Neurocrine Biosciences Shares CAHtalyst™ and Hydrocortisone Study Data at ECE 2024

Neurocrine Biosciences, Inc. and Diurnal Ltd., a subsidiary, recently unveiled significant data from several clinical studies at the European Congress of Endocrinology 2024 in Stockholm. These studies highlight the limitations of current treatments for congenital adrenal hyperplasia (CAH) and primary adrenal insufficiency and propose new avenues for potentially more effective therapies.

The CAHtalyst™ Phase 3 studies focused on crinecerfont's efficacy in treating both pediatric and adult patients with CAH. The pediatric study enrolled 103 participants aged 4 to 17 years, primarily in Tanner stages 3-5, with a majority showing signs of inadequate adrenal androgen control despite high doses of glucocorticoids. Common complications included advanced bone age, early puberty, obesity, hirsutism in females, and testicular adrenal rest tumors in males.

Similarly, the adult study involved 182 participants with CAH, revealing elevated levels of adrenocorticotropic hormone, 17-hydroxyprogesterone, and androstenedione despite supraphysiologic glucocorticoid doses. Many exhibited comorbidities like anxiety, osteopenia, depression, hypertension, and hyperlipidemia. Almost half of the participants were overweight, and notable percentages reported hirsutism and acne in females, and testicular adrenal rest tumors in males.

Eiry W. Roberts, M.D., Chief Medical Officer at Neurocrine Biosciences, underscored the concerning trend of elevated adrenal androgens and other steroid markers in both pediatric and adult patients. This situation calls for new glucocorticoid-independent treatments.

In 2023, Neurocrine Biosciences announced promising top-line results from these studies, leading to New Drug Application submissions to the U.S. Food and Drug Administration in April 2024.

Another significant study presented was the Phase 2 CHAMPAIN trial, which examined the effects of modified-release hydrocortisone (Chronocort®) in adults with primary adrenal insufficiency. This study demonstrated that participants achieved physiological morning cortisol levels after four weeks of treatment with Chronocort® compared to once-daily Plenadren. The results showed a significant improvement in morning cortisol levels with Chronocort®, indicating its potential to better manage this condition.

The Phase 3 extension study of Chronocort® in CAH patients also yielded encouraging results. Participants showed a reduction in the median daily hydrocortisone dose from 30mg to 20mg, and a greater number achieved target hormone levels on lower doses of hydrocortisone. This suggests that Chronocort® not only improves biochemical control but also reduces the required glucocorticoid dose, potentially minimizing the side effects associated with higher doses.

Crinecerfont, developed for treating CAH due to 21-hydroxylase deficiency, works by antagonizing corticotropin-releasing factor type 1 receptors to reduce excess adrenal androgens. This mechanism allows for lower, more physiological glucocorticoid dosing, aiming to alleviate the complications associated with current treatments.

Both the pediatric and adult CAHtalyst™ Phase 3 studies have completed their primary phases, with ongoing open-label treatment portions. The studies aim to evaluate crinecerfont's safety, efficacy, and tolerability in patients with CAH.

Primary adrenal insufficiency, characterized by insufficient production of adrenal hormones like cortisol and aldosterone, is currently managed with glucocorticoids which often do not match the body’s natural rhythm. Diurnal Ltd.'s modified-release hydrocortisone, designed to mimic the natural circadian rhythm, has shown promising results in both primary adrenal insufficiency and CAH.

Neurocrine Biosciences, a leading biopharmaceutical company, continues to focus on innovative treatments for complex conditions, applying its expertise in neuroscience and endocrinology to develop therapies that significantly improve patient outcomes.