Imagine the possibilities. Unlike other drug candidates that have been tested, the compound being pursued by GTx is a hormonal agent. And the fledgling biotech says it has developed a once-daily pill that is reversible, according to findings presented at the American Association of Pharmaceutical Scientists last week, DrugResearcher reports.

Dubbed C-31, the pill is still about five years away from Phase I clinical trials, but the prospect may tantalize some whose alternatives are condoms, vasectomy and abstinence. The compound works, by the way, by using a selective androgen receptor modulator, or SARM, to suppress the luteinising hormone, which in turn, suppresses testosterone production. And as you know, a lack of testosterone stops the production of sperm.

A lot of hope has been pinned on testosterone or some other hormonal contraceptive with the aim of developing it in a pill form, DrugResearcher writes, but testosterone has so far proved unsuccessful in being formulated as an oral dosage form and can only be administered through a patch or injection. “People are using hormonal agents for contraception but it hasn’t been possible with an oral agent before. If you can do it orally, why wouldn’t you?” Jim Dalton, the biotech’s preclinical R&D vp tells DrugResearcher.

Animals were treated for three months with the oral formulation and found that sperm production was halted. When taken off the med, the researchers found the animals’ fertility returned after 100 days. “With women and birth control you want to stop fertility and know you can still have children (when you stop taking the birth control),” says Dalton. “It’s the same for men.”

The pill would take up to three months to take effect “just because sperm are in the testes that have to be depleted and that can take up to two to three months at least,” he explains, adding that it would take the same amount of time for fertility to return. Because of the length of time needed for effects to take place, there probably would not be a problem if the man missed taking a pill one day, Dalton says, adding that “men are probably safer (than women) in that regard… because it takes so long to start generating sperm again.”

Would men use a contraceptive pill? According to Dalton, the literature suggests men in their 20’s and 30’s would consider using a contraceptive so there was a potential market there. The problem is convincing drugmakers to develop the drug. Despite that, GTx entered into a more than $500m collaboration with Merck earlier this month to develop SARMs, DrugResearcher writes. The companies are combining research programs to develop GTx’ lead SARM candidate, which is in Phase II, for treating muscle loss in cancer patients.

Other non-hormonal candidates that have been investigated as male contraceptives include: the plant-derived compound gossypol, but there are questions about its reversibility; the Chinese herbal medicine Tripterygium wilfordii, which is used in the treatment of autoimmune diseases and has the known side effect of infertility but has other undesirable side effects; Nifedipine, a high blood pressure medication thought to have a contraceptive effect in some men which works by blocking the calcium channels in sperm membranes; Miglustat, approved under the brand name Zavesca in both the US and the EU for treatment of Gaucher Disease, interferes with sperm development and is reversible; a protein called CatSper that sperm need in order to beat their tails to move, but no drug has been developed to target the protein yet; sperm enzyme inhibitors; chloroform extract of Carica papaya seeds; oleanolic acid, a plant-derived substance found in cloves; and immunocontraceptives, which direct the immune system against cells in the reproductive system.

Source: DrugResearcher