Regeneron and Teva’s nerve growth factor (NGF) inhibitor fasinumab hit the mark in a phase III osteoarthritis trial, potentially setting up a race to the finish line in the non-opioid pain relief sector.
Top-line data from the trial in patients with OA of the knee or hip showed that at 16 weeks, fasinumab was associated with less pain and improved functional ability compared to placebo, hitting all its primary and secondary objectives. The results come a few weeks after rivals Eli Lilly and Pfizer reported positive phase III data for their NGF drug tanezumab in OA.
NGF inhibitors have had a chequered history, with a long list of discontinued candidates, mainly due to side effect issues, from the likes of AstraZeneca/Medimmune and AbbVie, amongst others. Amgen was also developing an NGF inhibitor called fulranumab – formerly partnered with Johnson & Johnson and Takeda – but the collaborators handed back rights in 2016 and the drug no longer features in Amgen’s pipeline report.
Fasinumab has had its own problems, with the FDA placing it under a clinical hold in 2016 after a case of joint destruction (arthropathy) was seen in its phase IIb trial. Earlier this year, Regeneron also revealed it had halted a high-dose arm in its study after a risk-benefit assessment suggested some patients might be at risk of what George Yancopoulos, Regeneron’s chief scientific officer, had described as “rapidly-progressing osteoarthritis.”
The FDA placed the entire class under clinical hold in 2010 after reports of severe arthropathy with some candidates in clinical trials, including come cases that required joint replacement.
Regeneron and Teva’s statement on the latest trial results suggests that fasinumab was well-tolerated, with a rate of arthropathy of around 2% higher than placebo – although the absolute rates have not been revealed.
Regeneron and Teva are still cautious about the prospects for fasinumab, limiting themselves to saying that the positive trial had set up additional phase III evaluations, rather than talking about a possible filing schedule.
“We are encouraged by these data and look forward to advancing our pivotal phase III fasinumab programme in patients with osteoarthritis of the knee or hip, who currently have very limited therapeutic choices to treat their chronic pain, other than with non-steroidal anti-inflammatory drugs or opioids,” said Yancopolous.
“This is a high-risk, high-reward program as we’ve described in the past,” he told analysts earlier this year. “It’s pretty well-demonstrated that the molecule has activity, but it also has certain side effects.”
Nevertheless, fasinumab and tanezumab are now leading what analysts consider could be a highly-lucrative market for drugs that deliver effective pain relief without the risk of side effects and addiction linked to opioid analgesics. In contrast to opioids, which alter pain perception by targeting opioid receptors, NGF inhibitors block signalling of a pathway activated in response to injury, inflammation, or chronic pain.