Neurocrine Biosciences Presented CAHtalyst™ Phase 3 Studies and CAHtalog™ Data at ENDO 2024

Neurocrine Biosciences, Inc. and its subsidiary Diurnal Ltd. recently presented significant findings at the Endocrine Society Annual Meeting, ENDO 2024. They showcased data from their neuroendocrinology pipeline, including the primary results from their CAHtalyst™ Phase 3 registrational studies on crinecerfont for treating congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency in both pediatric and adult patients. Additionally, they introduced CAHtalog™ Registry data, which highlights the adverse effects of high glucocorticoid (GC) doses and the natural progression of the disease in CAH patients.

Chief Medical Officer at Neurocrine Biosciences, Dr. Eiry W. Roberts, expressed excitement about sharing the recently published CAHtalyst Phase 3 data with ENDO 2024 attendees, noting that crinecerfont presents a promising new treatment approach for managing CAH. The CAHtalyst studies indicated crinecerfont's potential to reduce elevated androgen levels and lower excessive GC doses while maintaining androgen control in patients aged four years and older.

CAHtalyst™ Phase 3 Data Highlights

- Adult Study: Dr. Richard Auchus from the University of Michigan presented data showing the study met its primary and secondary endpoints. Among crinecerfont-treated adults, 63% achieved a reduction in GC dosing to physiological levels (≤ 11mg/m^2/day) while maintaining androstenedione control at Week 24, compared to just 18% in the placebo group. This data was published in The New England Journal of Medicine.

- Pediatric Study: Dr. Kyriakie Sarafoglou from the University of Minnesota presented pediatric data indicating the study met its primary and key secondary endpoints and was well-tolerated. 29.9% of crinecerfont-treated children achieved a reduction in GC dosing to physiological levels at Week 28 while maintaining androgen control, compared to 0% in the placebo group. This data was also published in The New England Journal of Medicine.

CAHtalog™ Registry Findings

The CAHtalog registry examined the impact of high GC doses in pediatric and adult CAH patients, revealing several key findings:

- Among 44 pediatric patients, 27.3% received high GC doses (>15 mg/m^2/day). This was linked to premature adiposity rebound, early growth acceleration followed by reduced pubertal growth.
- In 69 patients (45 pediatric, 34 adult), higher GC doses were associated with increased prevalence of hypertensive diseases and metabolic complications. Short stature was more common among pediatric patients on high GC doses.
- In 40 patients with multiple GC-androstenedione records, 92% experienced health state transitions over a median 7-year period. Only 3% maintained a stable health state with normal GC and androstenedione levels throughout.

Natural History of CAH

A longitudinal study from the CAHtalog registry provided insights into the natural history of classic CAH, showing that:

- Pediatric patients exhibited early growth acceleration followed by stunted pubertal growth, particularly in females.
- Mean bone age-to-chronological age ratios peaked at age 5 in females and age 7 in males.
- Body Mass Index (BMI) trends indicated early obesity, which often persisted into adulthood. Obesity, hypertension, and metabolic comorbidities were common, especially in adults.

Claims-Based Cohort Analysis

A retrospective study using insurance claims data from 2020-2022 showed higher rates of chronic conditions related to adrenal androgen excess and supraphysiologic GC dosing in CAH patients compared to the general population. Notable comorbidities included anxiety disorders, obesity, fatigue, depression, and excess hair growth in females.

Conclusion

The comprehensive data presented underscores the significant clinical burden of current CAH treatments, which often require supraphysiologic GC doses leading to numerous health complications. The findings highlight the potential of crinecerfont to offer a new treatment paradigm that could mitigate these challenges. The CAHtalog registry continues to provide valuable real-world insights into the management of CAH, emphasizing the need for optimized disease management strategies.

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