This morning, Millendo Therapeutics, Inc. announced topline results from a Phase 2 proof-of-concept study of its acyl-CoA acyltransferase 1 (ACAT1) inhibitor ATR-101 in congenital adrenal hyperplasia (CAH).
Based on the positive results and clinical benefit exhibited by ATR-101 in the study, Millendo stopped the trial earlier than originally scheduled, and the drug was recently granted Orphan Drug Designation by the U.S. Food and Drug Administration.
CAH, a disease of the endocrine system, is the result of a genetic mutation in an enzyme pivotal for the synthesis of cortisols. The condition is characterized by overgrowth of the adrenal glands, adrenal insufficiency, mineralocorticoid deficiency, and androgen excess. The most common symptom is severe dehydration.
The Phase 2 clinical trial (NCT02804178) enrolled 10 patients and evaluated the safety and efficacy of the orally-administered ATR-101 when added to corticosteroids in patients with CAH due to 21-hydroxylase deficiency. The study assessed 5 escalating doses, alternated between 2 weeks of treatment with ATR-101 and 2 weeks with placebo to determine the effects of ATR-101 on adrenal steroids.
“Treatment of patients with classic congenital adrenal hyperplasia is a difficult balance between the morbidities of androgen excess resulting from undertreatment with glucocorticoids and the morbidities of excess glucocorticoids due to overtreatment,” said Richard Auchus, M.D., Ph.D., Professor of Internal Medicine and Professor of Pharmacology, University of Michigan in a press release
. “While additional studies will need to be carried out, the results of this Phase 2 trial of ATR-101 give promise to patients in need of improvement with hormonal imbalances seen in CAH.”
Because of the demonstration of an apparent biological effect in 7 patients with marked reductions in 17α-Hydroxyprogesterone (17-OHP), enrollment was concluded at 10 patients. Mean decreases in 17-OHP were observed at all ATR-101 doses while mean escalations were seen during all placebo treatments. The primary endpoint of the study was a reduction in 17-OHP levels to ≤ 2 times the upper limit of normal, which was achieved by 2 patients. The result was consistent with the short duration of treatment (2 weeks/dose level) and high baseline levels.
ATR-101 was well-tolerated at all dose levels. It is also currently being investigated in a Phase 2 study for Cushing’s syndrome (NCT03053271) and a Phase 1 study for adrenocortical carcinoma (NCT01898715) at clinical sites in both the U.S. and Europe.
Per the NIH
, CAH is most commonly diagnosed at birth, and occurs in approximately 1 in every 15,000 births.
Full results from the study are expected to be presented at an upcoming medical meeting.
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