- Pfizer and Eli Lilly's case for their experimental non-opioid pain drug tanezumab looks to be on more solid ground, supported by results from a late-stage study which gave a fuller picture of the drug's safety profile.
- Phase 3 data presented Wednesday showed tanezumab improved pain and physical function compared to placebo in patients with osteoarthritis pain of the knee or hip. Importantly, no cases of osteonecrosis — a key concern with drugs like tanezumab — were observed.
- The drugmakers aren't at the finish line yet, though. A key test for tanezumab will be results from a 3,000-patient long-term safety study, results from which are expected in early 2019.
Tanezumab is part of a class of drugs known as nerve growth factor (NGF) inhibitors that had initially showed promise before safety concerns halted clinical development in 2010 and 2011.
Unusual joint damage in osteoarthritis patients, in particular, spurred the Food and Drug Administration to place study holds on three NGF inhibitors, before later clearing studies to proceed. Pfizer and Lilly subsequently partnered and restarted trials of the drug in 2015.
Questions around safety have persisted and remain an overhang to the companies' development program. Since 2015, though, tanezumab has avoided any major red flags.
Pfizer and Lilly reported in July their Phase 3 study of tanezumab met all three of its co-primary endpoints, disclosing at the time a brief summary of the drug's safety profile.
On Wednesday, investors got a more detailed look at both safety and efficacy results from the trial. Rapidly progressive osteoarthritis (RPOA) was observed in 1.3% of tanezumab-treated patients, compared to no cases reported among the placebo group.
Less severe RPOA, characterized by joint space narrowing, was more frequent than joint damage or deterioration.
"Investors were particularly worried that the RPOA events would consist largely of Type 2, the more rapid and worrisome form of bone loss/destruction, than Type 1," wrote Credit Suisse analyst Vamil Divan in an Oct. 24 note to clients.
However, the companies reported an imbalance in total joint replacement surgery between the treatment and control arms. Three and a half percent of patients given 2.5 mg tanezumab received the surgery, while 6.9% on 2.5/5 mg tanezumab did. Only 1.7% of those treated with placebo went on to have the surgery.
Divan noted nearly all the surgeries were considered normal osteoarthritic progression, and took place after the treatment period.
A final verdict of tanezumab's safety profile, though, won't come until next year.
"We need all the data and the caution on tanezumab remains the safety study," Lilly CEO Dave Ricks said on a second quarter earnings call in July. "There is a large safety study that will read out in 2019 and that's really the pivotal question to answer on this program."
On the efficacy side of the ledger, tanezumab improved pain and physical function as measured by an 11-point score and patient assessment of their osteoarthritis. Data on all three measures across both doses of tanezumab met statistical significance.
Adjusted for placebo responses, though, the score reductions look a touch less impressive than was previously expected — a potential lift to rival Regeneron Pharmaceuticals, which is also advancing an NGF inhibitor called fasinumab.
Recently reported Phase 3 data for fasinumab in patients with osteoarthritis pain showed reductions in pain and function scores for the highest dose that appear slightly greater than tanezumab's after adjusting for placebo.
Response rates from placebo-treated patients were higher in the tanezumab study, however — one example of the challenges of comparing study results across trials.
Pfizer and Lilly are also developing tanezumab for chronic lower back pain and cancer pain, part of a bet that non-opioid treatments for pain will be needed as the overdose epidemic remains a top public health concern.