This randomized, double-blind, Phase 3 study (56-week treatment; 24-week follow-up) assessed tanezumab in patients with chronic low back pain (CLBP) and history of inadequate response to standard-of-care analgesics (NCT02528253). Patients received placebo, subcutaneous tanezumab (5mg or 10mg every 8 weeks), or oral tramadol prolonged-release (100-300mg/day). Primary endpoint was change in Low Back Pain Intensity (LBPI) at week 16 for tanezumab versus placebo. Key secondary endpoints were proportion of patients with ≥50% decrease in LBPI at week 16, change in Roland Morris Disability Questionnaire (RMDQ) at week 16, and change in LBPI at week 2 for tanezumab versus placebo. Adverse events and joint safety were assessed through weeks 56 and 80, respectively. Tanezumab 10mg met the primary endpoint by significantly improving LBPI at week 16 versus placebo; least squares (LS) mean (95% CI) difference = -0.40 (-0.76, -0.04; P=0.0281). Tanezumab 10mg significantly improved all key secondary endpoints. Tanezumab 5mg did not meet the primary endpoint (LS mean [95% CI] treatment difference versus placebo = -0.30 [-0.66, 0.07; P=0.1117]), preventing formal testing of key secondary endpoints for this dose. The proportion of patients with ≥50% improvement in LBPI at week 16 was 37.4% in the placebo group, 43.3% in the tanezumab 5mg group (Odds ratio [95% CI] vs placebo = 1.28 [0.97, 1.70; P=0.0846]) and 46.3% in the tanezumab 10mg group (Odds ratio [95% CI] vs placebo = 1.45 [1.09, 1.91; P=0.0101]). Prespecified joint safety events were more frequent with tanezumab 10mg (2.6%) than tanezumab 5mg (1.0%), tramadol (0.2%), or placebo (0%). Seven patients, all in the tanezumab 10mg group (1.4%), underwent total joint replacement. In conclusion, tanezumab 10mg significantly improved pain and function versus placebo in patients with difficult-to-treat CLBP. Tanezumab was associated with a low rate of joint safety events, some requiring joint replacement. Sponsored by Pfizer Inc. and Eli Lilly & Company.

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