An experimental arthritis drug from Pfizer Inc. reduced pain more than researchers anticipated, doctors said. It also allowed previously hobbled patients to overuse and permanently damage their joints.
Bone destruction developed in 16 of 6,800 patients taking the medicine, tanezumab, as part of Pfizer’s (NYSE: PFE) development program, and they all needed a complete joint replacement for the affected knee, hip or shoulder, according to a report in the New England Journal of Medicine. Pain-free patients may have put excessive pressure on their fragile joints because they weren’t getting natural pain signals to take it easy, said the lead researcher, Nancy Lane.
“This is more potent than any pain medication I have ever had in arthritis,” said Lane, director of the Center for Aging at the University of California at Davis School of Medicine in Sacramento, in a telephone interview. “Because this is a new chapter in controlling pain, we didn’t realize we needed to counsel our patients in using their joints that were still diseased. Now we need to figure out how to use it so the risks don’t outweigh the benefits.”
New York-based Pfizer halted studies of the drug for osteoarthritis, chronic back pain and diabetes-related nerve disorders at the request of U.S. regulators in June and July. The market potential for tanezumab and similar medicines was estimated at $11 billion, Catherine Arnold, a New York-based managing director at Credit Suisse, wrote in a May 3 note to investors before the drug problems emerged.
Talking with FDA Pfizer is discussing tanezumab’s development program with officials at the U.S. Food and Drug Administration, said MacKay Jimeson, a company spokesman. The definitive cause of the complication hasn’t been determined.
Studies of the drug in patients with cancer pain and chronic pancreatitis are under way. Publication of the paper underscores the scientific interest in finding new methods to treat pain, Jimeson said.
Lane’s group studied 450 patients with moderate to severe osteoarthritis, a disease of the cartilage that protects the ends of bones in a joint. The tissue absorbs the impact from movement and allows the bones to slide along each other with less friction. For 27 million Americans with osteoarthritis, the cartilage wears away, causing pain and swelling and limiting motion.
Patients in the study received an injection of tanezumab or placebo on the first day and during the eighth week of treatment. Almost half of the patients were already candidates for joint replacement because of damage. Reduction in knee pain ranged from 45 percent to 62 percent in those given the Pfizer drug, depending on the dose, compared with 22 percent for those given placebo.
Side effects The most common side effects were headaches, colds and numbness or tingling of the skin.
The findings, from the second of three stages needed for regulatory approval, prompted Pfizer to move the medicine into final studies. It was in those 13 trials involving 9,100 patients that the rapid progression of arthritis occurred in 16 people, triggering regulators to put the research on hold.
“Pain has an important role in the avoidance of self-harm, but chronic inflammatory pain has generally been considered to be wholly undesirable,” said John Wood, professor of neurobiology at University College London, in an editorial that accompanied the research. “The study by Lane et al. suggests that a complete quenching of pain in patients with osteoarthritis may not necessarily be a good thing.”
Different joint For more than half of the 16 patients, worsening arthritis and the need for surgery occurred in a joint other than the one originally targeted in the study, the researchers said. One patient developed a problem in the shoulder, an uncommon location for damage from osteoarthritis.
Tanezumab, a nerve growth factor inhibitor, was considered one of Pfizer’s most promising compounds in development.
Similar treatments are in early stages of development at Johnson & Johnson (NYSE: JNJ) of New Brunswick, N.J.; Regeneron Pharmaceuticals Inc. (Nasdaq: REGN) of Tarrytown, N.Y.; Sanofi-Aventis SA (NSYE: SNY) of Paris; Abbott Laboratories (NYSE: ABT) of Abbott Park, Ill.; and AstraZeneca Plc (NYSE: AZN) of London, Lane said.
“I’ve never worked with anything that’s been this good for pain,” Lane said. “I’m not saying it’s perfect, but it is a game changer, provided we learn how to use it.”