Sagimet Biosciences Eyes U.S. Phase III Acne Study After Positive China Data

Sagimet Biosciences plans to begin a Phase III study of its oral fatty acid synthase, or FASN, inhibitor denifanstat in moderate-to-severe acne within the next several months, following positive results from a China-based Phase III trial conducted by partner Ascletis, company executives said during a Canaccord Genuity discussion. Chief Executive Officer David Happel said Sagimet is a clinical-stage biopharmaceutical company focused on conditions associated with overexpression or overactivity of FASN. The company’s programs include acne, liver disease and certain tumors that depend on FASN for disease progression. Denifanstat is designed to address de novo lipogenesis, or fat accumulation, Happel said. In acne, the process contributes to excess sebum production, inflammation, bacterial load and hyperkeratinization, or plugging of the skin. He said denifanstat directly targets sebum and inflammation, the two primary drivers the company is pursuing in acne treatment. Ascletis’ Phase III trial in China enrolled 480 patients with moderate-to-severe acne, randomized one-to-one between active treatment and placebo. Patients had investigator global assessment, or IGA, scores of 3 to 4 and substantial inflammatory and non-inflammatory lesion counts at baseline. The trial met its two primary endpoints, according to Grauer, showing statistically significant results for IGA success and reduction in inflammatory lesions. It also showed significant reductions in non-inflammatory lesions. He said IGA success improved by about 20 percentage points over placebo. The safety profile was positive. Dry eye was reported in a little more than 10% of treated patients, compared with 9% of placebo patients, while dry skin was reported in approximately 6% of treated patients versus 2% on placebo. No Grade 3 or serious adverse events were observed in the study. Sagimet’s planned U.S. Phase III study will enroll 800 patients with moderate-to-severe acne, including 450 adolescents ages 12 to 17. The study will use a 2:1 randomization, intended to provide at least 300 adolescents receiving the drug, as requested by the Food and Drug Administration. The primary analysis will occur at 12 weeks and will assess three endpoints: success on the Evaluator’s Global Severity Score, or EGSS, inflammatory lesion reduction and non-inflammatory lesion reduction. The patient population and overall design will be similar to the Ascletis study. The company has an open investigational new drug application and has received a “study may proceed” determination from the FDA. Sagimet expects to dose its first patient within the next couple of months, with last-patient, last-dose anticipated around this time next year and topline data shortly afterward.