Tanezumab Works...in Smaller Trial

The results of a small, phase II clinical trial found only a few minor side effects and substantial improvement in patient conditions when treated with Pfizer Pharmaceutical’s experimental drug tanezumab.

The news comes just months after the company halted studies of the drug, which is used in reducing pain and improving function in people with moderate-to-severe osteoarthritis (OA) of the knee.

The results of the 16-week study are published in The New England Journal of Medicine.

Previous longer-term studies of the drug indicated that tanezumab may accelerate osteoarthritis. As a result, Pfizer chose to withdraw the drug from further study until the FDA reviews the data and determines whether it is safe.

Several Phase III trials were set for tanezumab before reports emerged that a small number of study subjects developed accelerated OA in the hips and shoulders.

“I believe that the apparent worsening of certain patients' condition may be due to the fact that tanezumab works so well,” said Nancy E. Lane, professor of internal medicine and director of the UC Davis Center for Healthy Aging, in a press release. “People feel so much better that they become more active, putting increased stress on their already badly diseased joints.”

“Giving tanezumab to people with the most severe disease is probably not a wise choice.

Increasing the activity level of a patient who already needs a joint replaced may not be in their best interest.”

Tanezumab is a humanized monoclaic antibody that binds and inhibits nerve growth factor (NGF). NGF is a small naturally occurring protein in the body and is important for the growth, maintenance, and survival of sympathetic and sensory neurons. NGF is found at high levels in inflamed tissues of patients with OA. Animal experiments have demonstrated that inhibiting the growth factor seems to reduce signs of pain. As a result, investigators developed the novel drug to block it.

Interest in these forms of treatment is growing due to the side effects of longterm use of common available medications such as NSAIDs. NSAIDs (aspirin, ibuprofen, naproxen, vioxx, etc.) may alleviate osteoarthritis symptoms but prolonged use can lead to gastrointestinal bleeding, ulcers, kidney dysfunction, heart attacks, and strokes.

“The need to find new drugs to treat osteoarthritis is critical,” Lane said. “We really don't have anything that slows its course, and most people with severe disease end up dependent on narcotic analgesics while waiting to have a joint replaced.”

Lane was a principal investigator and co-lead author of the new study along with Thomas J. Schnitzer of Northwestern Medicine in Chicago.

“The bottom line is this is a very effective drug for relieving pain,” said Schnitzer, a rheumatologist and professor of physical medicine and rehabilitation, in a 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.”

This study randomized 450 patients who experienced knee pain from walking. The patients received one of various dosages of tanezumab or a placebo, given by injection at the start of the study and again eight weeks later.

The participants regularly rated their pain and other aspects of physical functioning on a scale of 1 to 100. On average, over 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 taking placebo. Tanezumab treatment was also found to be superior to placebo in relieving stiffness, improving physical function, and helping patients live with degenerative joint disease.

“The effects of tanezumab were remarkable,” Lane said. “People on the drug went from having very limited activity to practically being on the dance floor. No medication available today has such dramatic results.”

Side effects of the drug were temporary and considered to be minor. Rates of side effects were 68% in the tanezumab group vs. 55% in subjects given placebo. Those given higher doses of tanezumab were more likely to develop side effects than those given lower doses.

Patients taking tanezumab most commonly developed headache (9%), cold-like symptoms (7%) and paresthesias (7%).Some patients given tanezumab also experienced diminished deep tendon reflexes, which are tested when a physician taps a patient's knee or ankle with a medical hammer.

OA is the most common joint disorder, affecting more than 20 million people in the country. It is caused by the breakdown and eventual loss of cartilage of the joints. OA causes pain of the hips, knees, hands, feet, and spine. The pain tends to worsen in humid weather and is often accompanied by joint swelling and stiffness. While initially pain occurs mainly with movement, the disease may become so advanced that a patient experiences severe pain even at rest.