Crinetics Pharma Reports Positive Phase 2 Results for Atumelnant Trial

Crinetics Pharmaceuticals, Inc., a clinical stage pharmaceutical company, announced positive topline results from an open-label, phase 2 congenital adrenal hyperplasia (CAH) study of investigational atumelnant, a novel, once-daily oral adrenocorticotropic hormone (ACTH) receptor antagonist candidate being developed for the treatment of classic CAH and ACTH-dependent Cushing’s syndrome.

“These exciting results show atumelnant not only lowered key biomarkers, but also had a significant impact on the signs and symptoms of CAH that are important to the overall health of people living with this condition,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “We are eager to move forward with a global phase 3 pivotal trial for adults in CAH, as we simultaneously prepare to start a phase 2b/3 trial in paediatric patients this year. Our internally discovered pipeline now has two drug candidates with positive late stage data, and we look forward to submitting INDs for four additional candidates now in first-in-human enabling studies, as we continue our strategy for building the premier global endocrine company.”

“There has been a long-standing interest in using a potent, selective antagonist of the ACTH receptor for the treatment of CAH and other diseases of ACTH excess, leading to the design of atumelnant by Crinetics scientists” said Dr. Alan Krasner, M.D., chief endocrinologist of Crinetics. “This phase 2 study demonstrated that atumelnant was well tolerated and resulted in a reduction of adrenal androgen levels so rapid and robust that it allowed patients to realize meaningful improvements in long-term, pre-existing medical challenges, even within the short 12-week treatment period of this 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 study enrolled 28 patients across 3 dose cohorts with classic CAH on a stable dose of glucocorticoid replacement.

Primary endpoints included change from baseline in morning serum androstenedione (A4) levels and incidence of treatment-emergent adverse events. Change from baseline in morning serum 17-hydroxyprogesterone (17-OHP) was also evaluated as a secondary endpoint.

For all doses, treatment with atumelnant resulted in rapid, substantial and sustained statistically significant reduction in A4 levels, the key biomarker for disease control.

Additionally, rapid, substantial and sustained statistically significant reductions in 17-OHP, a confirmatory secondary biomarker of disease control, were achieved across doses. Treatment with atumelnant also had a significant impact on CAH signs and symptoms, including:  Substantial reduction and normalization of testosterone in the majority of female participants (8/13),1 with 6 of the 11 impacted participants resuming menses;  Consistent reduction in total adrenal volume observed across dose cohorts; Resolution of androgen mediated polycythemia in 5 of the 6 impacted participants.

Atumelnant has been generally well tolerated with no treatment-related severe or serious adverse events to date, irrespective of disease severity or dose level. No participants required dose reduction or discontinued from the trial. All adverse events to-date have been mild to moderate and generally transient. No consistent clinically important trends were observed across key safety parameters, including clinical safety laboratory values, physical examination, electrocardiogram or vital signs. The most common treatment-emergent adverse events included headache (7/28) and fatigue (5/28).

Atumelnant, Crinetics’ second investigational compound, is the first once-daily, oral adrenocorticotropic hormone (ACTH) receptor antagonist that acts selectively at the melanocortin type 2 receptor (MC2R) on the adrenal gland. Diseases associated with excess ACTH can have significant impact on physical and mental health. Atumelnant has exhibited strong binding affinity for MC2R in preclinical models and has demonstrated suppression of adrenally derived glucocorticoids and androgens that are under the control of ACTH. Data from a 12-week phase 2 study demonstrated compelling treatment benefits of atumelnant, evidenced by the rapid, substantial and sustained statistically significant reductions in key CAH disease related biomarkers, including androstenedione and 17-hydroxyprogesterone, in a diverse population. Atumelnant is currently in development for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome.For more information about the phase 2 TouCAHn study in classic CAH, please visit clinicaltrials.gov (NCT05907291).

Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumours.

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