



In discussions about contraceptives, historically the onus has fallen solely on females. While understandable to some degree, as women have a huge responsibility deciding which direction is appropriate for them, should an encounter “bear fruit.” Yet in recent years, much of the thinking about contraceptives has evolved, rightfully laying more responsibility at the feet of men. Now, a new study collaboration by investigators at UNC-Chapel Hill, Oregon Health and Sciences University (OHSU), and Eppin Pharma details how a compound called EP055 binds to sperm proteins to significantly slow the overall mobility of the sperm without affecting hormones, making EP055 a potential “male pill” without side effects.

Findings from the new study were published recently in PLOS ONE, in an article entitled “Inhibition of Sperm Motility in Male Macaques with EP055, a Potential Non-Hormonal Male Contraceptive.”

“Simply put, the compound turns off the sperm's ability to swim, significantly limiting fertilization capabilities,” explained lead study investigator Michael O'Rand, Ph.D., president/CEO of Eppin Pharma and a retired professor of cell biology and physiology at the University of North Carolina at Chapel Hill School of Medicine. “This makes EP055 an ideal candidate for nonhormonal male contraception.”

Currently, condoms and surgical vasectomy are the only safe forms of birth control currently available for men. However, there are hormonal drugs in clinical trials that target the production of sperm, but these affect the natural hormones in men much like female contraceptives affect hormones in women.

In the current study, the researchers showed that there was no indication of normal sperm motility 30 hours following a high-dose intravenous infusion of EP055 in male rhesus macaques. Furthermore, no physical side effects were observed.

“One particular target is the sperm EPPIN [epididymal protease inhibitor], which is present on the surface of human spermatozoa,” the authors wrote. “EP055 is a small organic compound that targets EPPIN on the surface of sperm and inhibits motility. EP055 was tested in cynomolgus (Macaca fascicularis) males to determine its plasma half-life after intravenous (i.v.) infusion of a single dose and for binding to its target tissues.”

“Our initial study demonstrated a plasma half-life for EP055 of 10.6 minutes. In a second study examination of macaque testis, epididymis, and plasma after i.v. infusion of a single dose of compound EP055 (63.25 mg/kg) demonstrated that EP055 was detected in testis and epididymis two hours and six hours post-infusion,” the authors added. “We initiated a trial in rhesus (Macaca mulatta) males to assess the availability of EP055 in semen and its effect on sperm motility as a measure of the drug's efficacy. Four macaques were infused with a low dose (75–80 mg/kg) followed by a recovery period and a subsequent high dose (125–130 mg/kg) of EP055. After high dose administration, sperm motility fell to approximately 20% of pretreatment levels within 6 hours post-infusion; no normal motility was observed at 30 hours post-infusion.”

Amazingly, the researchers saw that the monkeys showed no signs of side effects and their physiology reverted to its normal state.

“At 18 days post-infusion, all macaques showed signs of complete recovery, suggesting that the EP055 compound is indeed reversible,” stated co-senior study investigator Mary Zelinski, Ph.D., research associate professor at the Oregon National Primate Research Center at OHSU and associate professor of obstetrics and gynecology in the OHSU School of Medicine.

The scientists stressed that more work is needed before EP055 becomes available for human use, and that they have begun to test a pill form of the compound—eventually conducting a mating trial of EP055's effectiveness against pregnancy.



























