FDA Rejects Capsaicin Patch for HIV-Related Neuropathy

On 9 February the Advisory Committee to the US FDA rejected by a vote of 12-0 an application for a capsaicin skin patch (NGX- 4010, Qutenza) for an indication of HIV-related pain based on proven efficacy. They also voted 11-0 that data the benefits did not outweigh the risks, with the community representative abstaining. [1]

The patch was approved by the FDA in November 2009 for post herpetic neuralgia (PHN) [2] and by the European Medicines Agency (EMA) in May 2009 for treatment of peripheral neuropathic pain in non-diabetic adults, either alone or in combination with other medicinal products for pain [3].

The active ingredient in the patch comes from hot chili peppers and it has been previously approved to relieve pain from shingles. The mechanism for reducing pain comes from a prolonged desensitisation to any local pain following this acute attack on the nerve in the damage area. Lidocaine cream is required to the affected area prior to the application to reduce pain from capsaicin.

The decision was based on 12-week results from two randomised, double-blinded, controlled phase III studies, in people with moderate to severe symptomatic HIV-related PN (total n~800), one of which has been published in JAIDS. [4]

Patients were randomised to either an 8% capsaicin patch, or a low-dose (0.04%) capsaicin control patch. The patches were applied for either 30, 60, or 90 minutes in one trial and either 30 or 60 minutes in the other trial.

The primary endpoint in both was a change in average pain for 24 hours.

The studies showed no relationship between dose or duration of exposure and impact on reducing pain. This may have been related to the study design where the control patch was designed to mimic the burning sensation of the active patch and use of other pain medication by participants.

There were no new safety concerns.

Comment

Because Qutenza has EU approval this decision by the FDA was reported to highlight the different interpretation of similar data.

A recent systematic review of randomised, controlled studies concluded that evidence of efficacy in the treatment of neuropathic pain associated with HIV-PN exists only for the Capsaicin 8% Patch, smoked cannabis, and subcutaneous recombinant human nerve growth factor (rhNGF). [5]

Up to four patches may be applied at one time, but this can only be repeated after 3 months.

References

1. FDA Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee. (9 February 2012)

   www.fda.gov/AdvisoryCommittees/Calendar/ucm283966.htm

2. FDA. FDA approves new drug treatment for long-term pain relief after shingles attacks. (17 November 2009).

   www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2009/ucm191003.htm

   FDA briefing document (186 pages -- PDF download) www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ AnestheticAndLifeSupportDrugsAdvisoryCommittee/UCM290279.pdf

3. EMA approval documents and SPC. (May 2009).

   www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000909/ human_med_001008.jsp&mid=WC0b01ac058001d124&murl=menus/medicines/medicines.jsp& jsenabled=true

4. Clifford DB et al. A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy. JAIDS. Volume 59 -- Issue 2 -- p 126–133, (1 February 2012).

   http://journals.lww.com/jaids/Abstract/2012/02010/ A_Randomized,_Double_Blind,_Controlled_Study_of.5.aspx

5. Phillips TJ et al. Pharmacological treatment of painful HIV associated sensory neuropathy: a systematic review and meta analysis of randomised controlled trials. PLoS One. 2010;5(12):e14433.

   http://clinicaltrials.ploshubs.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0014433

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