SILVER SPRING, MD. – A Food and Drug Administration advisory panel that met on Feb. 9 did not support approval of a capsaicin-containing transdermal patch as a treatment for pain associated with HIV neuropathy, because product studies had not provided adequate and compelling evidence of its efficacy for treating the condition.
At the meeting, the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee voted 12 to 0 that data from two studies of about 800 people did not provide "substantial evidence of effectiveness" of the 8% capsaicin patch for the management of neuropathic pain related to HIV-associated peripheral neuropathy. While panelists agreed that the risks associated with treatment were low, the panel also voted 11 to 0, with 1 abstention, that, based on the available data, the risk-benefit profile was not acceptable for approval.
Marketed as Qutenza by San Francisco–based NeurogesX, the 8% capsaicin patch was approved in the United States in November 2009 for the treatment of neuropathic pain associated with postherpetic neuralgia, and has been approved in the European Union for the treatment of peripheral neuropathic pain in nondiabetic adults.
The proposed new indication is for the use of the patch, applied for 30 minutes, for the management of neuropathic pain related to HIV-associated peripheral neuropathy. The patch is applied to the foot after a lidocaine cream is applied to the skin; it cannot be reapplied until at least 3 months later. The patch delivers capsaicin – the most abundant component of chili peppers – to the site of pain, where it desensitizes hyperactive nociceptors, according to the company.
Panelists expressed regret that they could not support expanded approval because of the unmet need for this type of treatment for these patients – and noted some evidence that it was effective in one of the two studies presented by the company. But they agreed that the evidence did not meet the FDA’s standards for approval.
Treatment with the 8% capsaicin patch was compared to a low-dose 0.04% capsaicin patch as the control in two 12-week randomized studies of mostly white, middle-aged men with documented HIV, who had experienced HIV peripheral neuropathy for at least 2 months, with moderate to severe pain. Almost 70% of the participants were on other analgesics at baseline, including opioids.
The primary outcome end point evaluating effectiveness was the percent change in the mean daily scores in a pain rating scale from 2 to 12 weeks after the patch was applied. In the first study, which compared the effects of the 8% capsaicin patch and the control patch applied for 30, 60, or 90 minutes, there was some evidence that the 8% patch was more effective than the control patch, but most of that evidence was from post hoc analyses. In the second study, which compared the 8% patch to the low-dose patch applied for 30 or 60 minutes, there were no statistically significant reductions in pain relief at 12 weeks, compared with the control patch.
Overall, the safety profile of the 8% patch in these trials was similar to that seen in patients with postherpetic neuralgia. The most common adverse events associated with treatment were application site reactions, affecting 76% of those who had the higher-dose patch and about 50% of those who had the low-dose control patch.
One of the panelists, Dr. Thomas Giordano, an HIV specialist at Baylor College of Medicine and medical director of HIV services, Harris County Hospital District, both in Houston, said it was difficult to vote against approval, because he believed that some of his patients could benefit from this treatment. But he added that he could not support approval because of the inconsistent results in the studies and the lack of an effect in the second study
Among the issues that complicated the study results was that the low-dose active control patch also appeared to provide some degree of pain relief. In addition, there was evidence that the 8% patch may have been more effective in patients who were not on an analgesic, according to the company.*
If approved, this would be the first product approved by the FDA for this indication, which affects about 40% of people with HIV, according to the FDA and the company. Approval is unlikely though, because the FDA usually follows the recommendations of its advisory panels.
The FDA’s deadline for a decision is March 7. The review is accelerated, and is being conducted within 6 months from the time of application. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.