FDA Advisory Panels Reject Testosterone Replacement Therapy

September 25, 2014

Two FDA advisory panels have overwhelmingly recommended the agency not approve Clarus Therapeutics’ Rextoro testosterone replacement therapy.

In an 18-3 vote last week, members of the agency’s Bone, Reproductive and Urologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee said the benefit-risk profile on Rextoro (testosterone undecanoate) was not sufficient to support approval. The joint committee also voted 12 to 8 that there was not sufficient evidence to say the product is even effective.

Clarus had argued that the drug restored testosterone to normal levels in at least 75 percent of patients in Phase III trials, and that its oral formulation is more convenient than other therapies, which will lead to greater adherence.

The company said Sept. 19 that it would work closely with the FDA to resolve the panel’s concerns. The FDA is not required to follow its advisory panel recommendations, but generally does.

Meanwhile, manufacturers of all testosterone-replacement therapies (TRTs) may soon have to change their labeling if the FDA heeds advice of panelists at a separate, related meeting.

TRTs such as Abbott Laboratories’ AndroGel (testosterone gel) are currently indicated for men with a deficiency caused by congenital or acquired hypogonadism. On Wednesday, members of the same committee voted 20 to 1 that TRTs’ labeling should specifically indicate men with valid medical conditions that cause dysfunction of the testes, rather than men who experience normal age-related decreases in testosterone levels.

The numbers of men who are prescribed these drugs has been growing in recent years, from 1.3 million in 2010 to 2.3 million in 2013, according to FDA statistics.

There is no solid evidence that age-related hypogonadism exists or that TRTs are helping patients who take them for this purpose, said Public Citizen’s Michael Carome, who offered testimony at the meeting. About 50 percent of men stop taking the therapy after three or four months, according to industry and FDA data. Carome said that this suggests the products are not particularly effective.

TRTs also may be associated with a greater risk of heart attacks and strokes. The FDA began investigating this link in 2010 after one trial showed an increase in heart problems in men treated with TRTs. The vast majority of advisors recommended manufacturers include some kind of warning about cardiovascular risks, with some calling for a black box warning and others simply saying there should be some kind of statement that the two might be connected.

The FDA rejected a citizen petition brought by Public Citizen just two months ago that requested the agency approve the same warning. — Lena Freund

Originally appeared in Drug Industry Daily, the pharmaceutical industry’s number one source for regulatory news and information. Click here for more information.