VERU-722 for the Treatment of Male Infertility

VERU-722

Scientific Overview

Up to 10% of infertile men have an endocrine cause and 2% of infertile men have an adult onset form of idiopathic hypogonadotropic hypogonadism. Current FDA-approved treatments for this indication include HCG and FSH injections. There are no FDA-approved oral therapies for male infertility. CLOMID (clomiphene citrate) 50 mg tablets are used off-label as first line empiric therapy in approximately two-thirds of idiopathic infertile men (Ko EY et al., J Urol 187:973-978, 2012). CLOMID is FDA-approved for the treatment of ovulatory dysfunction in women desiring pregnancy. CLOMID is a mixture of two geometric isomers cis-clomiphene (zuclomiphene) and trans-clomiphene (enclomiphene) containing between 30-50% of the cis-clomiphene isomer. Trans-clomiphene has antiestrogenic activity, while the cis-clomiphene has estrogenic activity. In men, clomiphene has the ability interact with the hypothalamus and pituitary gland to cause the secretion of LH, and the higher levels of LH will stimulate Leydig cells in the testes to produce testosterone, to promote spermatogenesis, and to improve sperm count and quality.

Based on the scientific literature, clomiphene has demonstrated the ability to improve sperm quality and sperm counts in infertile men and result in higher pregnancy rates. Based on 39 published studies, clomiphene appears to be well tolerated in men with doses as high as 400 mg/day and up to three years of use. However, the efficacy results for an individual patient have been inconsistent from study to study for several reasons: the form of clomiphene used contains varying ratios of the trans- and cis-clomiphene isomers, different doses were given, various dosing schedules were followed and different patient populations were studied. Clomiphene has not been formally studied for regulatory approval for the indication of male infertility; therefore, there is no established dose or schedule for efficacy or safety in men. VERU-722 is a patented, proprietary daily oral tablet that has a specific fixed ratio of the combination of trans- and cis-clomiphene isomers.

VERU-722

Development Plan

VERU-722 is being developed as the first oral agent for the treatment of male infertility. VERU-722 has fixed ratio of the combination of trans- and cis- clomiphene isomers. Using a fixed ratio approach will allow the determination of the correct dose and schedule for efficacy and safety for the treatment of male infertility. The patient population will be men who have hypogonadotropic hypogonadism and infertility. Veru met with the FDA for a pre-IND meeting where the FDA confirmed that VERU-722 qualifies for the 505(b)(2) regulatory pathway. The formulation, doses and dosing regimen for VERU-722 will differ from those of CLOMID. Despite the differences, the approval of VERU-722 will rely on nonclinical and clinical efficacy and safety information from the listed drug labeling and in the published literature.

VERU-722

Market

If approved, VERU-722 will be indicated as the first oral treatment for male infertility. Infertility affects 6.1 million couples in the United States representing 15% of all couples trying to conceive. Up to 50% of infertility is attributed to males who are subsequently found to have abnormal semen analysis, of which 50% of these men are diagnosed with idiopathic, or unexplained, infertility. Two-thirds of men with idiopathic male infertility are empirically treated with off-label use of CLOMID. VERU-722 may be effective in treating cases of male factor infertility that arise from idiopathic infertility, including those with hypogonadotropic hypogonadism. The current U.S. market size for idiopathic male infertility is estimated to be $700 million annually per IMS.