After halting studies on tanezumab, a drug that is extremely good at relieving pain and improving function in patients with moderate to severe osteoarthritis, a small phase II clinical trial has reported just a few slight side effects, and considerable improvement in the condition of patients. Details of the 16-week trial have been published in the New England Journal of Medicine. Previous longer-lasting trials have revealed that tanezumab may speed up the progression of osteoarthritis – the trial was subsequently suspended until the FDA (Food and Drug Administration) could check trial data and decide on its safety. Researchers believe this occurred because the drug worked too well – some patients may have overused their joints because the pain had gone, and damaged them more.
NSAIDs (non-steroidal anti-inflammatory inhibitors) are commonly used to treat osteoarthritis symptoms, however when used long term they can lead to serious problems, such as heart attacks, strokes, gastrointestinal bleeding, kidney dysfunction and ulcers. Examples of such medications include, aspirin, naproxen, ibuprofen and COX-2 inhibitors such as Celebrex and Vioxx.
Nancy E. Lane, professor of internal medicine and director of the UC Davis Center for Healthy Aging, principal investigator and co-author, said:
The need to find new drugs to treat osteoarthritis is critical. 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.
- Nerve growth factor is a small protein, it is vital for the maintenance, growth and survival of sympathetic and sensory neurons.
- In patients with osteoarthritis whose tissues are inflamed, growth factor levels tend to be much higher than normal.
- Tanezumab, a humanized monoclonal antibody, binds and inhibits nerve growth factor.
- Animal experiments showed that when growth factor is inhibited, the signs of pain are reduced.
- Consequently, scientists developed a new drug to block nerve growth factor.
Co-author, Thomas Schnitzer, a rheumatologist and professor of physical medicine and rehabilitation, said:
The bottom line is this is a very effective drug for relieving pain. 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.
In a Phase II trial, a new compound (drug) is tried out on hundreds of patients. The aim is to check for efficacy and safety – how well it works and how safe it is to use. Before entering the market, the compound will then be tried out in a Phase III study with some thousands of patients – the compound is compared to the best medication that is being used at that time for the targeted disease/condition.
Some Phase III trials were in progress when reports came in of a small number of patients developing accelerated osteoarthritis in the shoulders and hips. Pfizer, the creators of tanezumab were asked by the FDA to suspend the ongoing clinical trials in June 2010.
I believe that the apparent worsening of certain patients’ condition may be due to the fact that tanezumab works so well. People feel so much better that they become more active, putting increased stress on their already badly diseased joints.
Lane added that appropriate tanezumab candidates will have to be identified carefully, so that they can use the medication safely and appropriately.
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.
In this latest study, 450 osteoarthritis patients who had knee pain after/during walking were given varying dosages of either tanezumab or a placebo. They were given one injection on the first day and another after eight weeks.
They were asked to rate their pain and physical functioning on a scale of 1 to 100.
The researchers found that:
- Over 16 weeks, walking knee pain went down from baseline by up to 62% among the tanezumab patients
- Over 16 weeks, walking knee pain went down from baseline by up to 22% among the placebo patients
- The tanezumab patients experienced more relief from stiffness than the placebo patients
- The tanezumab patients experienced better physical function than the placebo patients
- Overall, the tanezunab patients found it easier to live with the degenerative joint disease
The effects of tanezumab were remarkable. 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.
55% of those on a placebo reported experiencing side effects, compared to 68% on the tanezumab. The researchers also report that those on higher tanezumab dosages were more likely to experience side effects. The most common side effects, which were temporary and deemed “minor”, were:
- Headache – 9%
- Cold-like symptoms – 7%
- Paresthesias – 7% (tingling, itchiness, numbness or hypersensitivity)
- Doctors found that some patients had diminished tendon reflexes when they tapped their knees or ankles with a medical hammer
Approximately 20 million people in the USA are affected with osteoarthritis, the authors inform. When the cartilage in the joints breaks down and eventually withers away, the patient experiences the hallmark symptoms of pain in the hips, spine, feet, hands and knees. At first, the sufferers usually only feel pain upon movement; in some severe cases, however, the pain is persistent, even while resting.
This is how drug development should be carried out. As with any potentially great new drug, you expect challenges, but the important thing is to carry out investigations in a responsible and open manner.
Source: UC Davis Health System
“Tanezumab for the Treatment of Pain from Osteoarthritis of the Knee”
Nancy E. Lane, M.D., Thomas J. Schnitzer, M.D., Ph.D., Charles A. Birbara, M.D., Masoud Mokhtarani, M.D., David L. Shelton, Ph.D., Mike D. Smith, Ph.D., and Mark T. Brown, M.D.
NEJM September 29, 2010 (10.1056/NEJMoa0901510)
Written by Christian Nordqvist