Congenital adrenal hyperplasia (CAH) is a rare disease caused by a genetic mutation that results in a deficiency of the enzyme 21-hydroxylase and impairs the synthesis of cortisol, a hormone essential for normal physiological functions. The body tries unsuccessfully to compensate for this deficiency and as a result triggers excessive production of adrenal androgen hormones, leading to further complications. Patients are currently treated with supraphysiological doses of glucocorticoids, which can cause serious side effects such as weight gain, diabetes, cardiovascular disease, infertility and osteoporosis.

The results of the phase 3 trial of Crinecerfont, a compound that may offer significant benefits to both adult and paediatric patients, bring a new option to the treatment paradigm for this disease. The results of the study, published in the New England Journal of Medicine and presented at the last edition of ENDO, the most important international conference on endocrinology, involved more than fifty research centres in ten countries, including Sapienza University of Rome and Federico II University of Naples. 

The new therapeutic approach is able to keep adrenal androgen production under control without having to resort to excessive and harmful doses of glucocorticoids.

In particular, of the 176 adult patients who took part in the study, the group treated with Crinecerfont showed a 27.3% reduction in glucocorticoid dose compared with 10.3% in the placebo group, while 63% of participants achieved physiological hormone levels despite the disease (compared with 18% in the placebo group). The most common adverse events were fatigue, headache, fever and vomiting, but these were episodic and similar in the two groups.

"Controlling the disease is a difficult balancing act between the complications of androgen excess, growth and development problems, male and female reproductive problems, and other problems related to chronic exposure to too many glucocorticoids, which the more than 4,000 patients in Italy are currently exposed to," says Andrea Isidori from the Department of Experimental Medicine of Sapienza. "This result was also possible thanks to the collaboration between paediatric and adult endocrinology centres, in the framework of the pathways indicated by Europe within the Reference Network for Rare Diseases (ENDO-ERN), of which the University General Hospitals are part, and the commitment of the universities in their Outreach activities."

“Crinecerfont could revolutionise the management of congenital adrenal hyperplasia by significantly reducing the required dose of glucocorticoids, thus limiting long-term side effects”, adds Rosario Pivonello of the Department of Medical Medicine and Surgery at the Federico II University.

References:

Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia - Richard J. Auchus, Oksana Hamidi, Rosario Pivonello, Irina Bancos, Gianni Russo, Selma F. Witchel, Andrea M. Isidori et al. - The New England Journal of Medicine – DOI: 10.1056/NEJMoa2404656

Further Information

Andrea Isidori
Department of Experimental Medicine 
andrea.isidori@uniroma1.it