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The objective of this study was to compare the analgesic efficacy of tanezumab versus placebo in patients with osteoarthritis (OA) of the knee. This was a 32-week, randomized, double-blind, placebo-controlled phase III trial (NCT00733902). The patient criteria included diagnosis of OA; Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscale scores of ≥5 and ≥4, respectively; Patient's Global Assessment of Osteoarthritis (PGA) ≥3; and failure of nonopiate pain medications or candidacy for invasive interventions. Patients received 3 intravenous doses of tanezumab (2.5, 5, or 10 mg) or placebo. The co-primary efficacy end points were changes in WOMAC subscales and PGA at week 16. Adverse events were monitored throughout. Overall, 690 patients (61% female) were randomized and treated. Those treated with tanezumab showed significant improvement in the 3 co-primary end points ( P ≤ .015 for all). The incidence of adverse events was 55 to 60% for tanezumab-treated patients versus 48% for placebo-treated patients. Joint replacement was reported in 4 patients, 1 in each treatment group; a total of 5 joints were replaced (1 index knee and 4 hips). The tanezumab OA clinical program is currently on clinical hold due to potential adverse reactions leading to joint replacement. Perspective This is the first phase III randomized, controlled trial to demonstrate that nerve growth factor blockade by tanezumab has superior analgesic efficacy in OA of the knee compared with placebo. Tanezumab was well tolerated, and reports of worsening OA and/or joint replacement were evenly distributed across the treatment groups.

This randomized, parallel-group, multicenter study evaluated long-term safety and efficacy of tanezumab in patients with chronic low back pain (CLBP). Patients from the parent study (NCT00876187) were eligible for this safety extension study within 12 weeks after last dose of parent study medication or upon discontinuation due to lack of efficacy. Patients received 3 intravenous then 4 subcutaneous administrations of tanezumab 10mg (n=321) or 20mg (n=527) at 8-week intervals. Safety assessments included adverse event documentation, physical and neurological examinations, and laboratory tests. Efficacy analyses included change from parent study Baseline in Brief Pain Inventory-short form, Roland-Morris Disability Questionnaire, and Patient’s Global Assessment of CLBP. The study discontinued prematurely due to an FDA-imposed clinical hold. Mean extension study treatment durationwas 194 and 202 days for tanezumab 10 and 20mg, respectively. The most frequently reported treatment-related adverse events were paresthesia, arthralgia, and hypoesthesia. Osteonecrosis was reported in 6 patients (tanezumab 10mg: n=2 [0.6%]; tanezumab 20mg: n=4 [0.8%]); 9 additional patients (tanezumab 10mg: n=7 [2.2%]; tanezumab 20mg: n=2 [0.4%]) underwent total joint replacement (TJR). Of these, all 6 patients with reported osteonecrosis and 4/9 undergoing TJR were evaluated by a blinded expert Adjudication Committee. Adjudication outcomes were: osteonecrosis (n=0); worsening osteoarthritis (OA; n=5); another diagnosis or indeterminate (n=5). Of the 5 patients adjudicated to worsening OA, 2 were adjudicated to normal progression, 1 was adjudicated to rapid progression of OA and in 2 patients the rate of OA progression was indeterminable. Improvements in efficacy observed in the parent study (at Week 16) weremaintained throughWeek 32 in this study. Both tanezumab doses significantly improved all efficacy outcomes from parent study Baseline to Week 32 in this extension study. In conclusion, long-term tanezumab was generally safe and provided durable efficacy in patients with CLBP. Supported by Pfizer, Inc.