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FDA advisory panel split on safety of testosterone undecanoate
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The Reproductive Health Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee weighed in on the safety of testosterone undecanoate, which is indicated for replacement therapy in adult men with conditions associated with hypogonadism.
The committee was split in a 9-9 vote on whether testosterone undecanoate (Aveed, Endo Pharmaceuticals Solutions), an intramuscular injection, is safe for the proposed indication. In a 17-1 vote, panel members also decided that the applicant’s proposed instructions for use in the drug’s product labeling would not mitigate the risk for severe post-injection reactions. The labeling instructions state that testosterone undecanoate be administered using a slow (30- to 60-second) injection and that patients remain in the office for 30 minutes post-injection.
“There’s a real absence of data to prove that it’s truly safe. There are relative degrees of safety; we could try to improve on safety. However, I’m still a little concerned we don’t truly understand the mechanism of what’s happening, which is going to mean it’s going to be difficult to predict and prevent [severe post-injection reactions],” Lewis Nelson, MD, temporary voting member, and director of the Fellowship in Medical Toxicology at NYU School of Medicine, said after his vote against the safety of the drug. “We need better data to support the safety before I would be willing to say that it’s safe for broader use, especially once it comes out of clinical trials and into broader use in the US. I’m concerned that populations will change, the indications would broaden and the use would become more widespread than it already is, thus lowering the safety.”
Oil microembolism and other adverse events
Committee members focused on postmarketing reports of pulmonary oil microembolism (POME) in the lungs and potential anaphylactic reactions in patients administered the agent. Additionally, other testosterone injectable agents already approved by the FDA were referenced as they relate to oil microembolism and other adverse events.
Nelson and other voting members continuously cited a lack of comparative data, long-term cardiopulmonary consequences of the drug, and found difficulty justifying a recommendation based on the data presented throughout the entirety of the meeting.
During the public session portion of the meeting, The Endocrine Society representative, Allan R. Glass, MD, spoke regarding the use of injectable testosterone undecanoate as a treatment option for men with androgen deficiency.
“The [Endocrine] Society’s clinical practice guidelines on testosterone therapy in men with androgen deficiency syndromes, which was last updated in 2010 … indicated that in those countries where injectable testosterone undecanoate has been approved for use, it would be an acceptable option in the treatment of men with androgen deficiencies,” Glass said.
In a press release after the panel vote, The Endocrine Society encouraged the FDA to keep the risk-benefit profile (or lack thereof) in context for injectable testosterone undecanoate and its alternatives as the agency finalizes its deliberations between now and the anticipated Prescription Drug User Fee Act (PDUFA) date.
Moving Forward
Also in attendance during the meeting was Endocrine Today Editorial Board member Ronald Tamler, MD, PhD, MBA, clinical director of the Mount Sinai Diabetes Center, who spoke on behalf of the American Association of Clinical Endocrinologists.
Ronald Tamler
Although AACE does not advocate for approval of any specific drugs, Tamler said there is a need for new drugs to help manage the increasing burden and prevalence of male hypogonadism. After the meeting, Tamler spoke with Endocrine Today.
“It is something I see frequently in my practice: Patients are either on transdermal testosterone and worry about transmitting it to their loved ones, or they are on injectable testosterone and can choose between having unstable levels and having injections intramuscularly,” he said. “If proven safe, the medication can be a very valuable tool in the arsenal of treating hypogonadism. However, we have to be sure that it is a safe medication and we have to use it appropriately.”
If approved, the agency and sponsor agreed that a Risk Evaluation and Mitigation Strategy (REMS) would be required. This would include health care training, patient monitoring and labeling that would reflect the risk associated with the administration of testosterone undecanoate.
The PDUFA date is slated for mid-May. Although the FDA is not required to follow the recommendations of the advisory committee, it usually does. – by Samantha Costa
For more information:
Ronald Tamler, MD, can be reached at The Mount Sinai Diabetes Center, 10 E. 102 St., Fifth Floor, New York, NY 10029; email: ronald.tamler@mssm.edu.