Safety Concerns Force Regeneron to Halt High Doses of NGF-Inhibitor Fasinumab in Phase III Trial

Clinical Trial Halt

Regeneron has halted high dose treatment of a Phase III osteoarthritis drug following a risk-benefit assessment conducted by an Independent Data Monitoring Committee.

Regeneron will cut the doses of fasinumab, an antibody targeting Nerve Growth Factor (NGF). The drug is being tested in a late-stage trial for the treatment of osteoarthritis of the knee or hip and chronic low back pain in patients with concomitant osteoarthritis of the knee or hip. Little information was provided as to the concerns the committee noted. Regeneron announced the change in the fasinumab trial during its quarterly report, which was released this morning.

The committee recommended that the high dose-regimens be discontinued in the trial but recommended the study be continued using lower doses. Regeneron said the Phase III trial will be modified accordingly, despite the known safety risks. What dose levels the trial will continue with were also not disclosed this morning.

Last year Regeneron initiated two different Phase III studies with fasinumab. One study in chronic low back pain in patients with concomitant osteoarthritis was initiated in the fourth quarter of 2017. The other study, a Phase III efficacy study with multiple nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with pain due to osteoarthritis was also initiated in the fourth quarter of 2017.  

Fasinumab is a fully human monoclonal antibody that targets NGF, a protein that plays a central role in the regulation of pain signaling. There is evidence that NGF levels are elevated in patients with chronic pain conditions. It is estimated that 30 million people suffer pain from osteoarthritis, and the same number of people with chronic low back pain in the United States.

This is not the first time fasinumab has had some troubles due to safety risks. Two years ago the U.S. Food and Drug Administration placed a Phase IIb study on clinical hold after observing a case of adjudicated arthropathy, a disease of the joint. The patient, who had advanced osteoarthritis at study entry, had been receiving a high dose of fasinumab during the trial, Regeneron announced at the time.

The trial was placed on hold only months after Teva Pharmaceuticals handed over $250 million to secure a deal with Regeneron to advance the development of fasinumab.

One of the benefits of fasinumab, if it is approved, could be the reduction of dependence on opioid-based medications to combat acute pain. Opioid prescriptions account for 40 percent of the chronic pain market and carry a well-known risk of abuse and misuse, underscoring the need for alternative pain therapies without the medical and societal challenges.

Regeneron and Teva are not the only companies to jointly develop an anti-NGF. Eli Lilly and Pfizer are developing tanezumab for osteoarthritis pain. Last year the U.S. Food and Drug Administration granted tanezumab Fast Track designation, the first NGF inhibitor to receive the designation. Like Regeneron’s fasinumab, tanezumab has also had its share of problems. In 2010 Pfizer suspended development of the candidate due to the medication worsening osteoarthritis in patients and leading to joint replacements.

Subscription JPEG

Back to news