Spruce Biosciences shared results from two Phase II studies assessing tildacerfont, a non-steroidal, oral antagonist for the treatment of adult patients with classic CAH.
Two mid-stage clinical trials showed that treatment with a non-steroidal, oral antagonist generated meaningful reductions in elevated hormones in adult patients diagnosed with classic Congenital Adrenal Hyperplasia (CAH).
On Monday, Bay Area-based Spruce Biosciences shared results from two Phase II studies assessing tildacerfont, SPR001-201, a Phase IIa dose-escalation study and SPR001-202, a Phase IIa, a dose focusing on the efficacy of a 400mg dose on multiple biomarkers.
The trial data showed that over a 12 week period use of tildacerfont, an oral antagonist of the CRF1 receptor, was able to reduce the elevated hormone levels and, in some cases, actually normalized them. The company called this a notable achievement. It said no other investigational drug candidate had reported these kinds of results. The study data was published in the Journal of Clinical Endocrinology and Metabolism.
Congenital adrenal hyperplasia (CAH) typically refers to a group of genetic disorders that impact the adrenal glands, which produce numerous hormones, including cortisol, mineralocorticoids and androgens. CAH prevents an individual from being able to produce one or more of these hormones. CAH is something infants are tested for shortly after birth. Treatment has involved long-term use of glucocorticoids, which creates worrisome side effects, including obesity, decreased ability to absorb calcium, elevated cholesterol and an increased risk of gastritis.
A lack of treatment means CAH patients will often have an accelerated onset of puberty, typically beginning between ages five and seven. Other issues can be alopecia, excess body hair, shorter statures, significant acne, and later in life, fertility issues. There are approximately 30,000 cases of CAH in the United States and about 50,000 in the European Union.
Spruce Biosciences believes that by blocking the CRF1 receptor, tildacerfont has the potential to address the uncontrolled cortisol feedback regulatory pathway in CAH. In turn, this can reduce ACTH production in the pituitary, limiting the amount of androgen produced downstream from the adrenal gland, the company said.
Spruce Biosciences Chief Executive Officer Richard King told BioSpace that there has been little advancement in treating CAH over the past 50 years. The decision to treat with a lifetime of glucocorticoids or opting to not treat it leads to a “damned if you do, damned if you don’t” scenario. Clinical data from these Phase IIa studies, as well as ongoing trials, indicate tildacerfont could be the first treatment for these patients. Calling the lack of treatment unfair, King expressed his hope in the research Spruce Biosciences is conducting. He said the company’s research team is primarily focused on this condition and is working with patient advocacy groups as they strive toward the regulatory goal.
“If we can get to a place where we can get to an alternative to pure steroids (for the patients), we’ll be thrilled with that,” King said.
SPR001-201 evaluated the tildacerfont’s capabilities to lower adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) at multiple dosing levels in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The Phase IIa SPR001-202 measured a daily 400mg dose of tildacerfont to lower ACTH, 17-OHP, and A4 over a 12-week dosing period. In both studies, efficacy was evaluated by changes from baseline in ACTH, 17-OHP, and A4 according to baseline measurements that characterized patients as having good or poor disease control.
Spruce Biosciences Chief Medical Officer Rosh Dias said classic CAH could be life-threatening, and treatment options have been limited.
“People living with classic CAH must grapple with the difficult balance of managing their adrenal androgen excess and supraphysiologic dosing of glucocorticoids, the existing standard of care therapy,” Dias said in a statement.
“In our Phase IIa studies, I was pleased to see that tildacerfont was able to produce meaningful reductions in highly elevated hormones in classic CAH patients, including in some cases normalization of these hormones, over a 12-week period without increases to daily steroid doses. This has not been reported to date with any other investigational product candidate,” she added.
Results from both Phase IIa studies showed that treatment with tildacerfont reduced key hormone biomarkers towards normal levels, including the normalization of adrenocorticotropic hormone (ACTH) and A4 in 60% and 40% of patients in the baseline poor disease control group. In the good disease control group, the hormones were maintained near or below normal levels.
The company noted that the Phase IIa results support the continued development of tildacerfont as a potential treatment for classic CAH. The company has planned Phase IIb studies to assess tildacerfont’s capabilities to reduce excessive adrenal androgens in patients with poor disease control, as well as a study to assess the oral antagonist’s capabilities to reduce glucocorticoid usage in patients with good disease control while maintaining control of androgens. King said he hopes those will trials will be positive enough for Spruce Biosciences to seek regulatory approval of tildacerfont for CAH.
“This drives the work we do each day,” King added.
