Pfizer/Lilly NGF pain drug wins again, but safety concern won’t go away

osteoarthritis
Rates of joint damage are higher than in earlier phase 3 trial (Bruce Blaus CC BY-SA 4.0)

The long road to developing new painkillers targeting nerve growth factor (NGF) may be nearing an end, as Pfizer and Eli Lilly report efficacy for the second time with tanezumab in osteoarthritis.

Top-line data from the trial showed that tanezumab was able to cut pain significantly at the higher of two doses tested (2.5 mg and 5 mg) in subjects with moderate to severe OA compared to placebo. The results of Pfizer and Lilly’s earlier phase 3 trial reported last year showed efficacy at both dose levels.

The big question for Pfizer and Lilly is whether cases of joint damage seen in some patients will prove to be a concern for the FDA and other regulators if the program gets to the filing stage.

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In the latest study, rapidly progressive osteoarthritis (RPOA) was seen in 2.1% of patients on tanezumab versus none in the placebo group, and there was one case apiece of osteonecrosis and joint fracture—side effects that prompted the FDA to place all NGF inhibitors on a clinical hold in 2010.

That is an increase on the first phase 3 trial of tanezumab in OA, where the RPOA rate with the drug was 1.3% and there were no cases of osteonecrosis. Pfizer and Lilly made no comment on this in their prepared remarks on the trial, other than to say the data would be “submitted to a future medical congress.”

For now, there’s no word on radiographic data that could add color to the differences between the groups. After the first study results came out, Pfizer indicated that radiography suggested the majority of RPOA patients had “mild-to-moderate radiological change with mainly narrowing of the joint space,” with only a minority showing structural changes.

Safety aside, the efficacy readout keeps the duo in contention in the face to bring an NGF inhibitor to market as an alternative to opioids for chronic pain that avoid the risks of addiction. Their main rival—Regeneron and Teva’s fasinumab—is also in phase 3 development and cleared an osteoarthritis trial last year.

In the latest trial, 5 mg of tanezumab given as a subcutaneous injection every eight weeks met all three co-primary endpoints at 24 weeks, with statistically significant improvements in pain, physical function and the patients’ overall assessment of their symptoms compared to those taking placebo. The 2.5 mg dose achieved hit two of the three endpoints—pain and physical function.

All the patients in the trial had struggled to control pain and other symptoms using at least three other classes of painkiller and were reporting significant impact of the disease on their quality of life.

Pfizer and Lilly are now awaiting the results of additional trials in chronic lower back pain and pain associated cancer before moving ahead with regulatory filings.

Things are looking positive from an efficacy perspective, but all eyes will be on the safety data and a much clearer picture of this will come as additional phase 3 trials read out in the coming months.

Tanezumab and fasinumab are the last drugs standing among several NGF inhibitors developed over the years, with candidates from AstraZeneca/Medimmune, AbbVie and Amgen failing to make the cut. Analysts have suggested that drugs that offer opioid-like efficacy without the risk of side effects and addition could become a multibillion-dollar category.

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