A panel of independent arthritis experts recommended at a March 12, 2012, hearing that the U.S. Food and Drug Administration, or FDA, allow pharmaceutical companies to restart clinical trials of a new class of pain medications known as anti-nerve growth factor agents, or anti-NGFs.

Anti-NGFs are biologic drugs that block nerve growth factor, a protein associated with pain. Clinical trials showed them to have great promise in treating chronic pain from osteoarthritis, or OA, and other causes. But the trials were halted in 2010 after some patients experienced rapid progression of joint damage – specifically, bone death, also called osteonecrosis – requiring total joint replacements.

After reviewing data and receiving comments from drug makers, independent analysts and the public at the hearing, the 21-member panel voted unanimously to allow research to continue on anti-NGFs, provided safety measures are put in place. Ideas recommended by the panel include: testing anti-NGFs alone – not in combination with other medications, such as nonsteroidal anti-inflammatory drugs, or NSAIDs; monitoring patients’ bone health with X-rays and MRIs; and adequately warning trial participants of the potential risks.

The FDA is not obligated to follow the panel’s recommendations, but usually does. If eventually approved, anti-NGFs would be the first biologic drugs to treat OA pain and a variety of other pain conditions including chronic low back pain, diabetic peripheral neuropathy and cancer pain.

Until 2010, three companies had been conducting trials of anti-NGFs. Pfizer was furthest along, with phase 3 studies of its drug tanezumab. Two other companies were in phase 2 trials – Janssen Pharmaceuticals, a Johnson & Johnson company, with fulranumab, and Regeneron with REGN475. The drugs appeared to reduce pain much more effectively than NSAIDs or placebo.

For example, in a 2010 study of 450 knee OA patients, published in the New England Journal of Medicine, or NEJM, and sponsored by Pfizer, patients who received two intravenous administrations of tanezumab eight weeks apart reported 45 to 62 percent less pain, depending on the tanezumab dose – compared with a 22 percent pain reduction among those on placebo.

“The idea [is] that anti-NGFs can block the sensation of pain arising from the joint itself. NSAIDs are anti-inflammatories and may be less effective in people with causes of pain other than inflammation. There are many reasons for joint pain in OA that may not all be inflammatory in nature,” explains Amanda Nelson, MD, a practicing rheumatologist and researcher in OA and epidemiology at the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill. She has not conducted any research on anti-NGFs, but has helped analyze data from patients with OA as background material for Janssen Pharmaceuticals.

Despite data showing anti-NGFs’ promise for treating pain, in late 2010 and early 2011, the FDA asked the three drug makers to halt research out of safety concerns. Almost 500 joint replacement surgeries were performed among all study participants – raising questions about whether the anti-NGFs were accelerating joint degeneration. The drug makers complied, although trials of anti-NGFs for terminal cancer pain were allowed to continue because the benefits were believed to outweigh the risks for that group.