Clarus Therapeutics has submitted to the FDA a testosterone replacement it claims overcomes the toxicity problems that have plagued other oral drugs like methyltestosterone.
Rextoro (formerly CLR-610) is absorbed via the intestinal lymphatic pathway, bypassing the liver. The makers predict oral delivery will make patients more compliant than with injectable testosterone or patches.
Less is more (testosterone)
Clarus CEO Bob Dudley told in-Pharmatechnologist.com Rextoro’s oral delivery of testosterone undecanoate also results in higher levels of free testosterone in the blood.
Testosterone undecanoate is a prodrug, meaning it is a medicine administered in less than fully active form, and is converted to its active form by the body.
“When you give our product orally, one of the effects is it decreases the synthesis of sex hormone binding globulin (SHBG) – that’s a key hormone and protein that binds testosterone in the blood,” said Dudley.
“98-99% of testosterone is bound either to SHBG or albumin, and only the free testosterone is what’s pharmaceutically active. Because we supressed SHBG we actually have higher levels of free testosterone.
“That’s unique to oral delivery. For a lower total testosterone amount, you have equivalent biological activity because you have higher free testosterone.”
$2 billion market and growing
Faisal Ghaus, VP at TechNavio Research, told in-Pharmatechnologist.com the global testosterone market was valued at over US$2bn in 2012 and is expected to grow at a compound annual growth rate of more than 20% over the next few years.
“One of the factors responsible for the growth of the market is the steadily growing aging population worldwide,” he said. “The normal production of testosterone is affected with age and low levels of testosterone result in issues such as low muscle strength, high adiposity, and high insulin resistance.
“Aggressive marketing campaigns by key market players have also contributed to the overall growth of the market.”
Testosterone: highs and lows
Ghaus expected Rextoro to be a convenient option for patients, with a significant advantage over alternatives currently on the market.
Clarus’s CEO echoed this view, saying the drug has “pretty significant breakout potential” because it overcomes the problems that cause low patient compliance with gels, patches and injections.
Gels run the risk of transferring to other people on skin-to-skin contact, leading the FDA to issue a black box warning in 2009 over harm to women and children.
“The patches are fairly irritating and the levels of testosterone are not great,” said Dudley.
“The injectables are painful, and if you do it every two weeks, you get highs and lows. Most men put off injecting, so they get high levels but then a see-saw effect.”
Rextoro capsules are administered twice a day, to avoid crashes. The FDA has set limits on how high a peak drugs can provoke.