Pfizer and Eli Lilly’s nerve growth factor (NGF) inhibitor tanezumab has inched closer to becoming the first alternative to opioid analgesics for severe pain after hitting the mark in a phase 3 trial.
Two subcutaneous doses of tanezumab—given eight weeks apart—met all the objectives in the trial in patients with osteoarthritis pain, significantly improving pain, physical function and patients’ assessment of their symptoms compared to placebo over the 16-week study.
It’s an important win for the drug, which was held back for years in development by concerns over NGF inhibitor safety, and particularly accelerated joint destruction that required replacement surgery in some cases. That resulted in the FDA applying a clinical hold on NGF drugs in 2012 that wasn’t relaxed until 2015.
Pfizer and Lilly say safety data from the phase 3 trial showed that rapidly progressive osteoarthritis was seen in “less than 1.5%” of tanezumab-treated patients and wasn’t observed in the placebo group, and there were no cases of bone destruction or osteonecrosis—another toxicity previously linked to NGF drugs.
The results keep the two partners on course for a filing in 2019 and represent an important milestone for the NGF field given that Regeneron halted some arms in its phase 3 program for NGF rival fasinumab in osteoarthritis in May after the independent data monitoring committee called the risk-benefit profile of the drug at higher doses unfavorable.
Meantime, another NGF inhibitor—Amgen’s fulranumab—seems to have been shelved after former partners Johnson & Johnson and Takeda both handed rights to the drug back in 2016, while AbbVie also gave up on its candidate earlier in the decade.
Pfizer and Lilly’s persistence with the project over many years may be about to pay off, assuming their big phase 3 program, including six studies across osteoarthritis, chronic low back pain and cancer pain, continues to deliver results. The high-risk gamble has a big prize in the offing, given the pressing need for nonopioid drugs for severe and chronic pain without the addictive properties and side effects of opioid painkillers. The U.S. is currently in the grip of an opioid addiction epidemic, with an estimated 11.5 million people misusing these drugs, according to Department of Health and Human Services (DHHS) data. It’s widely thought that an effective nonopioid drug for severe, chronic pain could quickly become a blockbuster and, prior to the FDA’s clinical hold, analysts had predicted that NGF inhibitors could become an $11 billion product category in their own right.
Pricing will of course be an issue given that current opioid analgesics are very cheap; however, it’s worth noting that opioids often don’t work very well in challenging indications like osteoarthritis. That’s one reason Pfizer and Lilly picked up fast-track status from the FDA for tanezumab last year for osteoarthritis and chronic low back pain.