The Food and Drug Administration (FDA) of the United States has recently approved Crenessity (crinecerfont) to be used along with the glucocorticoids in managing the androgen levels in patients suffering from Congenital adrenal hyperplasia (CAH) of classical form. This approval works both for adults and pediatric patients aged four years old and above.
CAH is a rare genetic disorder that affects the functions of adrenal glands thereby causing less production of cortisol and increased levels of androgen. Dr. Theresa Kehoe, head of the Division of General Endocrinology at the FDA Centre for Drug Evaluation and Research (CDER) has prioritized that the FDA decision is one of the significant steps forward in meeting the requirements of rare illness patients.
The FDA’s approval was based on data from two well-controlled clinical trials which is considered to evaluate the safety and efficacy of Crenessity. Both studies were randomized, double-blind, and placebo-controlled that included 285 patients with classic CAV.
Trial 1: This study involved 182 adult participants of which 122 were administered with Crenessity twice a day while 60 were given placebo for a period of 24 weeks. During the first four weeks, the glucocorticoids dose was decreased to a physiological level and in accordance with the androgen hormone androstenedione. The decrease in total daily glucocorticoid dosage while preserving androstenedione control was the key effectiveness goal.
Trial 2: In the pediatric-orientated trial, 103 patients over the age of 4 years participated in the study, 69 patients took Crenessity while 34 patients were given a placebo for 28 weeks. The outcomes determined by the trial were a reduction in the serum androstenedione concentration at week 4. Secondary outcomes were the added ability to decrease the dosing of glucocorticoid levels and to still maintain the androstenedione control.
The trials demonstrated the efficacy of Crenessity in reducing glucocorticoid dependency and controlling androgen levels:
Adult Trial Outcomes: Compared to placebo, the glucocorticoid dose was reduced by 27% with Crenessity androstenedione controlled while it was reduced by only 10% in the placebo control group.
Pediatric Trial Outcomes: The serum androstenedione level in children receiving Crenessity declined at week 4 whereas the placebo group registered an average rise in the same level. Furthermore, the Crenessity group decreased their daily glucocorticoid doses by 18% while the placebo group increased it by about 6%.
Crenessity presents a new approach to classic CAH treatment targeting the overproduction of adrenal androgens directly. This mechanism helps in avoiding high glucocorticoid doses which otherwise are used in suppressing androgen levels but have long-term side effects.
The trials provide evidence of the possibilities of increasing the quality of a patient’s life while using Crenessity to restore the hormonal balance with fewer levels of glucocorticoids. This risk can therefore be managed by ensuring that adequate glucocorticoid replacement is availed. This risk can however be minimised by ensuring appropriate glucocorticoid replacement.
The side effects observed in the studies ranged in intensity from mild to moderate. In adults, most of the side effects reported were as follows: fatigue dizziness, and joint pains. The common complaints among pediatric patients include headaches, abdominal pain, and fatigue. These results are indicative of a relatively benign risk profile but would support the continued assessment of risk and the delivery of prevention services.
The FDA approval of Crenessity makes a new advancement in the management of classic CAH. In using this therapy, its benefits outweigh its risks though the risks of adrenal insufficiency and drug interaction must be carefully managed.
This approval represents the FDA’s drive towards improving treatment for rare diseases for people and their families living with the challenges of classic CAH. A large-scale clinical investigation, post-marketing surveillance, and follow-up study should be conducted to determine the safety and effectiveness/efficacy of Crenessity in various subpopulations.
For comprehensive details on Congenital Adrenal Hyperplasia, explore our dedicated page – Congenital Adrenal Hyperplasia.
References: U.S. Food and Drug Administration. FDA approves new treatment for congenital adrenal hyperplasia. 2024. Accessed January 2, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-congenital-adrenal-hyperplasia
