WAYNE, PA — Aclaris Therapeutics, Inc. (NASDAQ: ACRS) this week 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).
The 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.
Zunsemetinib 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.
PK 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.”
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