NeurogesX Inc (fka NGSX)

[bob smith]

briefing docs:

initial review does not look good, as thus the the pre market activity.

setback, but lets see how this develops:

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AnestheticAndLifeSupportDrugsAdvisoryCommittee/UCM290278.pdf

The indication that the Applicant is seeking, pain associated with HIV-PN, is a serious condition affecting approximately 40% of HIV patients. There are no FDA-approved therapies for this indication. Therefore, there is a medical need for an effective therapy.
Two efficacy studies were submitted to support the efficacy of Qutenza®; neither achieved their objective for the pre-specified primary efficacy analysis. Specifically, Study C107 failed to demonstrate superiority for the 60-minute Qutenza® application compared to low-dose capsaicin controls. The 30-minute application was superior to the total control treatment arm (i.e., control 30-, 60-, and 90-minute applications) and the control 30-minute application treatment arm. These efficacy results were not sensitive to missing value imputation or sensitivity analyses (i.e., the landmark analyses, with and without covariates). Further, secondary endpoints were in favor of the 30-minute Qutenza® patch application.
Study C119 also failed on its pre-specified primary analysis, possibly due to a better low-dose capsaicin control response, failure to adjust for covariates and potential outliers. Post-hoc analyses (adjusting for additional covariates, removing a potential outlier, and non-parametric analyses) provided supportive evidence.
The safety profile was comparable to what was reported in the PHN clinical development program. In general, Qutenza® 30-minute applications were associated with less pain, lower increases in blood pressure, less dermal irritation, and less medication use for treatment-related discomfort compared with longer (i.e., 60- or 90-minute) application durations.
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Background Material - sNDA 22395/S-013
Qutenza® for the Management of Neuropathic Pain Associated with HIV-PN
7 Draft Topics for Discussion
1.
Considering that a dose-response was not observed in Study C107 and that the efficacy results of the 60-minute and 30-minute applications of Qutenza® failed to achieve statistical significance based on the pre-specified hierarchical testing procedure, has the efficacy of the 30-minute application of Qutenza® been demonstrated for the management of neuropathic pain associated with HIV-PN?
2.
Considering that Study C119 failed to achieve statistical significance for the primary efficacy outcome based on the pre-specified analysis, do the results of this study support the efficacy of the 30-minute application of Qutenza® for the management of neuropathic pain associated with HIV-PN?
3.
Do the data from the two clinical trials, C107 and C119, provide substantial evidence of effectiveness of Qutenza® for the management of neuropathic pain associated with HIV-PN?
4.
If the answer to Question #3 above is no, what additional studies or data are needed, e.g., dose ranging studies and/or additional efficacy trials?
5.
Has the Applicant submitted sufficient safety data to assess the safety profile of Qutenza® in the intended patient population?
6.
If you have determined that there is substantial evidence to support the effectiveness of Qutenza® for the management of neuropathic pain associated with HIV-PN, is the risk-benefit profile acceptable for Qutenza® to be approved for this indication?
51
Background Material - sNDA 22395/S-013
Qutenza® for the Management of Neuropathic Pain Associated with HIV-PN

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