

What is the primary efficacy endpoint of the Phase 2b study of ATI-1777 by Aclaris Therapeutics, Inc. (ACRS)?

The primary efficacy endpoint was the percent change from baseline in the Eczema Area and Severity Index (EASI) score at week 4.

What were the key safety findings of the Phase 2b study of ATI-1777 by Aclaris Therapeutics, Inc. (ACRS)?

A PK analysis showed minimal levels of exposure to ATI-1777, and it was well tolerated with no serious adverse events commonly associated with JAK inhibitors.