In the briefing package, submitted along with the protocols, the Company also presented data to support both 12.5 and 25 mg doses as suitable for Phase III testing. In September of 2004 the Company held an “end of Phase II” meeting with the FDA during which Repros presented data supporting the selection of the two doses for a study designed to assess the ability of Androxal to normalize morning testosterone in men with secondary hypogonadism. The FDA took no issue with the dose selection but opined that testosterone as an endpoint was not suitable for a drug such as Androxal and that the Company would need to determine an additional clinically relevant outcome. Male fertility is clinically relevant. In general, men with secondary hypogonadism are fertile. It is the treatment with exogenous testosterone that induces an infertile state due to suppression of important reproduction related pituitary hormones. Therefore, in the case of Androxal, dose selection is based on the ability of the oral drug to normalize testosterone.
As part of the meeting the Company has asked if the Agency will be willing to review the two pivotal protocols under a Special Protocol Assessment (SPA). The Company expects the FDA will likely request modifications to the two protocols before and if agreeing to SPA review.
It should be noted that even though Androxal may be proceeding to pivotal Phase III studies, the FDA will be reviewing the drug as a New Chemical Entity and as such Repros will be required to conduct large open label safety studies (100 subjects for a year and 300-600 subjects for six months) as well as special population and drug-drug interaction studies amongst others before a new drug application can be submitted. Over 50 men have taken Androxal for over a year and over 100 men have been administered the drug for longer than 6 months. In all previous studies Androxal has been generally well tolerated.