Neurocrine Achieves Milestone as Congenital Adrenal Hyperplasia Candidate Triumphs in Phase III Trial

Neurocrine’s Breakthrough: Hope on the Horizon for Congenital Adrenal Hyperplasia as Phase III Trial Succeeds

In a significant stride forward, Neurocrine Biosciences has unveiled the successful results of its Phase III CAHtalyst Adult Study, signaling newfound hope for patients battling classic congenital adrenal hyperplasia (CAH). This groundbreaking trial centered around the investigational oral CRF1 antagonist, crinecerfont, has achieved its primary efficacy endpoint, marking a pivotal moment in the quest for CAH treatment.

While specific data was not disclosed in the announcement, Neurocrine’s revelation was clear: after 24 weeks of treatment with crinecerfont, patients experienced a noteworthy reduction in daily glucocorticoid dosage compared to those on a placebo. Crucially, crinecerfont maintained control over androgen levels, a critical aspect of CAH management.

Crinecerfont went on to meet key secondary endpoints by significantly lowering androstenedione levels within four weeks of treatment, a remarkable feat compared to the placebo group. Moreover, at the 24-week mark, approximately 63% of patients treated with crinecerfont saw a reduction in physiologic glucocorticoid doses, as opposed to just 18% in the placebo cohort.

These compelling findings will serve as the foundation for Neurocrine’s forthcoming regulatory applications to the FDA, with plans to submit in 2024. CEO Kevin Gorman also expressed the company’s intention to seek approval from the European Medicines Agency.

Congenital adrenal hyperplasia (CAH) encompasses a range of genetic conditions resulting from mutations that disrupt the production of adrenal hormones. Most CAH cases involve deficiencies in the 21-hydroxylase (21-OHD) enzyme, leading to cortisol and aldosterone deficits. Left untreated, CAH can lead to life-threatening complications, including salt wasting and dehydration.

The current standard of care for CAH involves glucocorticoid therapies administered at supraphysiologic doses, which can lead to severe long-term complications such as diabetes, cardiovascular disease, and osteoporosis, while also impacting patients’ cognitive function. Currently, there are no approved non-glucocorticoid treatments for CAH.

Crinecerfont, an orally available selective antagonist of the corticotropin-releasing factor type 1 receptor, offers a potential breakthrough. By blocking CRF1 receptors, it reduces the production of adrenal hormones, addressing hallmark CAH symptoms.

Neurocrine’s CAHtalyst study, featuring 182 adult patients, validated the safety and efficacy of crinecerfont’s unique mechanism of action. The study consists of a 24-week randomized, double-blinded, placebo-controlled phase, followed by a year-long open-label period, which is ongoing.

Excitingly, Neurocrine is also developing crinecerfont for pediatric patients, with Phase III enrollment completion in February 2023. Anticipated topline data from this trial are expected to emerge in the fourth quarter of this year, marking another significant step forward in the battle against CAH.

Leave a Comment