Nearly 70% of Adults With Classic CAH Reach Physiologic GC Dosing With Crinecerfont

2-year data from the CAHtalyst Adult Study suggest treatment with crinecerfont (Crenessitys) enables sustained reductions in glucocorticoid (GC) exposure among adults with classic congenital adrenal hyperplasia (CAH), with nearly 70% of participants achieving physiologic replacement dosing after 24 months.

Presented at the Endocrine Society (ENDO) Annual Meeting 2026, the analysis showed participants maintained substantial reductions in GC doses through 2 years of treatment while generally preserving androgen control, addressing a longstanding challenge in CAH management. Historically, many patients require chronic supraphysiologic GC doses to suppress excess adrenal androgen production, exposing them to increased risks of obesity, hypertension, insulin resistance, osteoporosis, and other complications.

"At 24 months, 71% of patients were able to achieve physiological corticoid dose replacement, defined as hydrocortisone equivalent less than 11 milligram per meter square per day," Oksana Hamidi, DO, associate professor in the division of endocrinology and metabolism at UT Southwestern Medical Center, told HCPLive. "That was definitely a significant and very meaningful finding."

Sustained Reductions in Glucocorticoid Exposure

The phase 3 CAHtalyst Adult Study (NCT04490915) enrolled 182 adults with classic CAH. Participants completed a 24-week double-blind, placebo-controlled phase followed by a 6-month open-label period and an ongoing open-label extension.

At baseline, participants were receiving a mean total daily GC dose of 17.6 mg/m²/day, equivalent to 32.3 mg/day hydrocortisone.

Investigators evaluated GC dose reductions using 2 approaches. The primary analysis assessed dose reductions while maintaining or improving androstenedione (A4) levels relative to baseline. Under this method, any GC reduction associated with worsening A4 was imputed to zero.

Using this more conservative analysis, mean GC dose reductions were 26% at Month 12, 28% at Month 18, and 25% at Month 24. At Month 24, 45% of participants achieved physiologic GC dosing of ≤11 mg/m²/day while maintaining or improving A4 control.

Investigators also examined observed GC doses at Months 18 and 24, reflecting real-world clinical decision-making after protocol-mandated titration requirements ended.

The observed analysis demonstrated larger reductions, with mean GC doses decreasing by 38% from baseline at both Month 18 and Month 24. Mean observed GC dose fell to 10.6 mg/m²/day (19.4 mg/day), and 69% of participants at Month 24 achieved physiologic replacement dosing.

"When we are representing the data, it's important to know the methods behind it," Hamidi said. "More real-world data would be the observed glucocorticoid dose reduction."

She explained that the observed-dose analysis reflects clinician-guided dose adjustments based on laboratory values, tolerability, and individual patient circumstances rather than protocol-driven requirements.

Implications Beyond Androgen Control

According to Hamidi, the significance of the findings extends beyond reductions in GC dose alone.

Patients entered the study receiving a mean hydrocortisone-equivalent dose of approximately 32 mg/day, substantially above physiologic replacement levels. Despite these reductions, investigators reported relatively stable A4 levels through Month 24, with mean changes of -11.5 ng/dL at Month 18 and +56.6 ng/dL at Month 24.

Hamidi noted that reducing chronic GC exposure may ultimately translate into improvements in metabolic health and quality of life.

"I want to see improvements in patients' weight, blood pressure measurements, as well as body composition changes that are favorable," she said. "I hope that we are able to improve quality of life of patients who have low quality of life at the beginning."

Safety Considerations

Crinecerfont was generally well tolerated through 24 months, with no new safety signals identified.

Investigators reported several cases of adrenal insufficiency and adrenal crisis, underscoring the importance of patient education regarding stress dosing and crisis prevention during GC dose reduction. One fatal event occurred in a participant with cholecystitis and bacterial infection during the open-label extension; investigators considered the event unlikely to be treatment-related.

As clinicians begin incorporating crinecerfont into routine practice, Hamidi recommended a gradual approach.

"I always advocate for making one change at a time," she said. "Brand new medication, start with that first, observe that patient, check their levels, see how they're doing, then potentially consider glucocorticoid dose reduction, if that's applicable."

Editor’s Note: Hamidi reports relevant disclosures with Corcept Therapeutics, Neurocrine Biosciences, Xeris Pharma, Camurus, Crinetics Pharmaceuticals, and Recordati Rare Diseases.

References

1. Bancos I, Hamidi O, Kiefer FW, et al. Adults with classic congenital adrenal hyperplasia taking crinecerfont demonstrated sustained decreases in glucocorticoid doses: 2-year results from the CAHtalyst Adult Study. Poster presented at: ENDO 2026; June 14, 2026; Chicago, IL.

2. Hillenbrand A. Crinecerfont sustains glucocorticoid reduction, improves cardiometabolic outcomes in classic CAH. HCPLive. Published June 15, 2026. Accessed June 18, 2026. https://www.hcplive.com/view/crinecerfont-sustains-glucocorticoid-reduction-improves-cardiometabolic-outcomes-in-classic-cah