One approach to oral androgen delivery is to chemically modify T in a way that makes it resistant to metabolism by the liver. This method was used more than 40 years ago when methyl-T was developed. However, methyl-T 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 T delivery approach, originally developed in the 1970s, was to create orally active T prodrugs by combining T and fat-like molecules to create a T-ester. A T prodrug is an inactive version of T that is converted by natural enzymes in the body to T. While T 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 T levels. These issues often create unpredictable clinical responses and poor efficacy. Finally, even when target T levels are achieved, T is rapidly cleared by the body once it reaches the bloodstream, thus requiring either frequent dosing or high and unsafe levels of T in order to maintain the desired therapeutic effect throughout the day. For example, we believe that these limitations have negatively affected the clinical and commercial success of Andriol®, an oral T undecanoate product marketed outside the United States by Merck & Co., Inc. since the early 1970s. The published literature indicates that average serum T 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, the first T gel product. Dr. Dudley, our management team and investors founded Clarus Therapeutics with the goal of successfully commercializing an oral T product to expand patient choice in a market currently dominated by non-oral options. We believe that current users of T products desire an oral T option that is safe and effective.
In pursuit of our goal, we explored a wide array of proprietary combinations of T prodrugs and excipients to achieve optimal formulation characteristics. 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 T for therapeutic treatment. JATENZO, once FDA approved, will be a first-in-class oral formulation of a T prodrug in the United States to treat hypogonadism.
Specific JATENZO formulation attributes include:
The active component of JATENZO is a T prodrug formed by the combination of T 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 normally existing natural enzymes throughout the course of the day to cleave off the fatty acid, yielding circulating T. The liberated fat-like molecule is metabolized like any other fatty acid present in food.
JATENZO will be administered twice-daily, which we believe is a safe way to achieve clinical efficacy while avoiding concerns about peak serum T levels. Patients taking JATENZO will visit their physician's office one or two times after commencing JATENZO therapy to measure their serum T levels and potentially have their JATENZO dose adjusted, similar to the dose adjustment regimen used in connection with T gels and other T-replacement therapies.
We believe JATENZO, once approved, will offer hypogonadal men and prescribing physicians a safe and effective oral T-replacement option and will have a number of advantages over the currently approved T-replacement therapies, including: