One approach to oral androgen delivery is to chemically modify testosterone in a way that makes it resistant to metabolism by the liver. This method was used more than 40 years ago when methyl-testosterone was developed. However, methyl-testosterone has been associated with potentially serious liver toxicity and, although it is approved in the United States, it is rarely prescribed as a result. Some countries, such as Germany, have banned its use.
Another oral testosterone delivery approach, originally developed in the 1970s, was to create orally active testosterone prodrugs by combining testosterone and fat-like molecules to create a T-ester. A testosterone prodrug is an inactive version of testosterone that is converted by endogenous enzymes in the body to testosterone (active form). While testosterone prodrugs sufficiently avoid first-pass liver metabolism, there have been a number of challenges related to the clinical use of these early formulations, including inconsistent absorption into the lymphatic system, insolubility issues and the influence of fat content in food, all of which can lead to variable testosterone levels. These issues often create unpredictable clinical responses and poor efficacy. For example, we believe that these limitations have negatively affected the clinical and commercial success of Andriol®, an oral testosterone undecanoate product marketed outside the United States by Merck & Co., Inc. since the early 1970s. The published literature indicates that average serum testosterone levels in response to Andriol are highly variable and that Andriol often yields an inadequate clinical response.
Our founder, President and Chief Executive Officer, Dr. Robert E. Dudley led the discovery, development, regulatory approval and launch of AndroGel 1%, the first testosterone gel product. Dr. Dudley, our management team and investors founded Clarus Therapeutics with the goal of developing an oral testosterone product to expand patient choice in a market currently dominated by non-oral options. We believe that current users of testosterone products desire an oral testosterone option that is safe and effective. We believe that the ultimate result of these pursuits, JATENZO, overcomes a number of the problems associated with earlier attempts to formulate and deliver oral testosterone for therapeutic treatment. JATENZO is the first-in-class FDA-approved oral formulation of a testosterone prodrug in the United States to treat hypogonadism.
Specific JATENZO formulation attributes include:
The active component of JATENZO is a testosterone prodrug formed by the combination of testosterone with a fat-like molecule, or fatty acid, to create the T-ester TU. JATENZO is a proprietary formulation (issued U.S. and foreign patents) of TU using a liquid, self-emulsifying drug delivery system, or SEDDS, in a softgel capsule. In the presence of the water naturally present in the stomach and small intestine, this formulation maintains the TU in solution so that the body can form lipoprotein particles containing TU that are preferentially absorbed through the intestinal lymphatic system, thus bypassing delivery to the liver. Once TU enters the circulation by this pathway, it is acted upon by endogenous enzymes throughout the course of the day to cleave off the fatty acid, yielding circulating testosterone. The liberated fat-like molecule is metabolized like any other fatty acid present in food.
JATENZO will be administered twice-daily with food. Patients taking JATENZO will visit their physician's office one or two times after commencing JATENZO therapy to measure their serum testosterone levels and potentially have their JATENZO dose adjusted, similar to the dose adjustment regimen used in connection with testosterone gels and other testosterone replacement therapies (TRT).
We believe JATENZO will offer hypogonadal men and prescribing physicians a safe and effective oral TRT option and will have a number of advantages over the currently approved TRTs, including: