SAN DIEGO, June 15, 2026
Neurocrine Biosciences has unveiled new two-year data from its Phase 3 CAHtalyst® Adult study, demonstrating that CRENESSITY® (crinecerfont) delivered meaningful improvements in cardiometabolic health, body composition, insulin resistance and bone-related outcomes in adults living with classic congenital adrenal hyperplasia (CAH). The findings, presented at ENDO 2026 in Chicago, highlight the potential of CRENESSITY to address some of the most significant long-term complications associated with chronic glucocorticoid therapy while maintaining disease control. Adults treated with CRENESSITY experienced sustained reductions in glucocorticoid exposure alongside improvements in weight management, metabolic health and quality of life, reinforcing the growing role of the therapy in transforming lifelong management of this rare endocrine disorder. The results provide important evidence supporting the long-term benefits of reducing excessive steroid dependence in adults with CAH.
Two-Year Data Show Sustained Improvements in Weight and Insulin Resistance
The latest analysis evaluated adults who continued treatment with CRENESSITY through the ongoing open-label extension of the Phase 3 study. Researchers reported significant and sustained reductions in daily glucocorticoid dosing, with average doses decreasing by approximately 38% over two years while maintaining androgen control. These reductions were accompanied by meaningful improvements in several cardiometabolic measures. Among participants who were overweight or obese at baseline, 37% achieved greater than 5% body weight reduction after two years of treatment, a clinically meaningful outcome associated with improved long-term health. Investigators also observed reductions in body mass index and favorable changes in body composition, with fat mass decreasing while lean muscle mass was preserved.
Importantly, insulin resistance improved substantially during treatment. Among patients with insulin resistance at baseline, 43% were no longer classified as insulin resistant after two years, suggesting that sustained hormonal control combined with lower glucocorticoid exposure may significantly reduce future cardiometabolic risk. These findings are particularly important given the high prevalence of obesity, metabolic dysfunction and cardiovascular complications among adults with classic CAH.
Bone Health and Quality of Life Outcomes Continue to Improve
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Beyond metabolic outcomes, Neurocrine also reported encouraging trends in bone health, another area commonly affected by long-term exposure to supraphysiologic glucocorticoid doses. Researchers observed favorable improvements in bone mineral density measurements in the lumbar spine and total hip, with the most notable gains occurring in glucocorticoid-sensitive regions of the skeleton. Bone turnover markers also suggested recovery from the suppressive effects associated with prolonged steroid use, supporting the possibility of improved skeletal health over time. Patient-reported outcomes further reinforced the clinical benefits of treatment.
In a survey of adults participating in the study’s open-label extension, 96% reported satisfaction with CRENESSITY, while 98% indicated they would recommend the therapy to others living with CAH. Respondents also reported greater optimism about their future health, improved confidence in disease management and reduced concern regarding long-term complications associated with high-dose glucocorticoid treatment. These findings highlight the broader impact of therapy beyond laboratory measurements and clinical endpoints, demonstrating meaningful improvements in everyday patient experience.
Potential to Redefine Long-Term Management of Classic CAH
Classic congenital adrenal hyperplasia is a rare genetic disorder characterized by impaired cortisol production and excessive androgen secretion, often requiring lifelong glucocorticoid replacement therapy. Historically, patients have required supraphysiologic steroid doses to suppress elevated ACTH and androgen levels, increasing the risk of obesity, diabetes, cardiovascular disease, osteoporosis and other chronic complications. CRENESSITY works through a non-glucocorticoid mechanism by selectively antagonizing corticotropin-releasing factor type 1 (CRF1) receptors, reducing ACTH production and helping control excess adrenal androgen levels. According to Neurocrine Biosciences, the therapy enables patients to achieve disease control while lowering glucocorticoid exposure to more physiologic levels.
Across all analyses, CRENESSITY remained generally well tolerated with no new safety signals observed during long-term follow-up. As the first approved therapy of its kind for classic CAH, CRENESSITY continues to build a strong body of evidence supporting its potential to improve metabolic health, bone outcomes and overall quality of life. The new ENDO 2026 findings further position the therapy as a potentially transformative treatment option capable of redefining the standard of care for adults living with this lifelong endocrine condition.
Source: Neurocrine Biosciences press release
