A Comprehensive Monograph on the Investigational GnRH Antagonist: Acyline (DB11906)

1.0 Executive Summary

Acyline (developmental code name MER-104) is a potent, long-acting, synthetic peptide classified as a third-generation gonadotropin-releasing hormone (GnRH) antagonist.[1] As a small molecule oligopeptide, its primary mechanism of action is the direct, competitive inhibition of the gonadotropin-releasing hormone receptor (GnRHR) located on the anterior pituitary gland.[4] This blockade prevents endogenous GnRH from stimulating the receptor, resulting in an immediate, profound, and sustained suppression of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH).[6] The subsequent reduction in gonadotropin signaling leads to a rapid decrease in gonadal steroidogenesis, most notably causing serum testosterone levels in males to fall to castrate levels without the initial "flare" effect characteristic of GnRH agonists.[5]

The clinical development program for Acyline was ambitious, with male hormonal contraception as its lead indication, reaching Phase 3 clinical trials.[2] Its potent and long-lasting effect, with a single subcutaneous injection capable of suppressing testosterone for over two weeks, made it a promising candidate for a convenient, long-acting male contraceptive regimen.[7] The compound was also explored in Phase 2 trials for a range of other hormone-dependent conditions, including advanced prostate cancer, androgen deficiency, precocious puberty, and metabolic disorders such as Type 2 diabetes mellitus and obesity.[2]