Crinetics Initiates Phase 3 Trial of Atumelnant for Congenital Adrenal Hyperplasia
Key Insights
Crinetics Pharmaceuticals has dosed the first patient in the CALM-CAH (search) Phase 3 trial evaluating atumelnant, a novel once-daily oral ACTH receptor (search) antagonist for classic congenital adrenal hyperplasia (search).
The Phase 3 study builds on positive Phase 2 results that demonstrated rapid and sustained reductions in key disease biomarkers including androstenedione and 17-hydroxyprogesterone.
Atumelnant is the first-and-only small molecule ACTH receptor (search) antagonist in late-stage clinical development, designed to block excess androgen production in the adrenal gland.
Crinetics Pharmaceuticals has announced the dosing of the first patient in the CALM-CAH (search) Phase 3 trial, marking a significant milestone in the development of atumelnant for classic congenital adrenal hyperplasia (search) (CAH). The randomized, placebo-controlled study represents the advancement of the first-and-only small molecule ACTH receptor (search) antagonist into late-stage clinical development for this rare endocrine disorder.
Novel Mechanism Targets Root Cause of Disease
Atumelnant is designed to block the pathway in the adrenal gland that leads to the production of excess androgens associated with classic CAH (search). The investigational drug acts selectively at the melanocortin type 2 receptor (search) (MC2R (search)) on the adrenal gland, demonstrating strong binding affinity in preclinical models and suppression of adrenally derived glucocorticoids and androgens under ACTH control.
"Through the CALM-CAH (search) study, we will evaluate atumelnant's ability to normalize adrenal androgen levels while simultaneously reducing glucocorticoid levels to the physiologically normal range," said Dana Pizzuti, M.D., Chief Medical and Development Officer of Crinetics. "With a unique endpoint measuring both of these objectives, CALM-CAH sets a new standard in terms of assessing overall disease control."
Strong Phase 2 Foundation Supports Advancement
The Phase 3 trial builds on compelling Phase 2 results from a 12-week study that demonstrated rapid, substantial and sustained statistically significant reductions in key CAH (search) disease-related biomarkers. Treatment with atumelnant was associated with reductions in androstenedione and 17-hydroxyprogesterone, as well as other clinical measures of disease activity including adrenal size and resumption of menses in a diverse patient population.
The CALM-CAH (search) Phase 3 study is designed to assess reductions in excess androgens, improvements in glucocorticoid use, and other clinical outcomes that reflect disease control in adults with classic CAH. The trial represents a registrational study that could support regulatory approval if successful.
Regulatory Recognition and Unmet Medical Need
Crinetics recently received Orphan Drug Designation from the U.S. Food & Drug Administration (FDA) for atumelnant in the treatment of classic CAH (search), recognizing both the rarity of the condition and the potential therapeutic benefit of the investigational treatment. Diseases associated with excess ACTH can have a significant impact on physical and mental health, highlighting the substantial unmet medical need in this patient population.
Broader Pipeline and Company Focus
Atumelnant is part of Crinetics' broader focus on endocrine diseases, with the company's lead product PALSONIFY (search) (paltusotine) already approved by the FDA as the first once-daily, oral treatment for adults with acromegaly (search). The company's pipeline includes over 10 disclosed programs targeting various endocrine conditions through its core expertise in G-protein coupled receptors (GPCRs) with specifically tailored small molecule pharmacology.
Beyond CAH (search), atumelnant is also in development for ACTH-dependent Cushing's syndrome (search), potentially offering transformational care for individuals living with multiple ACTH-related endocrine disorders. The advancement into Phase 3 development represents a significant step toward potentially revolutionizing the management of these conditions and providing unprecedented improvements in quality of life for affected patients.