PARIS — Tanezumab, a novel inhibitor of nerve growth factor, significantly eased knee pain in patients with moderately severe osteoarthritis, according to the findings of a large, phase II, double-blind randomized trial.
Within 3 days after a first dose of tanezumab, many participants in the 440-patient trial experienced a greater-than-50% improvement in walking knee pain, as assessed by the Visual Analog Scale (VAS), Dr. Nancy E. Lane reported at the annual European Congress of Rheumatology.
“At higher doses, they had a 70%–80% reduction in knee pain that was maintained over 8 weeks. We've never seen that before, short of a joint replacement,” she said in an interview. The trial was sponsored by Pfizer Inc., where Dr. Lane serves as a consultant.
Other possible applications for tanezumab include cancer pain, degenerative disk disease pain, and fibromyalgia, said Dr. Lane, professor of internal medicine and director of the center for healthy aging at the University of California, Davis.
Tanezumab is a humanized monoclonal antibody against nerve growth factor (NGF). NGF, which is upregulated in locally inflamed tissue and pain states, stimulates the growth of sensory nerve cells peripherally and increases the response to pain.
The subjects had moderately severe osteoarthritis knee pain, with average baseline walking knee pain VAS scores of slightly more than 70 mm on a 0- to 100-mm scale. All were unresponsive to nonopiate pain medications or were candidates for total joint replacement or other surgical interventions. After a washout period, they were randomized to intravenous placebo or tanezumab at 10, 25, 50, 100, or 200 mcg/kg. Two doses were administered 8 weeks apart.
Patients in the placebo arm averaged an 18-mm decrease in walking knee pain from baseline to week 16, as assessed by VAS. Those on 10–50 mcg/kg of tanezumab averaged 29- to 34-mm reductions. And those on 100 or 200 mcg/kg of the NGF inhibitor averaged 46- and 48-mm reductions, respectively, in VAS pain scores.
The most common adverse events related to tanezumab were transient episodes of hypoesthesia, which occurred in nearly 11% of patients at the two highest doses. These localized areas of numbness or reduced appreciation of pain are consistent with the inhibition of NGF, as NGF is a sensitizer to pain, Dr. Lane explained.
In the phase III trials to come, it's likely that weight-adjusted dosing will be replaced by three non-weight-dependent doses, perhaps 2.5 mg, 5 mg, and 10 mg. This dosing format allows for titration, which is attractive in treating chronic pain, the physician continued.
There is a pressing need for better pharmacologic therapies for osteoarthritis pain. Many patients can't tolerate, or don't obtain, adequate pain relief with NSAIDs. In addition, cardiovascular issues limit the usefulness of NSAIDs in many older patients. Narcotic analgesics are efficacious for the management of pain related to knee osteoarthritis and other chronic diseases, but these drugs entail problems with addiction and various toxicities. Inhibition of NGF may offer an effective alternative option.
“For patients with moderately severe osteoarthritis of the knee who [don't want] a joint replacement or who want to put it off, a treatment that lasts for 2 months gives them a 'pain holiday' to rest and restore their energy so they can better deal with their disease,” Dr. Lane said.