Results, Safety

Pfizer and Lilly’s tanezumab largely makes the efficacy cut in second PhIII study, but safety issues continue to blight anti-NGF drug

Stark safety issues in the field of anti-NGF pain drugs have led a number of high profile drugmakers to press pause on development, reduce doses or abandon their efforts altogether. On Tuesday, Lilly and Pfizer’s offering — tanezumab — largely passed muster in terms of efficacy in patients with osteoarthritis (OA) pain in a late-stage study, but was unable to shake off that safety issue — triggering aggressive osteoarthritis in a small percentage of patients.

The Phase III 849-patient trial tested two doses of tanezumab (2.5 mg and 5 mg) against a placebo in moderate-to-severe patients that suffered symptoms despite treatment or intolerance to at least three different classes of analgesics, and on average had OA for more than six years. Patients given the higher dose met all three co-primary goals versus the placebo at 24 weeks: a statistically significant improvement in pain, physical function and overall OA assessment. Although those on the lower dose met the first two endpoints, the 2.5 mg dose failed to spur a statistical difference in overall OA assessment against the placebo.

Meanwhile, a number of safety issues emerged, akin to the results of a previous Phase III study reported last October that evaluated the use of the drug for 16 weeks. In the new trial, rapidly progressive osteoarthritis was observed in 2.1% of tanezumab-treated patients, while no such events were observed in the placebo arm.

There was also one event of osteonecrosis (a loss of blood to the bone that causes the bone to die) and one event of subchondral insufficiency fracture (a slowly healing fracture of the bone situated immediately below the cartilage of a joint) observed in patients treated with the drug, and once again no such events were reported in patients who got the placebo, the companies said, adding that detailed data would be presented at a future medical meeting.

Years ago, the promise of anti-nerve growth factor antibodies inspired analysts to project multibillion-dollar markets for the class of drugs. But a slew of safety issues forced the FDA to impose clinical holds on keenly watched drugs after reports of patients blowing their joints out — some have speculated that the drugs almost work too well, dulling pain and thus helping patients become more active, but also accelerating the pace of cartilage deterioration at the joints.

Nonetheless, such safety setbacks forced Pfizer $PFE to cut back on tanezumab doses, although it did not deter Lilly $LLY from pouring as much as $1.8 billion to buy into the drug. Teva $TEVA and Regeneron $REGN too were compelled to trim down their dose of anti-NGF drug fasinumab after similar concerns, while drugmakers such as J&J $JNJ , AstraZeneca $AZN and AbbVie $ABBV washed their hands of their anti-NGF offerings.

Tanezumab is being tested in a slate of Phase III trials, outside of the two whose results have been already reported. Pivotal data in patients with chronic lower back pain are expected later this year, and data from patients with cancer pain due to bone metastases are also incoming.

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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