Spruce scores phase 2a win for rare disease drug, gears up for 2020

Tildacerfont is a daily pill that works by blocking corticotropin-releasing factor type 1 receptors to slash the production of adrenocorticotropic hormone. (Pixabay)

Spruce Biosciences is one step closer to a treatment for congenital adrenal hyperplasia (CAH). New phase 2a data show the drug reduced the level of three hormones overproduced by patients with CAH, teeing it up for its next trial, which will gauge whether it can replace the large amounts of steroids currently used to treat the disorder. That study is slated to start in 2020. 

San Francisco-based Spruce is focused on the most common form of CAH, which stems from a mutation in the gene that codes for the enzyme 21-hydroxylase. Without this enzyme, people with CAH can’t make certain hormones, such as cortisol, and they overproduce other hormones called androgens. 

Its drug, tildacerfont, is a daily pill that works by blocking corticotropin-releasing factor (CRF) type 1 receptors to slash the production of adrenocorticotropic hormone (ACTH). Though the drug directly targets ACTH, it also affects the levels of other hormones that are downstream from ACTH: 17-hydroxyprogesterone (17-OHP) and androstenedione (A4). 

The phase 2a study tested tildacerfont in 24 patients, according to ClinicalTrials.gov. After 12 weeks of treatment, the drug lowered ACTH levels an average of 74% from baseline, Spruce said in a statement. The average reduction from baseline was 82% for 17-OHP and 55% for A4. More than half of the patients saw their ACTH come down to normal levels. 

RELATED: With positive phase 2, Neurocrine eyes pivotal trial for rare disease drug

“Almost all patients tended toward substantial improvement,” Spruce CEO Richard King told FierceBiotech. “We did see about 60% of patients normalize for ACTH and 40% for A4 levels in the study. I do anticipate over 16 weeks, those numbers would improve, given that at 12 weeks we are still seeing downward trending.” 

Tildacerfont would be a nonsteroid treatment for patients who rely on high doses of glucocorticoids to manage their disease. These steroids aim to replace the cortisol CAH patients don’t produce as well as tamp down on the excess androgens they do make. But they aren’t a perfect solution—“Very few patients have their androgens controlled even with glucocorticoids,” King said, and they come with the usual side effects of steroids such as osteoporosis and cardiovascular and metabolic issues. 

Tildacerfont won’t be able to cut out steroids entirely, as patients will still need them to replace the cortisol they don’t produce. But these doses would be far lower than the “supraphysiologic” levels of steroids CAH patients typically take. 

Now that Spruce has shown tildacerfont can cut androgen levels, it will kick off a study next year to test tildacerfont’s ability to reduce the need for steroids, King said. 

The company is trailing Neurocrine Biosciences, which reported phase 2 data for its CRF antagonist in March, and is in talks with the FDA about a path to registration.