Predictivity of Nonclinical Male Reproductive Findings for Human Effects

Area of Science:

• Pharmacology
• Toxicology
• Reproductive Medicine

Background:

• Regulatory agencies require testing of pharmaceutical products for male reproductive toxicity in laboratory animals.
• Nonclinical animal studies are a standard part of drug development and safety assessment.

Purpose of the Study:

• To evaluate the predictivity of male reproductive toxicity findings from animal studies for human clinical trial outcomes.
• To assess whether nonclinical male reproductive toxicity studies accurately forecast effects in men.

Main Methods:

• A survey of pharmaceutical companies was conducted to gather data on drug candidates.
• Data included nonclinical male reproductive toxicity findings and corresponding male reproductive effects observed in human clinical trials.

Main Results:

• Twelve pharmaceutical candidates from five companies were analyzed.
• Only one of the twelve compounds exhibiting male reproductive toxicity in animals also demonstrated such toxicity in men.

Conclusions:

• Nonclinical animal studies appear to over-predict male reproductive toxicity in humans.
• Further investigation is needed to understand the reasons for the observed lack of predictivity in experimental animal studies.