A panel of experts for the U.S. Food and Drugs Administration (FDA) this Monday recommended that the federal government should allow continued testing of an experimental class of pain drugs for arthritis, despite links to bone decay and joint failure.
The 21 member panel of arthritis experts voted unanimously that research on the nerve-blocking drugs should continue, with certain safety precautions. Reports of joint failure led the agency to halt studies of the drugs in 2010 before any of the medications could be submitted for U.S. approval.
The panel voted 21 to 0 in favor of a question that asked whether there was a role for continued development of the drugs. The panel then voted 20 to 1 in favor of a question that asked whether development of the drugs should be continued for pain conditions that currently don't have good treatments like chronic pancreatitis.
Pfizer Inc., Johnson & Johnson and Regeneron Pharmaceuticals have asked the FDA to lift the moratorium on testing of their drugs. The FDA will weigh the advice of its panel before making a final decision.
“There's clearly a worrisome safety signal, but in spite of that, I think there's an unmet need in certain patient populations,” said panelist Dr. Sherine Gabriel, of the Mayo Medical School in Rochester, Minn. Panelists noted that not all patients respond to medications currently on the market, like Aleve and aspirin. The experts also said that the drugs could prove useful in treating a variety of other chronic pain conditions for which there are few options. “Anything that has the hope of helping pain patients is worth pursuing,” said Susan Broyles, the patient representative on the panel.
These nerve growth factor inhibitors have been claimed as a potential breakthrough for treating osteoarthritis, back pain and other chronic pain conditions. Anti-inflammatory painkillers like Advil can cause stomach bleeding, while opiates carry a high risk of addiction The injectable nerve-silencing drugs offer a new approach, by blocking proteins that control pain sensations throughout the body.
Experts said more study is needed to determine why some patients taking the drugs saw their arthritis worsen, in some cases to the point of joint failure. Studies of these painkillers were halted in 2010 because of this troubling side effect, and at the time Dr. Nancy Lane, lead researcher on a trial looking at one of these drugs, tanezumab, said patients who ended up needing a knee replacement most likely harmed their damaged joint even further because they felt so good. “They probably accelerated the degeneration of the joint,” said Lane, director of the Aging Center, Medicine and Rheumatology, at the University of California, Davis. “Sometimes, pain is good in protecting you.”
Data analyses by the FDA showed a higher rate of joint problems among patients taking nerve-inhibitors and anti-inflammatory drugs at the same time. However, there were also cases of bone deterioration in patients taking the newer drugs alone.
Problems with nerve growth factor inhibitors first emerged in the summer of 2010, when the FDA asked Pfizer to halt studies of its experimental injection tanezumab in patients with osteoarthritis, low back pain and diabetic nerve pain. The action came after Pfizer researchers reported that osteoarthritis actually worsened in certain patients, requiring joint replacements in some cases.
In December that year the FDA put a research hold on all drugs in the class after similar problems emerged, halting studies by Johnson & Johnson and Regeneron Pharmaceuticals Inc. Regeneron was developing a compound called REGN475, in cooperation with Sanofi-Aventis. Johnson & Johnson was testing its drug fulranumab in several pain conditions.
The FDA lifted its hold on a trial of the drug for cancer pain last summer, though studies for osteoarthritis remain on hold.
“The risk of currently used available agents--NSAIDS and opioids is very high,” said Lenore Buckley, the chair of the panel and an internal medicine professor at Virginia Commonwealth University School of Medicine in Richmond. “Not many people want to say let's just give up on this class of medications at this point.”
Dr. Elaine Tozman, an associate professor in the division of rheumatology and immunology at the University of Miami Miller School of Medicine, said she doesn't think this new painkiller would add much to the treatment of osteoarthritis. “This is really a drug which is for a symptom of osteoarthritis, it's really for pain,” she said. “As rheumatologists, most of us are looking for a drug that works on the underlying disease.” Tozman noted that patients with severe osteoarthritis of the knee usually go on to have a joint replacement.
“Based on the assessments of risk and benefit, we conclude that further clinical investigation of tanezumab in osteoarthritis and other forms of chronic pain is warranted with the protection of additional risk management and surveillance measures,” Pfizer said in FDA briefing documents. “Chronic pain affects millions of adults in the United States. For many patients, treatment of chronic pain is inadequate in part due to the limitations in the availability of effective treatments and inadequate patient and clinician knowledge about the best ways to manage chronic pain.” For its part, Regeneron stated “... there may be a role for anti-NGF therapy in pain conditions where there is a high unmet need, i.e., those for which there are no adequate alternatives.”
Although the FDA is not required to follow the recommendations of its advisory panels, it usually does.
Some 27 million adults in the United States have osteoarthritis, with the knee being the most affected joint, according to the U.S. Centers for Disease Control and Prevention. The number of people with osteoarthritis of the knee is expected to rise as baby boomers age and as obesity among Americans increases, Lane noted.