FDA Advisory Committee Meeting

HYATTSVILLE, MD.* – The majority of a Food and Drug Administration advisory panel recommended that the indication for testosterone replacement therapy should be revised to reflect the lack of efficacy data for age-related low testosterone and the possible increased cardiovascular risks associated with treatment.

At a meeting Sept. 17 the FDA’s Bone, Reproductive, and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 20-1 that the current indication, as worded in the labeling for all testosterone products, should be tightened to make it clear that testosterone therapy is not indicated for men with age-related reductions in testosterone. Other recommendations included adding diagnostic criteria to the indications section and specifying testosterone levels needed for a diagnosis of low testosterone. The meeting was held by the FDA to address whether the labeling for testosterone products reflects the appropriate indicated population for testosterone replacement therapy and to discuss the potential for adverse cardiovascular outcomes associated with this use.

The panel agreed there was a signal of a possible increased cardiovascular risk, which they described as “inconclusive” and “weak.” Several panelists noted that the risk was biologically plausible, adding that the label should include a statement with this information.

The majority of panelists (16) voted that the manufacturers of testosterone products should conduct randomized, controlled studies to evaluate the possible cardiovascular risks of testosterone therapy associated with certain indications. Four panelists voted that manufacturers should be required to conduct these studies regardless of the indication, largely because all testosterone products are being used off label for treating age-related low testosterone. Panelists pointed out that for the classic indications, such as primary hypogonadism, the benefit-risk profile of testosterone replacement therapy (TRT) was clear. Evidence that it is beneficial for treating older men with age-related low testosterone, however, was inconclusive, they noted.

“We don’t really know whether aging-associated low testosterone is in fact a disease at all,” said panelist Dr. A. Michael Lincoff, vice-chairman of cardiovascular medicine and professor of medicine at the Cleveland Clinic. Randomized controlled trials to “determine once and for all whether there really are benefits in this population are needed ... and whatever magnitude of efficacy is found, assuming efficacy is shown, will have to be balanced against safety,” he added.

The results of observational studies and meta-analyses have found mixed results regarding risk for cardiovascular adverse events associated with testosterone therapy, and the overall cardiovascular risks and benefits of testosterone therapy risks are unclear, according to the FDA.

According to national data presented by the FDA at the meeting, 2.3 million patients in 2013 received a prescription for testosterone, up from 1.3 million in 2010, and about 70% of the prescriptions are for men aged 40-64 years. The largest increase in prescriptions for TRT during 2010-2013 was in this age group, increasing from 850,000 to 1.5 million prescriptions. In a U.S. office-based survey of physicians, ”testicular hypofunction, not elsewhere classified” was the most common diagnosis for TRT use in men of all age groups.

The results of coordinated randomized, placebo-controlled studies on testosterone therapy in 800 elderly men with low testosterone are expected to be available by the summer of 2015. Outcomes will include physical, sexual, and cognitive function; vitality; and cardiovascular effects.

The FDA usually follows the recommendations of its advisory panels. In most cases, members of advisory panels have no financial conflicts, but in some cases, a panelist is granted waiver. At, this meeting, one panelist who owned stock in an affected company was granted a waiver.

emechcatie@frontlinemedcom.com

*Correction, 9/19/14: An earlier version of this article contained an incorrect dateline.

HYATTSVILLE, MD.* – The majority of a Food and Drug Administration advisory panel recommended that the indication for testosterone replacement therapy should be revised to reflect the lack of efficacy data for age-related low testosterone and the possible increased cardiovascular risks associated with treatment.

At a meeting Sept. 17 the FDA’s Bone, Reproductive, and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 20-1 that the current indication, as worded in the labeling for all testosterone products, should be tightened to make it clear that testosterone therapy is not indicated for men with age-related reductions in testosterone. Other recommendations included adding diagnostic criteria to the indications section and specifying testosterone levels needed for a diagnosis of low testosterone. The meeting was held by the FDA to address whether the labeling for testosterone products reflects the appropriate indicated population for testosterone replacement therapy and to discuss the potential for adverse cardiovascular outcomes associated with this use.

The panel agreed there was a signal of a possible increased cardiovascular risk, which they described as “inconclusive” and “weak.” Several panelists noted that the risk was biologically plausible, adding that the label should include a statement with this information.

The majority of panelists (16) voted that the manufacturers of testosterone products should conduct randomized, controlled studies to evaluate the possible cardiovascular risks of testosterone therapy associated with certain indications. Four panelists voted that manufacturers should be required to conduct these studies regardless of the indication, largely because all testosterone products are being used off label for treating age-related low testosterone. Panelists pointed out that for the classic indications, such as primary hypogonadism, the benefit-risk profile of testosterone replacement therapy (TRT) was clear. Evidence that it is beneficial for treating older men with age-related low testosterone, however, was inconclusive, they noted.

