Spruce Biosciences presented a late-breaking poster at the Annual Meeting of the Endocrine Society (ENDO 2019) outlining positive results from a phase II trial of tildacerfont for congenital adrenal hyperplasia (CAH).
The multicenter, multiple-dose, dose-escalation trial enrolled 18 patients with uncontrolled classic CAH. Ten patients in Cohort A received two weeks of treatment at each of three doses: 200, 600 and 1,000 mg tildacerfont once per day (QD) for a total of six weeks of treatment. Eight patients in Cohort B were treated for two weeks with 400 mg per day (200 mg twice per day [BID]). The study was designed to assess safety, tolerability, pharmacokinetics and the ability of tildacerfont to reduce adrenal androgens (androstenedione [A4]), progestins (17-hydroxyprogesterone [17-OHP]) and adrenocorticotropic hormone (ACTH), the primary driver of adrenal tissue hyperplasia. In Cohort A, improvements in A4 were demonstrated in 10 of 10 patients (100%), and 17-OHP and ACTH were both improved in 8 of 10 patients (80%). In Cohort B, improvements in A4 were demonstrated in 6 of 8 patients (75%), 17-OHP in 6 of 7 patients (86%) and ACTH in 5 of 7 patients (71%).
Additionally, after six weeks of treatment with tildacerfont, the one male patient with confirmed testicular adrenal rest tumors (TARTs) at baseline saw a notable reduction in tumor size after 6 weeks of therapy. Tildacerfont was well tolerated with no reported serious adverse events.
About Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) is a rare genetic disorder affecting the adrenal glands. People with CAH have an impaired ability to produce cortisol, also known as “the stress hormone,” which has an effect on energy, blood pressure, and the body’s response to stress, illness and injury. About 75% of CAH patients are unable to produce sufficient aldosterone, which helps the body maintain blood pressure and adequate levels of sodium. In some cases, those affected with CAH produce high levels of androgens. While both sexes need androgens for proper growth and development, an excess can cause problems including increased risk of testicular adrenal rest tumors (TART) in men, precocious puberty, short stature, hirsutism, virilization, and impairments to fertility.
There are currently no FDA-approved therapies. Patients are often prescribed supraphysiologic doses of steroids to suppress androgen production, which leads to the adverse effects associated with high dose steroids.
About Tildacerfont (SPR001)
Tildacerfont is small molecule that works by blocking CRF type-1 receptors on the pituitary gland to attenuate overproduction of ACTH, 17-OHP, and adrenal androgens.
Orphan Drug designation has been granted by both the U.S. FDA and the European Medicines Agency.