Spruce Biosciences, Inc. provided an update on its clinical programs, anticipated upcoming milestones and strategic priorities for advancing tildacerfont in classic congenital adrenal hyperplasia (CAH) and polycystic ovary syndrome (PCOS). CAHmelia-203 Study for Adult Classic CAH: CAHmelia-203 is a randomized, double-blind, placebo-controlled, dose-ranging study evaluating the safety and efficacy of tildacerfont in adult patients with classic CAH and is designed to enroll approximately 72 patients with high levels of androstenedione (A4) while on their current glucocorticoid regimen. Enrollment in the clinical trial is approaching 50%. Anticipated Upcoming Milestone: Topline results in the second half of 2023 CAHmelia-204 Study for Adult Classic CAH: CAHmelia-204 is a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of tildacerfont in adult patients with classic CAH. The study is designed to enroll approximately 90 patients on supraphysiologic doses of glucocorticoids at or above 30 mg/d hydrocortisone equivalent with normal or near normal levels of A4. Enrollment in the clinical trial recently surpassed 25%. Anticipated Upcoming Milestone: Topline results in the second half of 2024. Phase 2 CAHptain Clinical Study in Pediatric Classic CAH: Spruce is investigating tildacerfont for the treatment of classic CAH in children. There is a significant medical need to bring ndrogen-lowering and glucocorticoid-sparing therapies to pediatric classic CAH patients to reduce the risk of premature puberty and the adverse effects of glucocorticoids, including stunted growth resulting in short stature as adults. The Phase 2 open-label clinical trial utilizes a sequential 3 cohort design (cohorts 1 and 2 comprising of adolescent patients 11 to 17 years of age, and cohort 3 comprising of children 2 to 10 years of age) to evaluate the safety, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) of tildacerfont in children 2 to 17 years of age with classic CAH. Spruce implemented key protocol changes to nhance the study design and gather additional data to inform future clinical development: Spruce amended the study length from a2-week PK and exploratory PD study to a 12-week study. The company plans to also offera2-year open-label extension to the 12-week study. These changes are designed to enable patients to retain access to the study drug for up to 2 years following completion of the study, and provide for observation of clinical outcomes, such as bone age and predicted adult height. The company is lowering the minimum age requirement from 6 years to 2 years of age. Given the significant growth and development that occurs in children between the ages of 2 years and 5 years of age, this change is designed to provide important data on the impact of reductions in androgen levels and glucocorticoids (GC) in younger children. The following additional data will be collected to inform a potential Phase 3 registrational clinical trial, while allowing for observation of key clinical outcomes:
2 weeks of pediatric tildacerfont PK exposure data at two weight adjusted doses (50mg and 200mg) to inform a dose for the Phase 3 registrational program;
4 weeks of PD data to potentially show reduction in androstenedione (A4) and establish dose-response (day 1-28);
A4 reduction data and GC reduction based on a protocol-specified algorithm (day 28-90); and
sub-chronic safety data at 12 weeks.