Subcutaneous Tanezumab Versus Placebo or Tramadol in Patients with Chronic Low Back Pain: 16- Week Efficacy and Safety Results from a Phase 3 Study (305)

Objective: Assess efficacy and safety of tanezumab in patients with chronic low back pain (CLBP) and history of inadequate response or intolerance to standard-of-care analgesics. Background: Tanezumab, a monoclonal antibody against nerve growth factor, is in development for treatment of chronic pain. Design/Methods: In this randomized double-blind trial, patients received placebo (N=409), subcutaneous tanezumab (5mg [N=407] or 10mg [N=407] every 8 weeks), or oral tramadol prolonged-release (100–300mg/day; N=602). Efficacy (Low Back Pain Intensity [LBPI] and Roland Morris Disability Questionnaire [RMDQ]) was assessed through week 56. Safety, including joint safety, was assessed through week 80. Week 16 data is presented here; week 56 data is presented in our companion abstract. Results: Compared with placebo, tanezumab 10mg significantly improved LBPI (primary endpoint; LS mean [95% CI] difference = −0.40 [−0.76,−0.04]; p=0.0281) and RMDQ (key secondary; LS mean [95% CI] difference = −1.74 [−2.64,−0.83]; p=0.0002) at week 16. Changes in LBPI with tanezumab 5mg were not significant versus placebo (LS mean [95% CI] difference = −0.30 [−0.66,0.07]; p=0.1117). Although mean changes in RMDQ were larger with tanezumab 5mg than placebo (LS mean [95% CI] difference = −1.32 [−2.21,−0.43]; p=0.0035), superiority could not be concluded per the pre-defined testing strategy. Changes in LBPI and RMDQ with tramadol (mean dose=203mg/day) were not significant versus placebo. Changes in LBPI for both tanezumab groups were not significant versus tramadol. Both tanezumab groups significantly improved RMDQ compared with tramadol (unadjusted for multiplicity). Adverse event rates through 16 weeks were 46.2%, 46.9%, 51.8%, and 56.3% in the placebo, tanezumab 5mg, tanezumab 10mg, and tramadol groups, resulting in treatment discontinuation rates of 3.9%, 4.4%, 4.7%, and 8.5%. Conclusions: Tanezumab 10mg significantly improved pain and function at week 16 versus placebo, while tramadol did not. Incidence of AEs and treatment discontinuations due to AEs in both tanezumab groups were lower than tramadol, but higher than placebo. Disclosure: Dr. Markman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Esteve, Averitas, Sophren, Flexion Therapeutics, Tremeau Pharmaceuticals, Eliem Therapeutics, Vertiflex, Pfizer, Lilly, Quark, Novartis, Merck, Editas Medicine. Dr. Markman has received compensation for serving on the Board of Directors of Yellowblack Corporation. Dr. Markman has received research support from Pfizer. Dr. Bolash has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with TerCera, Medtronic, Abbott, Pfizer, and Nuvectra. Dr. Bolash has received research support from Pfizer, Nuvectra, Stimwave, and Boston Scientific.Dr. McAlindon has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer; Sanofi Aventis US; Kolon Tissuegene; Samumed; Seikagaku; Kiniksa Pharmaceuticals; Anika Therapeutics. Dr. Kivitz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celegene, Horizon, Merck, Novartis, Pfizer, Genzyme, Sanofi, Regeneron, Abbvie, Flexion: all speaking and teaching; Abbvie, Janssen, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Boehringer Ingelheim:all Advisory committe; Pfizer, Sanofi, Regeneron, Sun Pharma. Dr. Pombo-Suarez has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Janssen and Janssen; Lilly; MSD; Sanofi; UCB.. Dr. Ohtori has received research support from Asahi Kasei Pharma Corporation; AYUMI Pharmaceutical Corporation; Eisai Co., Ltd.; Kaken Pharmaceutical Co.,Ltd.; Johnson & Johnson K.K.; Nippon Zoki Pharmaceutical Co., Ltd.; Hisamitsu Pharmaceutical Co.,Inc.; Astellas Pharma Inc.; Daiichi Sankyo Co., Lt. Dr. Li has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer Inc, Eisai Inc: Employment. Dr. Li holds stock and/or stock options in Pfizer: As part of employment which sponsored research in which Dr. Li was involved as an investigator. Dr. Viktrup has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly: Employment. Dr. Viktrup holds stock and/or stock options in Eli Lilly: As part of employment which sponsored research in which Dr. Viktrup was involved as an investigator. Dr. Viktrup holds stock and/or stock options in Eli Lilly: As part of employment. Dr. Bramson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer Inc. Dr. Bramson holds stock and/or stock options in Pfizer which sponsored research in which Dr. Bramson was involved as an investigator. Dr. West has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer: Employment. Dr. West holds stock and/or stock options in Pfizer: As part of employment which sponsored research in which Dr. West was involved as an investigator. Dr. Verburg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Inc. Dr. Verburg has received compensation for serving on the Board of Directors of Pfizer, Inc. Dr. Verburg holds stock and/or stock options in Pfizer, Inc which sponsored research in which Dr. Verburg was involved as an investigator.