Crinetics announces ‘positive’ topline results from fourth cohort of CAH study

The TouCAHn trial is an open-label, global, Phase 2 study designed to evaluate the efficacy, safety, and pharmacokinetics of atumelnant when administered for 12 weeks in people with CAH caused by 21-hydroxylase deficiency. The fourth cohort of the study enrolled 10 patients with classic CAH on a stable dose of glucocorticoid replacement; two patients withdrew consent. The participants received atumelnant once daily in the morning and underwent glucocorticoid dose reduction toward physiologic levels in weeks 2 to 10. Primary endpoints included change from baseline in morning serum androstenedione levels and incidence of treatment-emergent adverse events. Treatment with atumelnant resulted in rapid, sustained lowering of androstenedione in all 8 patients that completed the fourth cohort. Seven out of these 8 patients continued to maintain lower A4 after glucocorticoid doses were reduced to physiologic levels. A data snapshot with limited source data verification from the first 7 patients in the Open-Label Extension to have completed 13 weeks shows both serum A4 reductions and GC dose reductions that are in line with those seen in Cohort 4. Additionally, investigators have not observed any serious adverse events or any treatment-related severe adverse events, and have not observed any hepatic transaminase adverse events to date with 25 patients enrolled and with 7 participants who have completed over 20 weeks of treatment in the study. Atumelnant continues to be well-tolerated with a growing safety database including over 750 weeks of cumulative adult CAH patient exposure. In the overall clinical program, to date, over 200 participants have been exposed to atumelnant in a combination of healthy volunteer, clinical pharmacology, Cushing’s and CAH studies and continues to demonstrate a favorable risk-benefit profile.