FDA Approves New Treatment for Congenital Adrenal Hyperplasia

he U.S. Food and Drug Administration (FDA) has approved Crenessity (crinecerfont) for use in combination with glucocorticoids (steroids) to help manage androgen (testosterone-like hormone) levels in both adult and pediatric patients aged 4 years and older with classic congenital adrenal hyperplasia (CAH).

“This approval marks an important step forward for patients with classic congenital adrenal hyperplasia and underscores the FDA’s ongoing commitment to advancing safe and effective treatments for rare diseases,” said Dr. Theresa Kehoe, director of the Division of General Endocrinology at the FDA’s Center for Drug Evaluation and Research. “We will continue to collaborate with patients, pharmaceutical companies, and healthcare providers to address the unmet medical needs of the rare disease community.”

Classic congenital adrenal hyperplasia is a rare genetic disorder affecting the adrenal glands, which produce hormones like cortisol and androgens. Patients with classic CAH do not produce enough cortisol and produce an excess of androgens. These patients require high doses of glucocorticoids (more than typically needed to replace the deficient cortisol) to help reduce the excess androgen levels. Crenessity works by lowering excessive adrenal androgen production, thereby helping to reduce the amount of glucocorticoid treatment required.

Crenessity’s approval is supported by two randomized, double-blind, placebo-controlled trials involving 182 adults and 103 children with classic CAH. In the first trial, 122 adults received Crenessity twice daily, while 60 received a placebo for 24 weeks. After the first four weeks, the glucocorticoid dose was reduced to replacement levels and adjusted based on androstenedione (an androgen hormone) levels. The primary measure of efficacy was the change in the total daily glucocorticoid dose from baseline while maintaining androstenedione control by the end of the trial. The group receiving Crenessity reduced their glucocorticoid dose by 27% while maintaining androstenedione control, compared to a 10% reduction in the placebo group.

In the second trial, 69 pediatric patients received Crenessity twice daily, and 34 received a placebo for 28 weeks. The primary measure of efficacy was the change in serum androstenedione levels at week 4. The Crenessity group showed a statistically significant reduction in serum androstenedione, while the placebo group showed an average increase. By the end of the trial, Crenessity-treated patients were able to reduce their glucocorticoid dose by 18%, while placebo-treated patients experienced an almost 6% increase in their glucocorticoid dose.

Crenessity carries a warning for acute adrenal insufficiency or adrenal crisis, which can occur in patients with underlying adrenal insufficiency who do not receive adequate glucocorticoid replacement therapy during situations requiring increased cortisol levels (e.g., “stress dose steroids”). Crenessity should not be used by individuals with hypersensitivity to its active ingredient or any of its components.

Because Crenessity is metabolized by a specific enzyme, using it alongside drugs that activate this enzyme can reduce Crenessity exposure and decrease its effectiveness. Information about recommended dose adjustments is provided in Crenessity’s full prescribing information.

The most common side effects in adults include fatigue, dizziness, and joint pain (arthralgia), while pediatric patients may experience headache, abdominal pain, and fatigue.

The FDA granted Crenessity Fast Track, Breakthrough Therapy, Orphan Drug, and Priority Review designations.