Could oral testosterone replacement therapy come in a capsule?

Clarus Therapeutics believes it has solved the oral availability problem for testosterone replacement therapy.

The firm says oral delivery of the product – used to treat low sex drive and hormone deficiencies – is highly sought-after because previous methods are unsafe, painful, or require surgery.

However, transporting an ingestible formulation of testosterone (T) through the gastrointestinal tract (GI) and liver to the intestinal lymphatic pathway has so far been too great a challenge.

Now using a softgel capsule specifically attracted to the lymph vessels in the intestine, named CLR-610, the team believe they have a viable solution. And following the success of its Phase III trial – carried out in conjunction with University of California and LA (UCLA) – Clarus thinks it could submit a new drug application (NDA) as soon as next year.

Speaking to in-PharmaTechnologist.com, Clarus president and CEO Robert Dudley said the market implications are huge with an “overwhelming” number of patients favouring the illusive oral option.

“According to IMS data, the T-replacement market was $1.7bn in the US in 2011,” he added. “A recent Global Industry Analysts report predicts the global T-replacement market will grow to $5bn by 2017. So clearly, the market is very large.”

Dudley was not prepared to give guidance for future sales of CLR-610, however he said that when considering the issues with other delivery methods, “we believe that an oral product would be very well accepted.”

How it works

CLR-610 is a softgel capsule of T prodrug and T undecanoate dissolved in excipients that are designed to foster absorption via the intestinal lymphatic pathway. 

Once absorbed, natural enzymes in the body cause T to be released from the prodrug. 

“By employing the prodrug, we were able to solve a major challenge that others trying to develop an oral T replacement have faced - that a large percentage of oral T is absorbed in the GI and liver, producing very low bioavailability,” said Dudley.

Other delivery mechanisms of testosterone have proved difficult for a variety of reasons.

The most popular formulation – T gels for topical application – has safety issues as patients have been found to inadvertently transfer the product to women and children, leading to premature puberty and changes in body hair. The US Food and Drug Administration (FDA) consequently issued a black box warning in 2009.

Clarus also told us injectable versions are painful and cause wide fluctuations in serum T levels, patches are an irritant and are under-effective, and T pellets require surgical implantation.

The study also found the capsule was more effective in raising serum T levels than a T gel comparator, with 87 per cent of the 141 men treated achieving average levels after 90 days. Of the 146 treated with gel, there was only an 80 per cent success rate.

“This is well above the 75 per cent suggested by current FDA guidance,” Dudley told us.