NGX-4010, a high-concentration capsaicin dermal patch for lasting relief of peripheral neuropathic pain

Abstract

NeurogesX Inc is developing NGX-4010, a rapid-delivery dermal patch application system that contains high-concentration trans-capsaicin, for the treatment of peripheral neuropathic pain. Capsaicin evokes a lasting and reversible refractory state in primary sensory neurons involved in the generation and maintenance of neuropathic pain. NGX-4010 can be applied to the painful skin area up to a total surface area of 1120 cm2. In phase I clinical trials, NGX-4010 increased the threshold for warmth detection, reduced epidermal sensory nerve fiber density and was well tolerated. In phase II trials, NGX-4010 was effective in reducing pain in patients with post-herpetic neuralgia (PHN), HIV-associated distal sensory neuropathy (HIV-DSP) and painful diabetic neuropathy (PDN). Data from phase III trials in patients with PHN demonstrated that significantly more pain relief was achieved by NGX-4010 (30 to 32% reduction from baseline) compared with a low-concentration capsaicin active control (20 to 24% reduction); however, only one of two studies involving patients with HIV-DSP met the primary endpoint. NGX-4010 appears to have the potential to be an effective adjunctive or a stand-alone therapy for PHN, as well as potentially for HIV-DSP and PDN. NGX-4010 has been granted approval by the European Commission and an NDA has been accepted for filing by the FDA.