Dec. 17, 2024 – The FDA has approved crinecerfont, a first-in-class oral drug for treating classic congenital adrenal hyperplasia (CAH), a rare genetic condition present from birth. It is intended for patients ages 4 and older and should be used along with steroid medicines.
Classic CAH is a condition that affects the adrenal glands, located above each kidney. About 95% of CAH cases are caused by changes in the CYP21A2 gene, leading to a lack of the enzyme 21-hydroxylase. This prevents the adrenal glands from producing enough cortisol and aldosterone, hormones that help manage stress and regulate blood pressure. Instead, the glands produce excess male hormones (androgens), which can lead to abnormal bone growth in children, excess facial hair and menstrual problems in women, testicular tumors in men, and fertility issues in both sexes. If untreated, CAH can result in salt loss, dehydration, and even death.
The standard treatment for CAH involves high-dose glucocorticoids for maintaining cortisol levels and reducing excess levels of adrenal androgens. But high-dose glucocorticoids are often linked to serious side effects such as weight gain, diabetes, heart disease, and bone problems, along with mood and memory issues. This highlights the need for newer therapies that can manage the symptoms of CAH while cutting the side effects and complications caused by high-dose glucocorticoids.
Crinecerfont, marketed under the brand name Crenessity, works by blocking certain proteins (CRF1 receptors) in the brain's pituitary gland, which helps control the activity of the adrenal glands. This reduces the overproduction of adrenal androgens, allowing patients to take lower doses of glucocorticoids to maintain healthy cortisol levels.
Crenessity is the first new treatment for classic CAH in 70 years and offers a groundbreaking approach for treatment, according to Neurocrine Biosciences, the drug’s maker.
The FDA approved Crenessity based on two clinical trials involving 182 adults and 103 children with classic CAH. In the first study, 122 adults received Crenessity and 60 took a placebo, both taken twice a day for 24 weeks. After four weeks, those taking Crenessity showed a drop in androgen levels, allowing them to reduce their daily steroid dose by 27% – compared with a 10% reduction in the placebo group. Overall, androgen levels dropped eight times more than they did in the placebo group, and this improvement remained stable throughout the 24-week trial.
In the second study, 69 children received Crenessity and 34 received a placebo twice daily for 28 weeks. Children in the Crenessity group saw androgen levels fall to a level that was four times lower than seen in the placebo group, where levels increased. They were able to reduce their daily steroid dose by 18%, while the placebo group’s daily dose increased by 6%.
The most common side effects of Crenessity in adults include tiredness, dizziness, a poor appetite, muscle pain, backaches, and joint pain. Among children, headaches, stomach pain, a stuffy nose, nosebleeds, and tiredness were the common side effects. The FDA cautions that acute adrenal insufficiency can occur in patients with the condition who do not take enough steroid doses in times of stress.
Patients should inform their doctor of any severe injury, infection, illness, or planned surgery during treatment. And before taking Crenessity, they should share details of their medical history; pregnancy or breastfeeding plans; and any prescription and over-the-counter medicines, vitamins, and herbal supplements they are taking.
Neurocrine Biosciences announced in a news release that Crenessity will be commercially available as capsules (50-mg and 100-mg doses) and an oral solution (50 mg/ml) in 2025 through PANTHERx Rare, a specialty pharmacy, to simplify filling prescriptions.