We believe that a large number of men with testosterone deficiency remain untreated or do not adhere to their testosterone replacement therapy (TRT) because of dissatisfaction with currently available TRTs. For example, Schoenfeld et al. (J Sex Med 2013) reported that 60% of men discontinued topical gels within 1 year, after commencing therapy, based on a medical claims analysis of more than 15,000 hypogonadal men who were receiving testosterone gels.
We believe these low adherence rates result in part from inconvenient application and safety concerns about testosterone gels. Testosterone gels carry a "black box warning" because of their risk of transference of testosterone to children.
U.S. sales of TRTs were $1.4 Billion in 2018. Topical testosterone gels and testosterone solutions comprised 84% of these sales. There are several currently marketed non-oral TRTs to treat men with testosterone deficiency in the United States, including once-daily testosterone gels, testosterone injectables, once-daily testosterone patches, buccal patches and subcutaneous injectable pellets. We believe each of these existing therapies has limitations related to safety and ease of use.
- Testosterone gels and solutions: Testosterone gels and solutions are the most common topical formulations. Testosterone gels must be applied daily to broad sections of the upper arms, shoulders, stomach, or thighs. Testosterone solutions are applied daily to the axilla. Beyond the mess, inconvenience and potential skin irritation, testosterone gels carry the risk of inadvertent transference of testosterone to women and children from contact with the hands or other areas on which the gel has been applied which can be unsafe for the woman or child. Accidental exposure to testosterone via transference can cause premature puberty in children and changes in body hair or increased acne in women. The FDA requires a "black box warning" for these products due to the potentially severe consequences of testosterone transference to children. Despite these concerns, topical formulations accounted for 84% of the $1.4 billion total sales of TRTs in the United States in 2018, according to IMS Health.
- Testosterone injectables: Testosterone injections contain a testosterone prodrug, such as T-enanthate, or TE, or T-cypionate dissolved in oil, and are given intramuscularly every two to three weeks, typically into the muscle of the buttocks. A longer acting injectable formulation, Aveed®, uses TU as the prodrug in an oily vehicle. It is dosed intramuscularly every ten weeks and has an FDA Black Box warning related to the injection. Intramuscular injections of testosterone may be painful and generally require a visit to a physician's office for administration. Testosterone injections can also result in serum testosterone levels in excess of the upper limit of normal. Because men on this form of TRT are subject to wide-ranging levels of testosterone across the multi-week period between injections, they sometimes experience troublesome mood swings. A once-weekly subcutaneous injectable formulation of T-enanthate, Xyosted®, was recently approved by the FDA. Like JATENZO, this drug carries boxed warnings about BP elevations.
- Testosterone patches: These patches contain testosterone and are applied daily to different skin locations on the body. Common side effects associated with testosterone patches are itching, irritation or discomfort at the application site. Consequently, it is recommended that the patch not be applied to the same site more than once a week.
- Other Testosterone delivery methods: In addition to the delivery methods described above, a buccal patch, nasal gel, or subcutaneous injectable pellets are sometimes used in TRT. The buccal patch is a small, non-biodegradable patch that is placed twice daily onto a hypogonadal man's gums. Testosterone passes from the patch through the gums into the bloodstream. The primary problem with this route of TRT is that the patch does not always adhere properly and must be spit out if it becomes dislodged. When a patch is not in place, TRT is not active. A nasal gel product also has been approved for TRT. Its proper use requires dosing three times each day and treatment must be temporarily discontinued in the presence of severe rhinitis. Testosterone in the form of subcutaneously injectable pellets is also available. A surgical procedure is required for implantation.