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The FDA approved crinecerfont (Crenessity) as a first-in-class treatment for classic congenital adrenal hyperplasia (CAH), the late Friday.

Crinecerfont was approved for use in combination with glucocorticoids in patients ages 4 years and older with the rare genetic condition that impacts the adrenal glands.

Acting as a potent and selective oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist, crinecerfont works by reducing excessive adrenal androgen production, thus reducing the amount of glucocorticoid treatment needed. recommend managing the condition with supraphysiologic doses of glucocorticoids -- higher than those needed to treat adrenal insufficiency alone.

"Today's approval provides an important advance for patients with classic congenital adrenal hyperplasia and highlights the FDA's continued commitment to advancing effective and safe treatments for rare diseases," Theresa Kehoe, MD, director of the Division of General Endocrinology at FDA's Center for Drug Evaluation and Research, said in a statement.

Crinecerfont is the in 70 years for classic CAH and the only one that directly reduces excess adrenocorticotropic hormone, said developer Neurocrine Biosciences.

Underpinning the approval were two randomized placebo-controlled trials involving adults and pediatric patients. In the adult trial, 182 patients were randomized 2:1 to take crinecerfont or placebo twice daily for 24 weeks. Crinecerfont reduced daily glucocorticoid dose by 27% while maintaining control of androstenedione levels compared with a 10% daily glucocorticoid dose reduction in the placebo group.

As for the pediatric trial, the 69 patients who received crinecerfont twice daily had a significant reduction from baseline in serum androstenedione compared with an average increase from baseline in the 34 patients in the placebo group. By week 4, crinecerfont reduced the daily glucocorticoid dose by 18% while maintaining control of androstenedione levels versus a nearly 6% increase in daily glucocorticoid dose in the placebo group.

The open-label extension treatment portions of both studies are currently ongoing.

"We've been overtreating these people with glucocorticoids for a long time and, despite that, many of them still have elevated androgens, and they definitely have complications from long-term treatment -- obesity, diabetes, bone loss, etc.," trial investigator Richard Auchus, MD, PhD, of the University of Michigan Medical School in Ann Arbor, told 名媛直播 at ENDO 2024, where both trials were presented. "You generally have to make people toxic on glucocorticoids to control them."

Auchus said his team set out to find a way to treat these patients "with a more physiologic dose of glucocorticoids and yet maintain control of the androgens."

The most common adverse events with crinecerfont in adults were fatigue, dizziness, and arthralgia. Headache, abdominal pain, and fatigue were most common in pediatric patients.

Since crinecerfont is metabolized by the CYP3A4 enzyme, it shouldn't be used in conjunction with other and would thus reduce its efficacy.

The drug's label also warns of acute adrenal insufficiency or adrenal crisis, which can occur in those with underlying adrenal insufficiency who don't take adequate doses of glucocorticoid replacement therapy in situations associated with increased cortisol need (i.e., stress dose steroids).

When available, which is expected by next week, crinecerfont will come in 50-mg and 100-mg capsules and a 50-mg/mL oral solution.

Neurocrine said the medication will only be provided through PANTHERx Rare, a specialty pharmacy, to centralize and simplify prescription fulfillment.

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