Crinetics Pharmaceuticals, Inc. has announced positive initial findings from the development program of its second clinical product candidate, atumelnant (CRN04894), at the Endocrine Society’s annual meeting (Endo2024). The results include initial data from the phase 1b/2a, open-label study in participants with acth-dependent Cushing’s syndrome (ADCS) and the phase 2 open-label Toucahn study in participants with congenital adrenal hyperplasia (CAH).
In the phase 2 Toucahn study, participants with classic CAH were treated with once-daily, oral atumelnant and assessed for safety and efficacy. The available data for the 80 mg once daily cohort showed significant reductions in key adrenal steroids associated with CAH. Specifically, 100% of participants had androstenedione (A4) levels below the upper limit of normal at two weeks with atumelnant, which was sustained through 12 weeks. The reductions in A4 and 17-hydroxyprogesterone (17-OHP) from the baseline mean were substantial, ranging from 91% to 96% for A4 and 94% to 97% for 17-OHP.
Furthermore, in the phase 1b/2a study for ADCS, initial data from five participants completing 10 days of once-daily oral atumelnant treatment (80 mg) showed rapid and profound impact on cortisol. All participants experienced serum cortisol levels below 5 mcg/dl within 10 days of administration, and 24-hour urine free cortisol was below the upper limit of normal during the treatment period.
The most common treatment-emergent adverse events included fatigue, headache, and upper respiratory tract infection. However, adverse events were generally mild to moderate, with no severe or serious treatment emergent adverse events observed to date. Notably, no early discontinuations from the study have occurred.
The company will host an investor conference call to discuss the initial findings from these two studies.
Atumelnant, the second investigational compound by Crinetics, is the first once-daily, oral adrenocorticotropic hormone (ACTH) receptor antagonist that acts selectively at the melanocortin type 2 receptor (MC2R) on the adrenal glands. It is currently in phase 2 studies for CAH and ADCS.
The Toucahn study is an ongoing, open-label, global phase 2 study designed to evaluate the efficacy, safety, and pharmacokinetics of atumelnant when administered up to 12 weeks in participants with CAH caused by 21-hydroxylase deficiency.
The results demonstrate the significant potential of atumelnant in treating both CAH and ADCS, with rapid and sustained reductions in key adrenal steroids and cortisol levels, respectively. These findings mark a significant advancement in the development of treatments for these conditions. As a result of these announcements, the company's shares have moved 3.7% on the market, and are now trading at a price of $47.99. For more information, read the company's full 8-K submission here.
