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Background Analysis: US FDA Advisory Committee to Discuss the Development of Testosterone Replacement Therapy for Adolescent Males with Classical Hypogonadism – APR 8, 2019 (PEDAC)


The US FDA has scheduled a Pediatric Advisory Committee (PEDAC) meeting for Monday, April 8, 2019 to discuss drug development of testosterone replacement therapy in male adolescents with classic hypogonadism.

Indication Background

Testosterone is a hormone that is crucial for the growth and development of the male sex organs and for the maintenance of secondary sex characteristics. Testosterone levels begin declining naturally at the age of 30 years. Yet there can also be other causes for testosterone to decline, including the following: (1) injury, infection, or loss of the testicles; (2) radiation or chemotherapy treatment for cancer; (3) genetic abnormalities such as Klinefelter's Syndrome (extra X chromosome); (4) hemochromatosis (too much iron in the body); (5) dysfunction of the pituitary gland; (6) inflammatory diseases such as sarcoidosis (a condition that causes inflammation of the lungs); (7) medications, especially hormones used to treat prostate cancer and corticosteroid drugs; (8) chronic illness; (9) chronic kidney failure; (10) liver cirrhosis; (11) stress; (12) alcoholism; and (13) obesity (especially abdominal).

When endogenous testosterone is deficient or absent due to structural or genetic etiologies, it is referred to as classic hypogonadism.

Product Background

FDA-Approved Testosterone Replacement Therapies

As the name implies. testosterone replacement therapies (TRTs) are designed to replace testosterone in men who lack or have low testosterone levels. US FDA-approved TRTs are indicated only for men who lack or have low testosterone levels based on a reliable test and who have an associated medical condition. They are not approved for age-related testosterone decline. Various routes of administration have been FDA-approved, including the following: oral (Android, Testred); intramuscular injection (Depo-Testosterone, Aveed); subcutaneous injection (Testopel, Xyosted); mouth patch (Striant); body patch (Androderm, Testoderm); topical solution (Axiron); topical gel (AndroGel, Axiron, Fortesta, Testim, Vogelxo); and intranasal gel (Natesto). These contain testosterone in various forms, including plain testosterone, methyltestosterone, testosterone undecanoate, testosterone enanthate, and testosterone cypionate.

Safety Considerations

TRTs are associated with possible increased risk of heart attack and stroke. On March 3, 2015, the FDA issued a Safety Announcement on this topic. Along with the announcement, the Agency required labeling changes for all prescription testosterone products. They also required manufacturers of approved testosterone products to conduct a clinical trial to more clearly address the question of whether an increased risk of heart attack or stroke exists among users of these products. The FDA encouraged manufacturers to work together on a clinical trial, but they also allowed them to work separately if they chose to.

TRTs are also associated with a risk of abuse and dependence. On October 25, 2016, the FDA issued a Safety Announcement and required labeling changes for all prescription testosterone products regarding the abuse potential of testosterone and serious adverse outcomes, especially those related to the heart and mental health, that have been reported in association with testosterone and other anabolic androgenic steroids (AAS). The announcement noted that testosterone and other AAS are being abused by adults and adolescents, including athletes and body builders.


The committee will discuss drug development of TRT in male adolescents with classic hypogonadism. The following topics will be considered for discussion: diagnosing male adolescents with classic hypogonadism; evidence to establish efficacy and safety of testosterone replacement therapy in this population; study design; and feasibility considerations for such studies. The committee will not discuss any individual research programs.

What’s Next?

Tarius will send a Briefing Summary after briefing materials are posted to FDA’s website (typically within 2 days of the meeting). This report will provide a summary of the FDA and the Sponsor’s briefing materials.

Tarius will send a Results Wire soon after the meeting. This report will include the voting outcomes, if applicable, and key outcomes of the discussion.

METADATA: Sponsor: none Drug Name: none Drug Class: hormone Indication: testosterone replacement therapy

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DISCLAIMER: The information in this document is for informational purposes only. The SAC Tracker Background Analysis contains information from publicly available sources, including FDA, sponsor, scientific, and clinical websites. Tarius A/S assumes no liability for any inaccurate or incomplete information, or for any actions taken in reliance thereon. © Tarius A/S. All rights reserved.