Tanezumab is a humanised monoclonal antibody that targets nerve growth factor (NGF), a neurotrophin that modulates pain processing and sensitivity via nociceptor sensitisation. It works by selectively targeting NGF and stopping it from activating receptors on pain-signalling neurons.
This Phase III study evaluated the efficacy of tanezumab in alleviating pain in patients with osteoarthritis (OA) of the hip, who had insufficient pain relief with, or were unable to take, non-opiate pain medications, and who had a Western Ontario and McMaster Universities OA Index (WOMAC) pain subscale score of ≥5 (with a ≥1 increase following washout of any pain medications) and physical function subscale score of ≥4 at baseline [all WOMAC scores were assessed using a numerical rating scale of 0-10]. Participants had to discontinue previous pain medications, and there was no active comparator used (so the efficacy of tanezumab compared to other commonly used analgesics was not determined).
Participants (n=621) were randomised to double-blind treatment with tanezumab (one of three doses) or placebo every 8 weeks (baseline, week 8 and week 16). The co-primary endpoints were change from baseline to week 16 in the WOMAC pain and physical function subscales and the patient’s global assessment (PGA). In the modified intention-to-treat population (n=611), treatment with all doses of tanezumab led to statistically significant improvements versus placebo for all the primary endpoints (p<0.001 for all). The absolute changes were as follows:
• WOMAC pain score: -1.62 with placebo, -2.90 with 2.5mg, -3.31 with 5mg and -3.37 with 10mg (largest absolute reduction versus placebo: 1.75 on a 10-point scale)
• WOMAC physical function: -1.39 with placebo, -2.57 with 2.5mg, -2.88 with 5mg and -3.00 with 10mg (largest absolute reduction versus placebo: 1.61 on a 10-point scale)
• PGA: -0.34 with placebo, -0.66 with 2,5mg, -0.78 with 5mg and -0.81 with 10mg (largest absolute reduction versus placebo: 0.47 on a 10-point scale)
Peripheral oedema, upper respiratory tract infections, pain in an extremity, arthralgia, paraesthesia, urinary tract infection and headache were reported in ≥5% of patients in at least one of the tanezumab dose groups. A total of 4.3% of the tanezumab-treated patients and 3.2% of the placebo-treated patients had findings suggestive of a new or worsened peripheral neuropathy at the time of their last neurological consultation.
Pfizer initiated a worldwide suspension of the tanezumab OA clinical trial program in 2010, after a small number of reports of patients treated with tanezumab experiencing worsening of OA leading to joint replacement. This was later lifted in 2012 as an FDA advisory committee voted to recommend continued drug development, but with a strong emphasis on close safety surveillance and careful patient selection. In the current study a total of 8 patients had joint replacements (5 in the tanezumab group); two of these had reported osteonecrosis.