Analgesic Efficacy of Fulranumab in Patients with Painful Diabetic Peripheral Neuropathy in a Randomized, Placebo-Controlled, Double-Blind Study (S58.002)

OBJECTIVE: To evaluate analgesic efficacy of fulranumab, a human recombinant investigational anti-nerve growth factor (NGF) monoclonal antibody, in patients with painful diabetic peripheral neuropathy (DPN). BACKGROUND: NGF antibodies offer a potential treatment option in DPN. DESIGN/METHODS: Multicenter, phase 2, placebo-controlled study (initiated Oct. 2009) with a 12-week double-blind (DB) efficacy-, 40-week DB safety extension-, and 52-week open-label safety extension phase. Patients with moderate to severe pain, stratified by concomitant treatment for neuropathic pain (yes/no), were randomized (3:2:2:3) to receive either placebo or fulranumab (1 mg-, 3 mg-, or 10 mg fulranumab; every 4 weeks [Q4wk] subcutaneously). RESULTS: Due to US FDA clinical hold, only 77 of planned 200 patients were enrolled: 62 (81%) patients (55.8% men; 81.8% white; mean [SD] age 58.7 [9.48] years) completed the DB efficacy phase. Change in 7-day average of daily pain intensity score from baseline to end of 12 week DB efficacy phase (primary endpoint) showed a positive dose response (p=0.014, one-sided). At DB efficacy endpoint, the pair-wise comparison between 10 mgQ4wk dose to placebo was significant (nominal p=0.04, two-sided). Least square (LS) means differences (95% CI) in change from baseline in average pain intensity scores vs placebo were: fulranumab 1mgQ4wk, 0.1 (-1.26; 1.36); 3mgQ4wk, -0.6 (-1.98; 0.74); and 10 mgQ4wk, -1.2 (-2.44; -0.06). 30% responder rates (≥30% improvement in average pain intensity score) at DB efficacy endpoint were: placebo, 21%; 1mgQ4wk, 44%; 3mgQ4wk, 43%; and 10 mgQ4wk, 61%. Multiple secondary efficacy endpoints showed dose-related improvement trends. Most common (≥5 patients) adverse events for total fulranumab-treated patients (n=53) vs placebo (n=24) were: peripheral oedema (11% vs 0%), arthralgia (11% vs 13%), and diarrhoea (9% vs 8%). No cases of joint replacement or deaths were reported during the study. CONCLUSIONS: Despite early study termination, fulranumab treatment resulted in dose-dependent efficacy and was generally well tolerated in this study. Supported by: Janssen Research & Development, LLC (previously known as Johnson & Johnson Pharmaceutical Research & Development, L.L.C), New Jersey, USA. Disclosure: Dr. Wang has received personal compensation for activities with Janssen Pharmaceutical as an employee. Dr. Wang has received (royalty or license fee or contractual rights) payments from Netrin3. Dr. Romano has received personal compensation for activities with Janssen Research & Development as an employee. Dr. Romano holds stock in Janssen Research & Development. Dr. Frustaci has received personal compensation for activities with Johnson & Johnson as an employee. Dr. Frustaci holds stock and/or stock options in Johnson & Johnson. Dr. Sanga has received personal compensation for activities with Janssen Research & Development as an employee. Dr. Ness has received personal compensation for activities with Janssen Research and Development LLC as an employee. Dr. Ness holds stock and/or stock options in Janssen Research and Development LLC. Dr. Russell has received personal compensation for activities with Janssen Pharmaceuticals as an employee. Dr. Russell holds stock and/or stock options in Janssen Pharmaceuticals. Dr. Fedgchin has received personal compensation for activities with Janssen Research & Development as an employee. Dr. Kelly has received personal compensatino for activities with Janssen Research and Development LLC as an employee. Dr. Kelly holds stock and/or stock options in Johnson & Johnson. Dr. Thipphawong has received personal compensation for activities with Janssen Pharmaceuticals as an employee. Dr. Thipphawong holds stock and/or stock options in Janssen Pharmaceuticals.