The FDA placed a clinical hold on a phase IIb trial of Teva and Regeneron's nerve growth factor (NGF) inhibitor fasinumab in chronic lower back pain on safety concerns.
The decision by the US regulator followed the discovery that one patient in the trial - who was on a high dose of fasinumab - developed arthropathy, the rapid destruction of a joint. It's a blow to the project and particularly Teva, which only last month licensed the drug in a deal valued at up to $2.6bn.
While the patient had advanced osteoarthritis on entry into the study and so was at elevated risk of arthropathy, the FDA called a halt to the trial as a precautionary measure. Arthropathy has been seen before with NGF inhibitors - and caused the agency to put the entire class under a clinical hold in 2011.
That regulatory restriction was only relaxed to a partial hold last year, allowing some NGF inhibitor candidates to restart clinical testing and raising hopes that the class could emerge as the first real alternative to opioid drugs for chronic pain.
Teva and Regeneron have now decided to design a new phase III trial in lower back pain that will exclude patients with advanced osteoarthritis, in the hope of getting regulatory approval to restart trials of fasinumab.
On the plus side, Teva and Regeneron took a look at the data accrued so far in the study and concluded that fasinumab improved pain scores at all doses compared to placebo, after both eight and 12 weeks of treatment. However, the updated results revealed what might be a dose-dependent increase in the risk of arthropathy with the drug.
Once tipped as a possible $11bn market, the NGF inhibitor development pathway is littered with discontinued projects such as AstraZeneca's Medi-578 and AbbVie's ABT-110, and analysts typically view the candidates still in trials as wild cards, potentially offering big rewards but also a having a high risk of failure.
Earlier this year, prospects for one of the most advanced candidates - Amgen's fulranumab - took a dive after licensees Johnson & Johnson and Takeda both decided to hand back rights, although they insisted that was because of changing priorities rather than safety concerns.
Eli Lilly and partner Pfizer also remain in the race with their tanezumab anti-NGF candidate, which restarted testing for osteoarthritis, chronic lower back pain, and cancer pain last year after the clinical hold was relaxed.
Regeneron's chief scientific officer George Yancopoulos said the new phase III trial will "maximise potential benefit for patients in need, while minimizing the likelihood of side effects."
"We look forward to working with global health authorities to advance this important investigational therapy for patients with often difficult-to-treat osteoarthritis pain and chronic low back pain," he added.