Neurocrine’s congenital adrenal hyperplasia candidate clears Phase III
Published: Sep 13, 2023
By Tristan Manalac
Neurocrine Biosciences’ investigational oral CRF1 antagonist crinecerfont met the primary efficacy endpoint in the Phase III CAHtalyst Adult Study in patients with classic congenital adrenal hyperplasia, according to topline results announced Tuesday.
The California-based biopharma company did not provide specific data in its news release but said that at 24 weeks crinecerfont treatment induced a significant decrease in daily glucocorticoid dose, as compared with placebo. The candidate was also able to maintain androgen control.
Crinecerfont likewise met key secondary endpoints, significantly reducing androstenedione levels after four weeks of treatment, as compared with placebo. In addition, at week 24, physiologic glucocorticoid doses were lowered in approximately 63% of crinecerfont-treated patients, as opposed to only 18% of placebo comparators.
Neurocrine will use these data—along with results from an open-label period—as the basis for its regulatory applications to the FDA, which the company hopes to submit in 2024. CEO Kevin Gorman said the company will also file for approval with the European Medicines Agency.
Congenital adrenal hyperplasia (CAH) is a group of genetic conditions arising from mutations that lead to the deficiency of adrenal hormones. Most CAH cases involve deficiencies in the 21-hydroxylase (21-OHD) enzyme, which in turn impairs the production of cortisol and often aldosterone. Unchecked, CAH can lead to salt wasting, dehydration and death.
The gold standard for CAH treatment is glucocorticoid therapies, given at doses above physiologic levels. With prolonged treatment, these supraphysiologic doses of glucocorticoids can lead to serious complications including diabetes, cardiovascular disease and osteoporosis, as well as compromise patients’ cognition. There are currently no non-glucocorticoid treatments approved for CAH.
Crinecerfont is an orally available selective antagonist of the corticotropin-releasing factor type 1 receptor. By blocking CRF1 receptors, crinecerfont reduces the overall levels of adenocorticotropic hormone, which leads to the suppression of the production of adrenal hormones and, in turn, addresses typical symptoms of classic CAH.
Neurocrine tested the safety and efficacy of this mechanism of action in CAHtalyst, a registrational study with 182 adult patients enrolled. The study consists of a 24-week randomized, placebo-controlled and double-blinded part, followed by a one-year open label portion, which is currently ongoing.
The company is also developing crinecerfont for children. A Phase III study completed enrollment in February 2023. Neurocrine is anticipating topline and potentially registrational data from this trial in the fourth quarter of this year.