Leflutrozole (BGS-649) is a novel once weekly oral aromatase inhibitor that has completed a Phase 2b study in obesity-associated male hypogonadotropic hypogonadism (HH). The target indication is for treatment of HH-associated male infertility.
HH is a clinical syndrome that results from inadequate levels of testosterone. Symptoms that are most commonly associated with testosterone deficiency include reduced or loss of libido, the absence of morning erections and erectile dysfunction. Other common symptoms include fatigue, impaired physical endurance, loss of vitality, lack of motivation and mood disturbance. In the obese, the decrease in testosterone is driven by high levels of the aromatase enzyme in fat tissue which irreversibly converts testosterone into estradiol. BGS-649 normalizes testosterone levels by inhibiting aromatase and is therefore expected to improve the related conditions.
We have conducted a Phase 2b clinical trial of BGS-649 in 271 patients which met its primary endpoint demonstrating a normalization of total testosterone levels in over 75% of subjects after 24 weeks of treatment, and in at least 90% of patients after 24 weeks at the two highest doses. All three doses met all secondary endpoints, including the improvement of testosterone luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels. The exploratory endpoint of improvement in total motile sperm count was also met.
A safety extension study completed in 143 patients successfully demonstrated that none of the doses of BGS-649 met the lower bound (95% confidence interval) of the pre-specified safety criterion of a greater than 3% reduction in lumbar spine bone mineral density (BMD) after 48 weeks of treatment. The extension study also demonstrated normalization of testosterone in more than 90% of the patients at all three doses and maintenance of the effects on LH and FSH.
A total of 331 subjects in 9 clinical studies have received BGS-649, which was well tolerated.
Public presentations on BGS-649 (leflutrozole)
Beneficial Effect On Sperm Production of Leflutrozole in Men with Obesity-Associated Secondary Hypogonadotropic Hypogonadism: Results from a Phase II Study: ENDO 2019
- Based on 2016 WHO estimates
- Hofstra et al (2008) Netherlands J. Med, 66 p103-109
- Update on Hypogonadism and Testosterone Replacement Therapy (2011) Chapter in Practicing Clinical Exchange p1-15