Phase 2 study finds that halted investigational compound reduces OA knee pain

Less than 3 months after halting studies regarding an investigational compound designed to reduce pain and improve function in patients with moderate-to-severe osteoarthritis of the knee, a phase 2 clinical trial has found that the drug leads to “only a few” minor side effects and a “substantial” improvement in patient conditions.

The 16-week study using the recombinant humanized monoclonal antibody which binds and targets nerve growth factors (tanezumab, Pfizer, Inc.) was published in a recent issue of The New England Journal of Medicine. Research — including several phase 3 studies — on the drug was halted by the manufacturer at the request of the FDA in July after other longer-term studies indicated that tanezumab may accelerate osteoarthritis (OA).

“The bottom line is this is a very effective drug for relieving pain,” Thomas J. Schnitzer, PhD, a lead author of the study, stated in a University of California, Davis press release. “Unfortunately, it appears some people go on to have their osteoarthritis progress more quickly. The long-term safety of tanezumab needs to be better understood.”

Side effects

In the new study, investigators randomized 450 patients who experienced knee pain from walking to receive one of various dosages of tanezumab or a placebo, given by injection at the start of the study and then again 8 weeks later. Participants were asked to regularly rate their pain and other aspects of physical functioning on a scale of one to 100.

The group found that during the 16 weeks of the study, walking knee pain was reduced from baseline by up to 62% in subjects given tanezumab vs. 22% in those given the placebo.

Tanezumab was also found to be superior to placebo in relieving stiffness and improving physical function.

Side effects were described as both temporary and minor, reported in 68% of patients in the tanezumab group and 55% in those given the placebo. A higher dose of tanezumab made a patient more likely to develop side effects, according to the release. These effects included headache, cold-like symptoms, paresthesias and diminished deep-tendon reflexes.

Potential indications

Long-term troubles found in previous studies could be the result of simple errors in judgment, the authors theorized.

“I believe that the apparent worsening of certain patients’ condition may be due to the fact that tanezumab works so well,” Nancy E. Lane, MD, a lead author of the study, stated in the release. “People feel so much better that they become more active, putting increased stress on their already badly diseased joints.”

Lane added that careful identification of appropriate candidates is crucial for the drug’s safe and appropriate use, noting that giving it to those patients with the most severe disease “is probably not a wise choice.”

According to the study authors, the FDA is currently examining the data to determine how to proceed.

Reference:
Lane NE, Schnitzer TJ, Birbara CA, et al. Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med. 2010; 363:1521-1531.
www.ucdmc.ucdavis.edu

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