New phase 3 data mean Pfizer and Eli Lilly have inched closer to getting their nerve growth factor (NGF) blocker tanezumab to the filing stage as an alternative to opioids for chronic pain.
The partners reported top-line results from the trial in the summer but have now unveiled the specifics to rheumatologists at the ACR/ACHP meeting in Chicago. They say the antibody met three of three primary objectives in patients with osteoarthritis of the knee and hip who struggle to control pain with opioids or nonsteroidal anti-inflammatory drugs (NSAIDs).
Five other late-stage studies are due to report in the first half of 2019 in OA, chronic lower back pain, and cancer pain and—if positive—could be followed quickly by regulatory filings. Pfizer and Lilly need to move fast if they are to keep tanezumab in contention with Regeneron and Teva’s rival NGF blocker fasinumab, which reported phase 3 data in OA in August.
The new study compared two doses of tanezumab to placebo and revealed that the NGF inhibitor was associated with a statistically significant improvement in pain, physical function and patients’ global assessment of their OA symptoms after 16 weeks.
One group of patients received a 2.5mg dose of the antibody as a subcutaneous injection at enrollment and after eight weeks, while a second got 2.5mg at baseline followed by 5mg. All told, 57.1% of patients on the drug given a higher dose of tanezumab experienced a 50% or greater reduction in pain at week 16, compared to 54.4% for the lower dose group and 37.9% for placebo.
Similar patterns were seen for physician function and patient-reported outcomes and, according to Ken Verburg, tanezumab development team leader at Pfizer, all three endpoints are “particularly meaningful, given that patients had moderate-to-severe pain and were unable to achieve adequate pain relief with other treatment options, including opioids and NSAIDs.”
There was one potential wobble, however, as treatment with the drug was associated with a higher level of joint replacement surgeries than placebo, resurrecting a longstanding concern about the safety of this drug class. The new data is hard to interpret, as there were no radiographic differences between the three groups.
All NGF inhibitors in clinical trials were placed on hold by the FDA in 2010 after being linked to a serious side effect called osteonecrosis, characterized by rapid destruction of joints, which set back development programs by several years, and subsequently led to both tanezumab and fasinumab having higher dose levels dropped from development.
Pfizer and Lilly say that joint replacement imbalance isn’t consistent with earlier tanezumab studies, and that the rate of rapidly progressive OA—importantly not classed as osteonecrosis—was low at 1.3% for the drug versus zero for placebo. A much clearer picture of the safety will come as additional phase 3 trials read out in the coming months.
Tanezumab and fasinumab are the survivors among a clutch of NGF-targeting drugs abandoned over the years, with the casualty list featuring candidates from AstraZeneca/Medimmune, AbbVie and Amgen.
If successful, they could tap into a multibillion-dollar market for painkillers that deliver potent pain relief without the risk of side effects and addiction linked to opioid drugs, particularly in the context of the current opioid addiction epidemic, with an estimated 11.5 million people in the U.S. misusing these drugs.