Spruce Biosciences Presents Phase 2 Data for Tildacerfont in Adults with Congenital Adrenal Hyperplasia at 23rd European Congress of Endocrinology
Tildacerfont Demonstrates Normalization of Elevated Hormone Levels Without Increases to Daily Steroid Doses
CAHmelia Clinical Program in Adult Classic CAH Underway to Assess Hormone and Steroid Reduction
SPR001-202 was an open-label, 12-week Phase 2a clinical trial, which assessed the ability of a daily dose of 400mg of tildacerfont to lower disease-driving hormones such as adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) over a 12-week dosing period. These hormones are used by physicians as a means of measuring the severity of CAH. Patients were classified into two groups based on disease control using these baseline hormone levels, defined as either poor disease control or good disease control.
Patients with poor disease control upon study entry had mean baseline levels of ACTH, 17-OHP and A4 that were significantly above the upper limit of normal. Administration of tildacerfont to these patients resulted in mean maximum reductions of 84% in ACTH, 80% in 17-OHP, and 79% in A4 compared to baseline across the study period. This enabled reduction in the levels of these key hormones to normal or near normal levels, including normalization of ACTH levels in 60% and normalization of A4 levels in 40% of poor disease control patients during month three. Normalization of these highly elevated hormones in classic CAH patients without increases to daily steroid doses has not been reported to date with any other investigational product candidate. Patients with good disease control upon study entry, achieved by supraphysiologic glucocorticoid dosing, had mean baseline levels of ACTH, 17-OHP and A4 that were below the upper limit of normal. Administration of tildacerfont to these patients did not lead to significant changes in these levels. While this study did not evaluate the ability of tildacerfont to reduce the need for high glucocorticoid dosing in patients with good disease control, this objective is an important unmet need due to the long-term and serious side effects associated with chronic use of high doses of glucocorticoids and is currently being evaluated in the CAHmelia-204 study.
“It is encouraging to see that tildacerfont, an oral, once-daily, and non-steroidal investigational therapy, produced meaningful reductions in highly elevated hormone levels for classic CAH patients, including, in some cases, normalization of these hormone levels over twelve weeks,” said
Spruce’s CAHmelia program in adult classic CAH patients is underway and actively enrolling in sites within
The presentation is on display in ECE 2021’s virtual poster hall. Learn more about the full program and how to access the poster presentation details on the ECE 2021 website.
Tildacerfont is a potent and highly selective, non-steroidal, oral antagonist of the CRF1 receptor, which is the receptor for corticotropin-releasing factor (CRF), a hormone that is secreted by the hypothalamus. The CRF1 receptor is abundantly expressed in the pituitary gland where it is the primary regulator of the HPA axis. By blocking the CRF1 receptor, tildacerfont has the potential to address the uncontrolled cortisol feedback regulatory pathway in CAH, and in turn reduce the production of ACTH in the pituitary, limiting the amount of androgen produced downstream from the adrenal gland. Tildacerfont has been evaluated in 171 patients across seven clinical trials in which it has been generally well tolerated. No drug-related serious adverse events have been reported related to tildacerfont treatment.
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the results, conduct, progress and timing of Spruce’s clinical trials. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “potential”, “suggests”, “demonstrates”, “may” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Spruce’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Spruce’s business in general, the impact of the COVID-19 pandemic, and the other risks described in Spruce’s filings with the