Trial in Progress: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ATR-101 for the Treatment of Cushing’s Syndrome

Presentation Number: SAT 410
Date of Presentation: April 1st, 2017

Vivian H Lin*, Marian Ijzerman, Marianne R Plaunt and Pharis Mohideen
Millendo Therapeutics, Inc., Ann Arbor, MI


ATR-101 (Millendo Therapeutics, Inc., Ann Arbor, MI, USA) is an orally-administered adrenal-selective inhibitor of ACAT1 (acyl coenzyme A:cholesterol acyltransferase 1) in clinical development for the treatment of classic congenital adrenal hyperplasia (CAH), Cushing’s syndrome, and adrenocortical carcinoma. ACAT1 catalyzes cholesterol ester formation and, in the adrenal glands, is particularly important for creating a reservoir of substrate for steroidogenesis. In nonclinical studies, including a Cushing’s syndrome dog study, ATR-101 was shown to inhibit adrenal steroidogenesis.


Cushing’s syndrome results from the chronic effects of excessive glucocorticoids. Endogenous Cushing’s syndrome is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumors (i.e., Cushing’s disease), primary adrenal gland tumors, or ectopic (non-pituitary) ACTH-secreting tumors. Medical therapies for Cushing’s are generally used immediately prior to transsphenoidal surgery (for pituitary tumors) or following surgery if there is disease recurrence. Medical therapies can be broadly categorized as steroidogenesis inhibitors, cortisol receptor blockers or centrally-acting agents. In the United States (US), only mifepristone and pasireotide are labeled for the treatment of Cushing’s syndrome and Cushing’s disease, respectively; and both of these medications are limited to specific subsets of patients. Consequently, there is a need for additional medical therapies for Cushing’s syndrome.


ATR-101-301 is a Phase 2 randomized, double-blind, placebo-controlled clinical study that will be conducted at approximately 10 centers in the US and the United Kingdom (UK). Subjects with endogenous Cushing’s syndrome will first enter a 6-week open-label dose-titration period. All enrolled subjects will be started on ATR-101 250 mg orally BID. Every 14 days, the ATR-101 dose will be titrated to a maximum dose of 1000 mg BID as needed based on 24-h urinary free cortisol levels. After the open-label dose-titration period, responders will be randomized in a double-blind fashion either to continue their current dose of ATR-101 or be switched to a matching placebo for up to 4 weeks. The primary objective is to evaluate the efficacy and safety of ATR-101 in subjects with Cushing’s syndrome. Secondary objectives include changes in adrenal steroids and intermediates, and changes in ACTH. The study is open to adults with endogenous Cushing’s syndrome who are not considered to be surgical candidates and do not have cyclic Cushing’s syndrome. Approximately 16 subjects will be enrolled.


Disclosure: VHL: Employee, Millendo Therapeutics, Inc.. MI: Employee, Millendo Therapeutics, Inc.. MRP: Employee, Millendo Therapeutics, Inc.. PM: Employee, Millendo Therapeutics, Inc..