Crinecerfont Reduces Daily Steroid Dose in Adults With Congenital Adrenal Hyperplasia

A phase 3 study evaluating crinecrefont in adults with classic congenital adrenal hyperplasia due to 21-OHD met its primary and key secondary endpoints.

A phase 3 study evaluating the efficacy and safety of crinecerfont in adults with classic congenital adrenal hyperplasia (CAH) met its primary and key secondary endpoints.

In 95% of cases, patients with CAH have a mutation that causes severe deficiency of the 21-hydroxylase (21-OHD) enzyme. This results in the inability of the adrenal glands to produce cortisol, and in a majority of cases, aldosterone. Crinecerfont an oral, selective corticotropin-releasing factor type 1 receptor antagonist, is expected to decrease the production of adrenal androgens and potentially improve the symptoms of classic CAH, allowing for lower doses of glucocorticoids, the current standard of care.

The CAHtalyst study ( Identifier: NCT04490915) included 182 adult patients with CAH due to 21-OHD who were on a stable regimen of steroidal treatment. Study participants were randomly assigned to receive either crinecerfont or placebo orally twice daily for 24 weeks, followed by active treatment with crinecerfont for at least 1 year.

Findings showed a statistically significant reduction in daily glucocorticoid dose at week 24 (primary endpoint) in patients treated with crinecerfont compared with placebo (P <.0001). Crinecerfont treatment also resulted in a statistically significant decrease in androstenedione at week 4 vs placebo (P <.0001). Moreover, a greater percentage of patients treated with crinecerfont achieved a glucocorticoid daily dose to physiologic levels at week 24 (~63% vs 18% for placebo; P <.0001). The most common adverse events reported during the trial were fatigue, headache, and coronavirus infection.

“For physicians, the current treatment paradigm is problematic, relying on glucocorticoids for a dual purpose: not only to address the underlying cortisol deficiency but typically at supraphysiologic doses to treat androgen excess resulting in well-known complications over the long-term,” said Eiry Roberts, MD, Chief Medical Officer at Neurocrine Biosciences. “The CAHtalyst phase 3 adult data bring us one step closer to a new approach to treating CAH with a therapy that has demonstrated the ability to substantially reduce glucocorticoid doses while maintaining or improving androgen control.”

Additional information from the CAHtalyst adult trial will be presented at a future medical meeting. Data from the phase 3 CAHtalyst pediatric study ( Identifier: NCT04806451) are expected in the fourth quarter 2023.

This article originally appeared on MPR


Neurocrine Biosciences announces positive top-line data from phase 3 study of crinecerfont in adults for the treatment of congenital adrenal hyperplasia (CAH). News release. Neurocrine Biosciences. September 12, 2023.