Nonsteroidal treatment shows promise for congenital adrenal hyperplasia

Adults with classic congenital adrenal hyperplasia who received a once-daily, nonsteroidal oral therapy for 12 weeks experienced significant reductions in androgen levels with no serious adverse events, according to findings from a phase 2a study.

Richard Auchus

Tildacerfont (Spruce Biosciences) is an investigational, once-a-day corticotropin-releasing factor type-1 receptor antagonist in development for the treatment of congenital adrenal hyperplasia (CAH) that directly targets adrenocorticotropic hormone (ACTH), according to a press release from the company.

“There is a significant and urgent need for new CAH treatments, as there are currently no FDA-approved therapies,” study investigator Richard Auchus, MD, PhD, professor of internal medicine and pharmacology in the division of metabolism, endocrinology and diabetes at the University of Michigan, said in the release. “The results of this study are encouraging, as they demonstrate for the first time that a novel nonsteroidal treatment can produce clinically meaningful reductions across key biomarkers over a period of 12 weeks. These data indicate tildacerfont could be a promising new treatment option for patients with CAH.”

The multicenter, open-label phase 2a study enrolled 11 adults with classic CAH and elevated androgen levels at baseline, and they were treated with 400 mg tildacerfont once daily for 12 weeks. At the end of the study, researchers observed mean reductions from baseline of 74% for ACTH, 82% for the steroid hormone 17-hydroxyprogesterone (17-OHP) and 55% for androstenedione.

Maximum mean reductions observed at any time point in the study were 84% for ACTH, 82% for 17-OHP and 79% for androstenedione. Additionally, 60% of patients with elevated, abnormal ACTH levels and 40% of patients with elevated androstenedione levels experienced reductions to normalization by week 12. The primary endpoint of safety and tolerability was achieved, with no new safety signals observed in the study. Most adverse events were classified as mild and not related to study drug. There were no serious adverse events.

“The magnitude of these reductions coupled with patients having been able to achieve normalization after only 12 weeks of treatment suggests that tildacerfont may provide a first-in-class option for patients to better manage their disease by reducing their exposure to elevated androgens and, potentially, their lifelong steroid burden,” Richard King, CEO of Spruce Biosciences, said in the release.

In 2018, the Endocrine Society released an updated clinical practice guideline for the management of CAH, noting the condition requires a shared decision-making approach that incorporates providers, families and the best interest of the patient, with an effort to consider and incorporate quality of life and psychosocial health concerns,

In an analysis published in January 2017 in the European Journal of Endocrinology and reported by Endocrine Today, researchers wrote that new therapies are needed to better address the comorbidities associated with CAH. The researchers wrote that patient education about the risks of the disease and the long-term use of glucocorticoids as a treatment for the disease is necessary. – by Regina Schaffer

Disclosures: King is CEO of Spruce Biosciences. Endocrine Today could not confirm relevant financial disclosures for Auchus at the time of publication.

Adults with classic congenital adrenal hyperplasia who received a once-daily, nonsteroidal oral therapy for 12 weeks experienced significant reductions in androgen levels with no serious adverse events, according to findings from a phase 2a study.

Richard Auchus

Tildacerfont (Spruce Biosciences) is an investigational, once-a-day corticotropin-releasing factor type-1 receptor antagonist in development for the treatment of congenital adrenal hyperplasia (CAH) that directly targets adrenocorticotropic hormone (ACTH), according to a press release from the company.

“There is a significant and urgent need for new CAH treatments, as there are currently no FDA-approved therapies,” study investigator Richard Auchus, MD, PhD, professor of internal medicine and pharmacology in the division of metabolism, endocrinology and diabetes at the University of Michigan, said in the release. “The results of this study are encouraging, as they demonstrate for the first time that a novel nonsteroidal treatment can produce clinically meaningful reductions across key biomarkers over a period of 12 weeks. These data indicate tildacerfont could be a promising new treatment option for patients with CAH.”

The multicenter, open-label phase 2a study enrolled 11 adults with classic CAH and elevated androgen levels at baseline, and they were treated with 400 mg tildacerfont once daily for 12 weeks. At the end of the study, researchers observed mean reductions from baseline of 74% for ACTH, 82% for the steroid hormone 17-hydroxyprogesterone (17-OHP) and 55% for androstenedione.

Maximum mean reductions observed at any time point in the study were 84% for ACTH, 82% for 17-OHP and 79% for androstenedione. Additionally, 60% of patients with elevated, abnormal ACTH levels and 40% of patients with elevated androstenedione levels experienced reductions to normalization by week 12. The primary endpoint of safety and tolerability was achieved, with no new safety signals observed in the study. Most adverse events were classified as mild and not related to study drug. There were no serious adverse events.

“The magnitude of these reductions coupled with patients having been able to achieve normalization after only 12 weeks of treatment suggests that tildacerfont may provide a first-in-class option for patients to better manage their disease by reducing their exposure to elevated androgens and, potentially, their lifelong steroid burden,” Richard King, CEO of Spruce Biosciences, said in the release.

In 2018, the Endocrine Society released an updated clinical practice guideline for the management of CAH, noting the condition requires a shared decision-making approach that incorporates providers, families and the best interest of the patient, with an effort to consider and incorporate quality of life and psychosocial health concerns,

In an analysis published in January 2017 in the European Journal of Endocrinology and reported by Endocrine Today, researchers wrote that new therapies are needed to better address the comorbidities associated with CAH. The researchers wrote that patient education about the risks of the disease and the long-term use of glucocorticoids as a treatment for the disease is necessary. – by Regina Schaffer

Disclosures: King is CEO of Spruce Biosciences. Endocrine Today could not confirm relevant financial disclosures for Auchus at the time of publication.