Aclaris claims win for ‘soft’ JAK inhibitor but mixed data spooks investors

Aclaris Therapeutics has touted the latest phase 2 results for its “soft” JAK 1/3 inhibitor as a win for the beleaguered biotech, but investors appeared less enthusiastic about the wider set of mixed data.

The phase 2b study involved 250 adults and children in the U.S. with mild to severe atopic dermatitis receiving either twice daily treatment with the therapy, called ATI-1777, as a spray at concentrations of 0.5%, 1% or 2%, or a once daily treatment of 2% or vehicle.

At week four, the change in eczema from baseline as assessed by the Eczema Area and Severity Index (EASI) score was 69.7% for patients who received the 2% concentration twice daily compared with 58.7% for those who received the vehicle. The statistical significance of this difference, which equated to a p value of 0.035, met the trial’s primary efficacy endpoint, Aclaris said in a Jan. 10 release.

However, while patients who received the once daily 2% concentration also saw a “trend toward significance”—with a 68.3% change compared to 59.5% among those receiving a vehicle—this was not “statistically superior,” the biotech admitted.

Investors appeared dubious about the readout, sending Aclaris’ shares down 14% to $1.10 in pre-market trading from a Tuesday closing price of $1.28.

While the trial had not been statistically powered for a response as measured by the Investigator Global Assessment Treatment Success, which the company noted is the FDA’s regulatory endpoint, Aclaris said the drug had shown improvement here as well, with changes of 37.2% and 36.6% for the once daily and twice daily 2% concentrations, respectively, compared to 27.1% and 26.3% in the respective vehicle cohorts.

Aclaris did not share data on the efficacy of the 0.5% and 1% concentrations in the release.

ATI-1777 had not produced any of the adverse events most commonly associated with JAK inhibitors, such as serious infections, malignancies, major adverse cardiovascular events or thromboses, according to the company. The most common adverse events among treated patients were nasopharyngitis and application site itch.

“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,” Neal Walker, chairman of Aclaris’ board of directors, said in the release.

“These results are particularly encouraging given the higher than anticipated vehicle response and the mid-study inclusion of a milder patient population,” Walker added. “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.”

Aclaris had been pinning its hopes on ATI-1777’s success after the company announced in the final weeks of the year that it was laying off almost half of its workforce as it resurrected plans to explore its MK2 inhibitor zunsemetinib despite a couple of mid-phase fails.

At the time, Aclaris said that it would use a positive set of phase 2 data for ATI-1777 to hunt for a suitable partner for the asset.” In this morning’s release, the biotech’s CEO Douglas Manion, M.D., confirmed that the company would now “seek a development and commercialization partner for this program, which could include additional indications such as vitiligo.”