BHR Pharma is developing BHR-200 (transdermal estradiol gel) for the palliative treatment of advanced androgen-sensitive carcinoma of the prostate. The investigational agent uses a proprietary transdermal estradiol formulation. It is targeted to be maintenance treatment in patients in whom so-called "androgen-deprivation therapy" or ADT has successfully lowered their circulating testosterone levels.
Virtually all prostate cancer is initially hormone-sensitive, meaning growth is promoted in the presence of androgens like testosterone and its more potent metabolite dihydrotestosterone.
The most common pharmacological treatment for prostate cancer is ADT, which aims to lower a patient's testosterone levels. The original non-surgical therapy to accomplish ADT involved the use of estrogens, specifically a synthetic estrogen called diethylstilbestrol or DES. DES works by inhibiting the release of gonadotropin-releasing hormone (GnRH) in the brain which blocks the gonadal production of testosterone and its metabolites.DES, however, became associated with a significant level of thromboembolic and other cardiovascular events. Today analogs of GnRH, like leuprolide and other GnRH agonists, are the standard of care for most prostate cancers.
But GnRH agonists deplete both testosterone and estrogen - testosterone's natural metabolite. Thus, they are associated with an increased risk of osteoporosis, obesity, altered lipid profiles, cardiovascular disease and cardiovascular death, symptoms of metabolic disorder like increased insulin resistance, and vasomotor symptoms like "hot flashes."
BHR-200 (transdermal estradiol gel) delivers the body's natural estrogen, estradiol, through transdermal application. Data suggest that by delivering estradiol transdermally, rather than orally, the thromboembolic events seen with earlier estrogen therapies will be substantially mitigated, and the use of estrogen should avoid the bone loss, hot flashes, and several other problems associated with the GnRH agonists.
BHR launched the Maintenance Suppression of Testosterone With Transdermal Estradiol (MASTERS) study in March 2015 to evaluate the safety and efficacy of three different doses of BHR-200 versus placebo for the maintenance of testosterone in men with advanced androgen-sensitive prostate cancer. The multi-center, randomized, double-blind, placebo-controlled, dose finding study will enroll approximately 120 men and is expected to be completed in October 2016.