Spruce Biosciences has trimmed the only drug from its pipeline in the wake of a second phase 2 failure this year, leaving the biotech’s future direction uncertain.
The CRF1 receptor antagonist, called tildacerfont, was being investigated in the CAHmelia-204 trial of 100 adults with classic congenital adrenal hyperplasia (CAH), meaning they had normal or near-normal levels of a steroidal hormone called androstenedione.
The phase 2b study failed to hit the primary endpoint of reducing the use of glucocorticoids (GC) in these individuals by Week 24, the biotech explained in a postmarket release Dec. 10. These individuals were receiving a mean GC dose of 35 mg/day of hydrocortisone equivalents, with a 200-mg daily dose of tildacerfont only reducing the GC dose taken by an average of 0.7 mg.
It follows a midstage failure for tildacerfont in severe CAH in March, where the drug was unable to demonstrate a reduction in androstenedione levels from baseline at Week 12. At the time, the company’s stock plunged from around the $5 mark to less than $1 and has never recovered.
CAH spans a group of genetic conditions that result in an enzyme deficiency that alters the production of adrenal hormones. Around 95% of cases are caused by a mutation that leads to a deficiency of the enzyme 21-hydroxylase, and there are currently no FDA-approved non-glucocorticoid treatments available.
The company also used yesterday’s announcement to provide an update on a separate trial, CAHmelia-205, which was evaluating the pharmacodynamics and pharmacokinetics of various doses of tildacerfont in pediatric and adult patients with CAH. Spruce didn’t spell out whether this study had also failed, instead pointing to a “trend … observed of larger reductions from baseline in [androstenedione] levels with higher BID doses of tildacerfont.”
Still, based on the readouts, the company said it is discontinuing both the CAHmelia-204 and CAHptain-205 trials and “winding down Spruce’s investment in tildacerfont for the treatment of CAH as we conserve financial resources and look to maximize shareholder value.”
With no other drugs listed in the biotech’s pipeline, it’s unclear where Spruce goes from here. CEO Javier Szwarcberg, M.D., said that “moving forward, we plan to evaluate a full range of strategic options for Spruce in addressing diseases with serious unmet need for patients.”
“We garnered invaluable safety and exposure response data on tildacerfont from these studies, which suggests that higher doses and more frequent dosing may be necessary for efficacy in CAH,” the CEO added.
Spruce’s surrender of the CAH space leaves a path clear for Neurocrine Biosciences, which is awaiting an FDA approval decision at the end of this month for its CRF1 receptor antagonist crinecerfont as a treatment for CAH. Crinecerfont has already demonstrated the ability to reduce both glucocorticoid use and androstenedione levels in phase 3 trials in adults and children last year.