Article highlights
- Crinecerfont, an investigational oral treatment, shows promise in controlling adrenal androgens in children and adolescents with classic congenital adrenal hyperplasia (CAH).
- In a phase 3 study with 103 participants aged 2 to 17, crinecerfont significantly reduced serum androstenedione levels compared to placebo.
- Patients treated with crinecerfont were able to decrease their daily glucocorticoid dose while maintaining androgen control, a significant achievement in CAH management.
- The innovative approach of crinecerfont offers a potential solution for managing CAH without relying on traditional glucocorticoid treatments.
- These findings mark a significant step in shifting the treatment paradigm for CAH and improving clinical outcomes related to androgen excess.
Crinecerfont (Neurocrine Biosciences) has demonstrated positive phase 3 data to treat children and adolescents with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, according to a press release from Neurocrin Biosciences.
Crinecerfont, an investigational, oral, selective corticotropin-releasing factory type 1 receptor antagonist, achieved the primary and key secondary endpoints in the phase 3 CAHtalyst Pediatric Study (NCT04806451), which evaluated efficacy, safety, and tolerability. The treatment is being developed to help control and reduce excess adrenal androgens via a steroid-independent mechanism, according to the manufacturer.
CAH refers to a group of genetic conditions that can lead to an enzyme deficiency which can change the production of adrenal hormones that are essential for life. Of all CAH cases, approximately 95% are because of a mutation that leads to an enzyme 21-hydroxylase (21-OHD) deficiency. Severe deficiency of this enzyme in classic CAH can lead to the inability of the adrenal glands to produce cortisol, and in about 75% of cases, aldosterone.
The phase 3 pediatric study featured 103 male and female children and adolescents aged 2 to 17 years. The 28-week, randomized, double-blind, placebo-controlled study began in July 2021. The primary outcome was a statistically significant decrease in serum androstenedione from baseline at week 4 compared to placebo, following a glucocorticoid (GC) stable period, which crinecerfont achieved (P = .0002). Consistent with the Phase 3 CAHtalyst Adult Study (NCT04490915), patients treated with crinecerfont had a statistically significant reduction from baseline in daily GC dose, while maintaining androgen control at 28 weeks compared to placebo (P < .0001).
Of crinecerfont-treated patients, approximately 30% achieved a reduction to a physiologic GC dose while keeping androgen control, compared to 0% in placebo-treated patients. A statistically significant decrease in serum 17-hydroxyprogesterone from baseline at week 4, another key secondary outcome, was also observed compared to placebo (P < .0001). Twenty-four weeks of open-label crinecerfont treatment and optional open-label extension followed the study. This portion is still ongoing.
