Antibodies inhibiting nerve growth factor (NGF) are profoundly effective pain relievers in clinical trials, and, if approved, would become the first new class of analgesics for osteoarthritis, and possibly many other conditions, since the advent of non-steroidal anti-inflammatory drugs (NSAIDs). Now the US Food and Drug Administration (FDA) is reporting that NGF antibodies are associated with joint destruction. These adverse outcomes occurred more frequently when patients received higher doses of antibodies or took the agents along with NSAIDs, according to materials just posted on the FDA website in advance of the FDA’s Arthritis Advisory Committee meeting scheduled for March 12. At that time, the committee will review the data and recommend whether, and how, clinical testing of NGF antibodies can go forward.
Results reported in scientific papers and meeting abstracts over the last two years have indicated that NGF antibodies are phenomenal pain relievers, as heralded by the 2010 publication of a phase 2 study of a Pfizer antibody, tanezumab, for osteoarthritis knee pain (Lane et al., 2010). A number of companies sent multiple NGF antibodies into clinical trials for osteoarthritis, low back pain, and a host of other painful conditions, and Pfizer embarked on extensive phase 3 testing of their antibody for osteoarthritis. But in 2010 the FDA halted almost all of the trials, due to reports that patients were experiencing worrisome joint failures.
In the wake of the reported joint destruction, the only trials that have been allowed to proceed are phase 2 studies for bone pain from metastatic cancer. Now, the FDA advisory committee is charged with determining whether, on balance, the drugs warrant continued testing. If it does allow testing to resume, the committee is set to outline whether it will restrict patient eligibility for future trials, and will also specify the screening and safety monitoring protocols those trials must follow.
Do NGF antibodies have a future as revolutionary pain relievers, or will the FDA judge them too dangerous? Watch PRF for news from the upcoming meeting…
Image: X-ray of a knee with osteoarthritis. Credit: James Heilman, MD, Wikimedia Commons.