Results from multiple Phase III trials show consistent improvements in pain relief and physical function.
When the FDA accepted tanezumab, a nerve growth factor inhibitor developed jointly by Pfizer and Eli Lilly, for a Biologics License Application (BLA) review in March, the monoclonal antibody was heralded as a potential first-in-class treatment for patients with moderate to severe osteoarthritis who experienced inadequate relief from other analgesics.
Now, approximately eight months later, results from multiple Phase III trials show consistent improvements in pain relief and physical function.
Osteoarthritis, also called degenerative joint disease, is the most common form of arthritis. It affects 32.5 million Americans, according to the Centers for Disease Control & Prevention. It causes pain or stiffness in the joints, swelling and reduced flexibility. There is no cure, so physicians focus on wellness and pain control. Tanezumab, which workers on the periphery, may offer an alternative to currently approved pain relief options.
In a poster presented at the virtual 145th Annual Meeting American Neurological Association (ANA) – one week before World Arthritis Day, October 12, 2020 – researchers from the Mayo Clinic, St. Elizabeth’s Medical Center, the University of Sydney, Pfizer and Eli Lilly & Company assessed improvements in co-primary endpoints. They used the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function and Patient’s Global Assessment of Osteoarthritis (PGA-OA), and conducted three double-blind Phase III studies to compare tanezumab to comparators.
In two of the studies, researchers enrolled osteoarthritis patients with a history of pain in the knee or hip who did not get sufficient relief from acetaminophen, oral nonsteroidal anti-inflammatory drugs (NSAIDs) and either tramadol or opioids. A third study included patients who were taking NSAIDs. In studies one and two, patients were injected with either tanezumab or placebo every eight weeks. In study three, their twice-daily dosage of NSAIDs was continued.
A total of 4,541 patients enrolled in those three studies. Some had a mid-study evaluation at week 16, but all were evaluated at week 24 when the trials concluded.
The researchers reported that all three co-primary endpoints for tanezumab were met for study one, at 2.5 mg doses. Study two, with 5 mg doses, “significantly improved all co-primary endpoints at week 24,” but met only two of the primary endpoints. Results of the Patient’s Global Assessment of Osteoarthritis (PGA) were not significantly affected. In study three, 5 mg doses “produced significant improvement in WOMAC Pain and Physical Function (but not PGA-OA) at week 16 compared to NSAID,” the researchers wrote in the abstract. Adverse events were comparable across the three studies.
The researchers concluded that 5 mg doses of tanezumab were more effective than NSAIDs at relieving pain and increasing function.
In a second poster presented at the ANA meeting, a different group from Pfizer, Eli Lilly and three American medical centers evaluated the long-term neurological safety of subcutaneous tanezumab treatment versus oral nonsteroidal anti-inflammatory drugs (NSAIDs) during a 56-week study.
Based on results from the 2,996 patients who participated in this study, researchers reported, “Increasing doses of tanezumab were associated with a higher incidence of adverse events in the form of abnormal peripheral sensation (APS).” Specifically, the rates of adverse events were 6.2% for patients receiving 2.5 mg doses of tanezumab and 9% for those receiving 5 mg doses. For the group receiving NSAIDs twice daily (and not tanezumab), however, the incidence was only 4.5%.
The most common adverse events for patients receiving tanezumab were hypoesthesia, paresthesia, and carpal tunnel syndrome. Less than 1% experienced worsening symptoms. Outside neurological examination revealed mononeuropathy rose from 1.3% in those receiving 2.5 mg doses to 2.1% in those receiving 5 mg doses. Radiculopathy, in contrast, was highest (0.9%) with the lower dose, and only 0.4% in the 5 mg dose group. None of the participants were diagnosed with sympathetic neuropathy.
“Adverse events of possible decreased sympathetic function were balanced across treatment groups, and there was no evidence of sympathetic nervous system dysfunction from tanezumab,” the researchers concluded.
Current treatment options provide insufficient relief for many osteoarthritis patients, causing them to try therapy after therapy.
“There is an urgent need for innovation in the treatment of osteoarthritis, as there have been no new classes of medicines available for this debilitating condition in more than a decade,” Ken Verburg, tanezumab development team leader, Pfizer Global Product Development, said last spring when announcing the BLA acceptance.
Tanezumab acts by interrupting the pain signal, preventing it from reaching the spinal cord or brain. Because levels of nerve growth factors increase after injury, inflammation or chronic pain, when tanezumab binds to NGF, it inhibits its action. This mechanism operates at the periphery, creating a marked contrast to the mechanisms of action of opioids, NSAIDs and other analgesics.
To data, research shows no risk of addiction, dependence or misuse. Tanezumab also is in Phase III trials to relieve cancer pain.
