The study’s results come with a word of caution. Lane and her colleagues completed the trial in 2007. In the years since, Pfizer started a number of phase II and III trials, but has since been ordered by the FDA to suspend them: Ensuing osteoarthritis trials caused a small number of participants to experience so much tissue degeneration that they required joint replacement surgery, and not necessarily on the joint they were undergoing treatment for.
More studies need to be done to determine whether the joint damage occurred because tanezumab was somehow affecting bone or because it was just so effective that the subjects were more active than they should have been and didn’t feel pain to warn them of serious injury. Lane believes it’s the latter. “It works so well that people are going to need to be counseled. Just because they don’t feel pain doesn’t mean their disease is gone,” she says. “Pain is good; it keeps us from doing too much. And this medication is very good, so good that it allows people to do more than they should.”
Getting pain relievers approved by the FDA has always been difficult, since there are so many drugs with a proven safety record and relatively good efficacy already commercially available. In the post-Vioxx era (the drug was approved then taken off the market after it was shown to increase risk of stroke and heart attack), the FDA sets the bar even higher.
Even if it turns out that tanezumab is acting on bone and doesn’t make it through the approval process, Mantyh says, the research is no less important: It proves nerve growth factor has an important role in driving skeletal pain and is thus a good target for pain relief. “In the end, if the drug doesn’t get approved for whatever reason, they have provided clinical data to show that [nerve growth factor] is a major player in driving the pain of osteoarthritis.”
Kevin Koch, the chief scientific officer and president of Boulder, Colorado-based Array Biopharma, says Pfizer should be congratulated on moving this aggressively. “Being the first is always the hardest,” he says. Array is working on its own type of nerve-growth-factor inhibitor, an orally administered version that lasts only 12 hours, rather than eight weeks. So he’s particularly interested in the outcome of tanezumab trials and the FDA’s approval process. “This is a very exciting mechanism,” Koch says. “This is by far the most effective new pain therapy I’ve seen.”