Fulranumab in Patients With Pain Associated With Postherpetic Neuralgia and Postraumatic Neuropathy Efficacy, Safety, and Tolerability Results From a Randomized, Double-blind, Placebo-controlled, Phase-2 Study

Objective: Fulranumab is an antibody that specifically neutralizes the biological activity of human nerve growth factor. This multicenter, phase-2, randomized, double-blind (DB), placebo-controlled study evaluated the analgesic efficacy and safety of fulranumab in postherpetic neuralgia (PHN) and posttraumatic neuropathy (PTN) patients. Methods: Patients (18 to 80 y) with inadequately controlled moderate-to-severe pain received study medication (subcutaneous injection) every 4 weeks. PHN patients were randomized (3: 2: 2: 3) to receive either placebo or one of 3 doses of fulranumab: 1mg (1 mgQ4wk), 3mg (3 mgQ4wk), or 10 mg (10mgQ4wk). PTN patients were randomized (1: 1) to receive either placebo or fulranumab 10mgQ4wk. Results: The US Food and Drug Administration placed a clinical hold (December 23, 2010) on all trials of antinerve growth factor drugs, including fulranumab, due to identified risks of osteonecrosis or rapidly progressing osteoarthritis; therefore, only 49 (of 150 planned) PHN patients and 34 (of 50 planned) PTN patients completed the DB efficacy evaluation. There was no significant difference (P > 0.05, fulranumab vs. placebo) for change in 7-day average of daily pain intensity scores from DB baseline to end of 12-week DB efficacy phase in PHN or PTN patients (primary endpoint). No significant difference was found with fulranumab versus placebo (P> 0.05) in other efficacy measures in either PHN or PTN patients. The most common treatment-emergent adverse events (> 10% incidence) in PTN patients were sinusitis, carpal tunnel syndrome, and headache, whereas in PHN patients it was arthralgia. Discussion: Fulranumab did not demonstrate efficacy in either PHN or PTN patients, but was generally well-tolerated in this small underpowered and abbreviated study.