Safety and statistical significance

WAYNE, Pa.—The completion of a Phase 2 clinical trial brought with it good news for Aclaris Therapeutics Inc., which reported a strong response in its AUAT-201 Oral trial of ATI-501. The trial sought to evaluate ATI-501, an investigational oral Janus kinase (JAK) 1/3 inhibitor, in patients with alopecia areata.

 

Alopecia areata is an autoimmune condition in which patients experience patchy, non-scarring hair loss on the body and scalp. In more severe forms, patients can face total scalp hair loss, known as alopecia totalis, or total hair loss on the scalp and body, which is known as alopecia universalis. Approximately 1.8 percent of the U.S. population is affected by this condition, with roughly 2 percent affected globally. Onset can occur in childhood, though most people present with alopecia areata by the age of 40, and many individuals with this condition experience issues such as anxiety, depression or diminished quality of life.

 

AUAT-201 Oral was a Phase 2 randomized, double-blinded, parallel-group, placebo-controlled trial, meant to assess the safety, efficacy and dose response of three doses of ATI-501 on the regrowth of hair in 87 subjects with alopecia areata, including patchy alopecia, alopecia totalis and alopecia universalis. Participants all had between 30 percent to 100 percent total scalp hair loss, and were randomized in a 1:1:1:1 ratio and received 24 weeks of treatment, twice daily, of either 400 mg, 600 mg or 800 mg of ATI-501 or a placebo oral suspension.

 

The primary endpoint for this trial was the mean percent change from baseline patients’ Severity of Alopecia Tool (SALT) scores at week 24. Secondary endpoints included absolute change in SALT scores from baseline, Alopecia Density and Extent (ALODEX) percent change from baseline, and ALODEX absolute change from baseline. Statistically significant improvements were seen in the primary and secondary endpoints.

 

“We are pleased with these results, and we thank the patients and the investigators who participated in this trial,” said Dr. David Gordon, chief medical officer of Aclaris.

 

“All three active groups were significantly better than placebo for the change from baseline in SALT scores,” Gordon reported in a conference call regarding the AUAT-201 data. “The reductions were 6 percent in the placebo group vs. 26 percent, 30 percent and 26 percent in the 400, 600 and 800 mg groups, respectively. These changes were highly statistically significant … The change in ALODEX showed a similar trend. The placebo group had an 8-percent reduction, and the 400, 600 and 800 mg groups dropped by 27 percent, 32 percent and 27 percent, respectively—all highly statistically significant.”

 

ATI-501 proved to be generally well tolerated at all doses, with no serious adverse events. Two subjects each in the placebo group and the 400 mg group discontinued the study due to adverse events, as did one subject in the 600 mg group. The most common adverse events were nasopharyngitis, influenza, upper respiratory tract infection, urinary tract infection, acne, blood creatine phosphokinase increased and sinusitis.

 

“Although we have made a lot of progress in understanding this disease, there is still much to learn in terms of length of treatment, durability effect and the optimal target product profile,” Dr. Neal Walker, president and CEO of Aclaris, remarked in the company's conference call.

 

In an update on Aclaris’ business strategy, released on August 8, the company announced that it plans to enlist a strategic partner for the development and commercialization of ATI-501 and ATI-502 in alopecia. This was followed on Sept. 5 with the news that after completing a strategic review of the company, Aclaris had decided to focus its efforts on its immuno-inflammatory development programs and seeking out commercialization partners for its commercial products.

 

“We believe this change in strategy will benefit Aclaris in the near term by lowering expenses and eliminating the inherent risks and investment related to maintaining a commercial infrastructure. By actively seeking a commercialization partner for our commercial products business and refocusing our resources with a view to optimizing our immuno-inflammatory development portfolio, we believe we can significantly reduce our costs, strengthen the organization, and extend our cash runway,” Walker stated. “Our resources can now be dedicated to prudently advancing our pipeline of novel drug candidates for immuno-inflammatory diseases.”