SAN FRANCISCO, California—Tanezumab, a novel humanized monoclonal antibody that blocks nerve growth factor (NGF) signals, significantly reduced the pain of moderate to severe knee osteoarthritis (OA), according to phase II data reported by Nancy E. Lane, MD, at the American College of Rheumatology 2008 meeting.1

“Nerve growth factors are synthesized at sites of inflammation and appear to accentuate pain. Treatment with a monoclonal antibody against nerve growth factor, tanezumab, was very effective in reducing knee pain and improving physical function in patients with moderate to severe knee OA.”—Nancy E. Lane, MD
“Effective treatment to relieve pain in patients with osteoarthritis is an unmet medical need. Recent work has found that nerve growth factors are synthesized at sites of inflammation and appear to accentuate pain. Treatment with a monoclonal antibody against nerve growth factor, tanezumab, was very effective in reducing knee pain and improving physical function in patients with moderate to severe knee OA. Therefore, inhibition of nerve growth factor may provide a new type of therapy to reduce pain in OA and possibly other pain states,” said Dr. Lane, who is the director of the Aging Center at the University of California at Davis Medical Center.

Knee pain, patient global assessment both improved with tanezumab

The researchers enrolled 450 men and women aged 40 to 78 years who had previously failed NSAIDs or were candidates for procedures such as total joint replacement and had baseline knee pain with walking that was a ≥50 and ≤90 on a 0-100 mm Visual Analog Scale. Patients in the 16-week, randomized, placebo-controlled, parallel-arm, double-blind, multiple-dose study received 2 doses of either intravenous placebo or tanezumab at 10, 25, 50, 100, and 200 μg/kg on day 1 and day 56. The primary endpoints were knee pain with walking and patient global assessment of response to therapy.

Dr. Lane reported data for the 444 patients who were actually treated. These were 41% male, 88% white, with a mean age of 58.7 years and median time since OA diagnosis of 5.1 years.

“Tanezumab treatment improved knee pain and patient global assessment (P <.005, primary endpoints) compared with placebo over the 16 weeks. At weeks 12 and 16, significant improvement in WOMAC physical function, pain, and stiffness scores and more OMERACT-OARSI responders were noted in all tanezumab treatment groups versus placebo (Table),” Dr. Lane said.

Tanezumab 10 mcg/kg reduced walking pain in the affected knee from baseline to week 16 by a mean decrease of 32.1%, versus a decrease of 17.5% in the placebo group (P <.001). The 200 mcg/kg tanezumab doses reduced walking pain by 48.1% (P <.001 vs placebo) at week 16.

WOMAC Subscale Changes (LS mean±SE) and OMERACT-OARSI Responders (%) at Week 12 and Week 16
  Placebo 10 µg/kg 25 µg/kg 50 µg/kg 100 µg/kg 200 µg/kg
Physical function at baseline 69.0±1.5  63.8±1.6 69.2±1.7 62.6±1.5 67.4±1.7 67.8±1.7
Change from baseline to week 12 -15.0±3.1 -32.5±3.1* -34.7±3.0* -33.2±3.2* -43.7±3.0* -46.5±3.1*
Change from baseline to week 16 -15.9±3.1 -28.5±3.1† -29.9±3.0† -31.6±3.2* -41.1±3.0* -44.2±3.2*
Pain at baseline 69.0±1.4 65.8±1.6 69.2±1.4 62.1±1.4 68.3±1.5 68.4±1.4
Change from baseline to week 12 -16.5±3.2 -34.0±3.2* -36.7±3.1* -31.7±3.3* -44.0±3.1* -47.0±3.2*
Change from baseline to week 16 -17.5±3.3 -28.8±3.2† -31.9±3.1† -29.2±3.4† -40.7±3.2* -44.8±3.3*
Stiffness at baseline 74.4±1.6 69.7±1.5 75.0±1.4 66.7±2.1 71.2±2.1 73.3±1.6
Change from baseline to week 12 -17.8±3.3 -38.0±3.3* -38.9±3.2* -37.7±3.3* -45.6±3.2* -50.3±3.3*
Change from baseline to week 16 -17.8±3.4 -31.6±3.3† -33.9±3.2* -36.7±3.4* -42.9±3.2* -48.1±3.4*
OMERACT-OARSI Responders week 12 (%) 52.1 67.6‡ 74.7‡ 73.6† 90.5* 91.7*
OMERACT-OARSI Responders week 16 (%) 49.3 60.8 66.7 69.4‡ 86.5*  87.5*

*P <.001 vs placebo; †P <.01; ‡P ≤.03.

Treatment-related adverse effects were reported in 21% of tanezumab patients 8% of placebo patients. The most common adverse effects in the tanezumab groups were headache (8.9%), upper respiratory tract infection (7.3%), and paresthesia (6.8%).

“Administration of tanezumab once every 8 weeks resulted in a significant benefit for patients with painful knee OA, as assessed by OMERACT-OARSI responder index and WOMAC physical function, pain and stiffness scores,” Dr. Lane concluded. She said that phase III studies are underway.

This research was supported by Pfizer.

Reference

1. Lane NE, Schnitzer TJ, Smith MD, et al. Tanezumab relieves moderate to severe pain due to osteoarthritis (OA) of the knee: a phase 2 trial. Presented at the American College of Rheumatology 2008 meeting; San Francisco, Calif; October 28, 2008. Presentation 1989.