Opioids, Setbacks

Nav1.7 analgesic failures stack up as Biogen abandons vixotrigine after latest setback

A slate of drug developers have reported failures in trials testing Nav1.7 inhibitors for pain management, calling into question the promise of the class of analgesics. On a conference call on Tuesday, Biogen disclosed that it was abandoning vixotrigine for sciatica pain after the experimental drug flopped in a study, adding to a string of failures already divulged by other drugmakers, including Roche, Teva and Xenon.

Available analgesics – NSAIDs, amine reuptake inhibitors, antiepileptic drugs and opioids — offer varying levels of analgesic efficacy, and are generally coupled with deleterious effects. In particular opioids — by far the most effective painkillers — are also one of the most abused class of drugs in the United States, with addiction levels and associated deaths hitting epidemic proportions. With researchers desperately seeking other avenues to treat pain, the protein Nav1.7 emerged as a viable candidate.

Nav1.7 controls the passage of sodium ions into sensory neurons, and the target garnered attention after it was found that rare human mutations characterized by a loss of function in Nav1.7 channels resulted in congenital insensitivity to pain. But the early wave of pharmaceutical interest in Nav1.7 drug development hit a wall, in part because it has been difficult to design molecules that can block just Nav1.7 and not closely related ion channels that play critical roles outside pain sensing. This trend seems to have continued this year.

Vixotrigine was acquired by Biogen $BIIB back in 2015 through its $675 million buyout of UK-based Covergence Pharmaceuticals. However, all is not lost as the drug continues to be evaluated as a treatment for trigeminal neuralgia and fiber neuropathy.

On Tuesday, Biogen also announced its drug, dapirolizumab pegol, which is being developed in collaboration with UCB (Euronext Brussels: $UCB), had failed to meet the primary endpoint in a Phase II study for lupus.

Meanwhile, Roche’s $RHBBY Genentech unit torched its Nav 1.7 inhibitor RG6029 which was being developed under a 7-year-old, $646 million deal with Canada’s Xenon $XENE last week. Xenon’s partner Teva $TEVA also bowed out of its 2012 collaboration to develop a similar inhibitor, TV-45070, this March.

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