Vertex Pharmaceuticals has scored an FDA approval for Journavx (suzetrigine), a non-opioid pain reliever that could usher in a new era of nonaddictive therapy in the indication.
As an oral voltage-gated sodium channel (NaV) inhibitor, the first-in-class treatment targets a signaling pathway in the peripheral nervous system, preventing pain sensations from reaching the brain. It is the first significant innovation in treating pain in more than two decades.
Journavx has been cleared for adults with moderate to acute pain, which is usually short-term and often resulting from surgery or an injury. Opioids and other analgesics are often prescribed to treat the pain, but their use can lead to addiction.
The approval is “an important public health milestone,” Jacqueline Corrigan-Curay, M.D., acting director of the FDA’s Center for Drug Evaluation and Research, said in a release Thursday.
“A new non-opioid analgesic therapeutic class for acute pain offers an opportunity to mitigate certain risks associated with using an opioid for pain and provides patients with another treatment option,” Corrigan-Curay added.
Of the more than 80 million people in the U.S. who are prescribed drugs for moderate to severe acute pain each year, about half receive opioids, with roughly 85,000 developing opioid use disorder, Vertex said.
By blocking pain signals on the periphery nervous system and not in the brain, Journaux has not shown the potential to become addictive. In clinical trials, Journavx’s side effects have mostly been mild, including itching, rash, muscle spasms and an increased blood level of creatine phosphokinase.
“I believe Journavx could redefine the management of pain and become a foundational treatment option for people with all types of moderate-to-severe acute pain,” Jessica Oswald, M.D., associate physician in emergency medicine and pain medicine in San Diego and an adviser for Vertex, said in a release.
Vertex is angling Journavx to also be approved for chronic pain, which would open it up to a much larger patient population, though performance in the clinic in that indication has been mixed.
In December, the company reported results from a phase 2 trial in lumbosacral radiculopathy, which sent shares tumbling, despite the study meeting its primary endpoint.
While safety is the key differentiator between Journavx and the opioids with which it will compete, another differentiator is price as Vertex will charge $15.50 for a 50-mg dose of Journavx, which works out to $420 for a two-week course. William Blair analyst Myles Minter, Ph.D., noted that the price is half that of ICER's estimate for cost effectiveness, but far exceeds the approximate $0.50 price for generic opioids.
"Despite our view that suzetrigine will face initial inertia from clinicians for use in pain management, we model Journavx as attaining blockbuster status, reaching $1 billion in sales by 2028 and peaking at about $4.9 billion in sales in 2031," Minter added.
The approval culminates a long, painstaking development process, with Vertex emerging successful after several other companies abandoned their efforts to create a treatment using a similar mechanism of action.
The race in the industry to discover a medicine began more than two decades ago when two genetic mutations discovered in Asia gave scientists a better idea of how pain sensations traveled through the body. The mutations pointed to the NaV1.7 channel as the key transmitter of pain signals.
If pain-signaling ions are blocked from passing through the Nav1.7 channel, they can never reach the brain. But the target was elusive. Because NaV channels have so much similarity, targeting a particular one isn’t easy.
As Vertex examined data from studies run by other companies—and speculated on the types of compounds that were being investigated—its researchers believed that the process of “selective inhibition wasn’t being tested,” according to Vertex’s Paul Negulescu, Ph.D., who heads up the company’s research wing and guides its pain program.
“We tried to make those molecules ourselves and test them ourselves and just benchmark them against our compound,” Negulescu said in an interview with Fierce. “It was partially a belief in our hypothesis, but it was also an assessment that our failures weren’t disproving our hypothesis, so we kept going at it. In fact, I think (the failures were) further proving our hypothesis.”
While other companies were using patch-clamp electrophysiology—a method of measuring ion channel currents in cell membranes which was developed in the mid-1970s—Vertex employed a more advanced tool. Its electrical stimulation voltage ion probe reader allowed it to test many more potential compounds and with greater efficiency.
Another way that Vertex veered from the competition was to begin testing on the Nav1.8 channel, the function of which is closely related to the Nav1.7. In three clinical trials, the first of which started a decade ago, Vertex’s Nav1.8 inhibitors failed to succeed. Two years ago, the company finally struck gold with Journavx and moved it into later-stage trials.
In two phase 3 studies, Journavx topped placebo by a significant margin in relieving pain in the 48 hours after patients underwent tummy tuck and bunion removal procedures. The trials, however, failed to achieve their secondary endpoints, as Journavx was no more effective than widely used opioid painkiller Vicodin.