Neurocrine Biosciences Publishes Phase 3 Study Results of Crinecerfont for CAH in NEJM

Neurocrine Biosciences has announced successful results from its CAHtalyst™ Phase 3 study, demonstrating the efficacy of crinecerfont in treating adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The primary and key secondary endpoints of the study were met, indicating a significant reduction in glucocorticoid (GC) doses while maintaining control of androgen levels.

The study, involving 182 participants, showed that crinecerfont treatment led to a markedly greater GC dose reduction at Week 24 compared to placebo. Specifically, participants receiving crinecerfont exhibited a -27.3% reduction in GC dose from baseline, while the placebo group showed only a -10.3% reduction. Furthermore, 62.7% of crinecerfont-treated participants achieved physiologic GC dosing while maintaining androstenedione control, compared to just 17.5% in the placebo group.

Crinecerfont works by antagonizing corticotropin-releasing factor type 1 receptors, thereby reducing adrenocorticotropic hormone (ACTH) and adrenal androgen levels independently of GC. The study's results suggest that this mechanism can effectively lower GC doses to more physiologic levels, potentially mitigating the adverse effects associated with long-term supraphysiologic GC therapy, such as osteoporosis, obesity, and insulin resistance.

The findings were published in The New England Journal of Medicine and presented at the ENDO 2024 conference by Dr. Richard Auchus, highlighting the significant clinical implications of crinecerfont as a potential new treatment paradigm for CAH patients. The data support the idea that crinecerfont can help manage CAH more effectively, reducing the health risks linked to high-dose GC therapy while maintaining androgen control.

In terms of safety, crinecerfont was generally well-tolerated. The most common adverse events were fatigue and headache, with few serious adverse events occurring, none of which were attributed to the drug. Additionally, there was no significant concern related to adrenal crisis, as the incidence of related adverse events was similar between the crinecerfont and placebo groups.

The CAHtalyst Adult Phase 3 study not only met its primary and key secondary endpoints but also revealed favorable trends in parameters associated with long-term GC therapy. These included improvements in body weight, insulin resistance, and glucose tolerance, as well as increased bone resorption and formation markers, indicating a potential reversal of GC-induced bone turnover suppression.

Crinecerfont's ability to decrease androstenedione levels through a GC-independent mechanism was confirmed, as evidenced by a significant reduction in androstenedione levels at Week 4 and maintained reductions at Week 24 in crinecerfont-treated participants. In contrast, placebo participants experienced an increase in androstenedione levels when GC doses were reduced.

Neurocrine Biosciences is advancing the development of crinecerfont with ongoing open-label studies as part of the CAHtalyst™ program, targeting both pediatric and adult populations. The promising Phase 3 results have paved the way for New Drug Application submissions to the U.S. Food and Drug Administration, aiming to offer a new treatment option for patients with CAH.

Overall, crinecerfont represents a significant advancement in CAH treatment, offering the potential for improved health outcomes by enabling lower GC doses and better androgen control. The study's success underscores the importance of innovative therapeutic strategies in managing complex endocrine disorders.