“We don’t really know whether aging-associated low testosterone is in fact a disease at all,” said panelist Dr. A. Michael Lincoff, vice-chairman of cardiovascular medicine and professor of medicine at the Cleveland Clinic. Randomized controlled trials to “determine once and for all whether there really are benefits in this population are needed ... and whatever magnitude of efficacy is found, assuming efficacy is shown, will have to be balanced against safety,” he added.

The results of observational studies and meta-analyses have found mixed results regarding risk for cardiovascular adverse events associated with testosterone therapy, and the overall cardiovascular risks and benefits of testosterone therapy risks are unclear, according to the FDA.

According to national data presented by the FDA at the meeting, 2.3 million patients in 2013 received a prescription for testosterone, up from 1.3 million in 2010, and about 70% of the prescriptions are for men aged 40-64 years. The largest increase in prescriptions for TRT during 2010-2013 was in this age group, increasing from 850,000 to 1.5 million prescriptions. In a U.S. office-based survey of physicians, ”testicular hypofunction, not elsewhere classified” was the most common diagnosis for TRT use in men of all age groups.

The results of coordinated randomized, placebo-controlled studies on testosterone therapy in 800 elderly men with low testosterone are expected to be available by the summer of 2015. Outcomes will include physical, sexual, and cognitive function; vitality; and cardiovascular effects.

The FDA usually follows the recommendations of its advisory panels. In most cases, members of advisory panels have no financial conflicts, but in some cases, a panelist is granted waiver. At, this meeting, one panelist who owned stock in an affected company was granted a waiver.

emechcatie@frontlinemedcom.com

*Correction, 9/19/14: An earlier version of this article contained an incorrect dateline.

HYATTSVILLE, MD.* – The majority of a Food and Drug Administration advisory panel recommended that the indication for testosterone replacement therapy should be revised to reflect the lack of efficacy data for age-related low testosterone and the possible increased cardiovascular risks associated with treatment.

At a meeting Sept. 17 the FDA’s Bone, Reproductive, and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 20-1 that the current indication, as worded in the labeling for all testosterone products, should be tightened to make it clear that testosterone therapy is not indicated for men with age-related reductions in testosterone. Other recommendations included adding diagnostic criteria to the indications section and specifying testosterone levels needed for a diagnosis of low testosterone. The meeting was held by the FDA to address whether the labeling for testosterone products reflects the appropriate indicated population for testosterone replacement therapy and to discuss the potential for adverse cardiovascular outcomes associated with this use.

The panel agreed there was a signal of a possible increased cardiovascular risk, which they described as “inconclusive” and “weak.” Several panelists noted that the risk was biologically plausible, adding that the label should include a statement with this information.

The majority of panelists (16) voted that the manufacturers of testosterone products should conduct randomized, controlled studies to evaluate the possible cardiovascular risks of testosterone therapy associated with certain indications. Four panelists voted that manufacturers should be required to conduct these studies regardless of the indication, largely because all testosterone products are being used off label for treating age-related low testosterone. Panelists pointed out that for the classic indications, such as primary hypogonadism, the benefit-risk profile of testosterone replacement therapy (TRT) was clear. Evidence that it is beneficial for treating older men with age-related low testosterone, however, was inconclusive, they noted.

“We don’t really know whether aging-associated low testosterone is in fact a disease at all,” said panelist Dr. A. Michael Lincoff, vice-chairman of cardiovascular medicine and professor of medicine at the Cleveland Clinic. Randomized controlled trials to “determine once and for all whether there really are benefits in this population are needed ... and whatever magnitude of efficacy is found, assuming efficacy is shown, will have to be balanced against safety,” he added.

The results of observational studies and meta-analyses have found mixed results regarding risk for cardiovascular adverse events associated with testosterone therapy, and the overall cardiovascular risks and benefits of testosterone therapy risks are unclear, according to the FDA.

According to national data presented by the FDA at the meeting, 2.3 million patients in 2013 received a prescription for testosterone, up from 1.3 million in 2010, and about 70% of the prescriptions are for men aged 40-64 years. The largest increase in prescriptions for TRT during 2010-2013 was in this age group, increasing from 850,000 to 1.5 million prescriptions. In a U.S. office-based survey of physicians, ”testicular hypofunction, not elsewhere classified” was the most common diagnosis for TRT use in men of all age groups.

The results of coordinated randomized, placebo-controlled studies on testosterone therapy in 800 elderly men with low testosterone are expected to be available by the summer of 2015. Outcomes will include physical, sexual, and cognitive function; vitality; and cardiovascular effects.

The FDA usually follows the recommendations of its advisory panels. In most cases, members of advisory panels have no financial conflicts, but in some cases, a panelist is granted waiver. At, this meeting, one panelist who owned stock in an affected company was granted a waiver.

emechcatie@frontlinemedcom.com

*Correction, 9/19/14: An earlier version of this article contained an incorrect dateline.