The Food and Drug Administration on Thursday approved a new type of nonopioid painkiller from Vertex Pharmaceuticals, NBC News reported.
The drug, Journavx, or suzetrigine, was approved to treat moderate to severe acute, or short-term, pain in adults. Experts say the drug, which is billed as nonaddictive, could reduce the number of opioids patients are prescribed after surgery or be used by patients who can’t take other pain medications — though several told NBC News they would like to see more research.
In a statement, Dr. Jacqueline Corrigan-Curay, the acting director for the FDA's Center for Drug Evaluation and Research, called the approval “an important public health milestone in acute pain management.”
“I think in acute pain this drug has great promise,” said Michael Schatman, a clinical instructor in the department of anesthesiology, perioperative care and pain medicine at NYU Grossman School of Medicine. “This is something that could be opioid-sparing, and we need more tools in our armory for pain.”
Although the number of patients going home from surgery with opioids has declined in recent years, many patients still leave the hospital with prescriptions. Despite the risks, opioids are extremely effective at treating pain, which has left doctors and patients with few options when acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs, such as ibuprofen, aren’t enough.
“We know from CDC data that anyone who gets exposed to opioids has the potential to have dependence on them,” said Dr. Richard Rosenquist, enterprise chairman in the department of pain management in the Neurological Institute at the Cleveland Clinic.
The body registers pain through nerve endings throughout the body. Touch a hot stove, for example, and the nerve will send signals to the spinal cord and up to the brain that you’re experiencing pain in your hand.
Opioids work by stimulating opioid receptors in the brain, blocking those pain signals. During the process, the brain also floods with the neurotransmitter dopamine, creating feelings of euphoria and activating the brain’s reward system. That’s why opioids can be incredibly addictive.
Vertex’s drug works in a completely different way, by blocking the pain signal from traveling to the brain in the first place. The signal is triggered by sodium molecules rushing into the nerve ending, sending the message onward to the brain.
Suzetrigine is a sodium channel blocker, the same type of drug as lidocaine. Lidocaine, a local anesthetic, works by blocking all sodium channels in the area it’s applied to — for example, the gums during dental work. A sodium channel blocker taken as a pill, such as suzetrigine, must be much more precise, as sodium channels are found throughout the body and are critical for heart and brain function. Suzetrigine blocks nerve pulses from just one sodium channel, called NaV1.8, from reaching the brain and being interpreted as pain.
“This is the first time we have had something that targets a specific sodium channel,” said Rosenquist, who wasn't involved with the research on the drug.
The process also doesn’t stimulate opioid receptors or produce any feelings of euphoria, he said.
“Right now all the evidence suggests this has no addiction potential at all,” Rosenquist said. “It’s no different than Tylenol or ibuprofen in terms of addiction potential.”
Tummy tucks and bunion surgery
In phase 3 clinical trials by the drugmaker, researchers looked at how well the drug worked after surgery. Patients who had undergone either tummy tucks or bunion surgery were given either suzetrigine every 12 hours; an opioid, hydrocodone, plus Tylenol every six hours; or a placebo for 48 hours after the operations.
Some of the patients who got suzetrigine also took ibuprofen as a so-called rescue medication — that is, if they were still experiencing pain after their suzetrigine doses.
“The results we have now do not tell us a lot about how much of a rescue medication was used,” said Dr. David Rind, chief medical officer at the Institute for Clinical and Economic Review (ICER), a nonprofit group that evaluates the cost, safety and efficacy of drugs. “We don’t know if they would have had higher pain reduction if they had just taken an NSAID from the start.”
Both tummy tuck and bunion surgery patients who got suzetrigine reported about a 50% reduction in their pain after 48 hours, similar to the reduction in pain reported by patients who got the opioid plus Tylenol.
About 50% of people in the tummy tuck group and about 30% in the bunion surgery group reported some kind of side effect, most commonly headache, constipation or nausea, but, except for constipation, the side effects were less common in patients who got suzetrigine compared with an opioid.
The dose of hydrocodone was also smaller than what is typically given after surgery, “so it’s hard to know exactly what to make of the results,” Rind said.
In another phase 3 study, patients taking suzetrigine for either surgery or acute pain rated how well they thought it worked. Participants took it every 12 hours for 14 days or until their pain subsided. In that study, 82% of surgical patients and 91% of nonsurgical patients said suzetrigine was good, very good or excellent at treating their pain. About 37% experienced some kind of adverse event, but most were mild, including headache, constipation, nausea, falling or having rashes.
Dr. Todd Bertoch, chief medical officer for pain research at CenExel JBR Clinical Research in Salt Lake City, led the phase 3 trials for suzetrigine in people who had undergone either tummy tucks or or bunion surgery.
While the clinical trial showed the drug could be effective as a solo treatment for pain — though it was more effective when patients combined it with ibuprofen — suzetrigine is meant to be used as part of a step-up approach, after Tylenol and NSAIDs, Bertoch said.
“If I still have pain after that, I’m kind of stuck. My next step is an opioid,” he said. “The goal is to make the next step not an opioid, and that’s what suzetrigine does.”
Suzetrigine could also be used in patients for whom Tylenol or NSAIDs aren’t safe, such as those with kidney or liver disease, he added.
Questions remain, but doctors see promise
In a report last month by ICER, a panel of experts rated the current data on suzetrigine as “promising but inconclusive.” By the group’s definition, that means it is moderately certain the drug would provide a small or substantial benefit to patients and a small — but not zero — chance of negative health consequences.
How much potential risk of harm is tolerable depends on the type of drug it is, Rind said. For example, it’s widely accepted that cancer drugs have harsh side effects but not enough to outweigh the potential benefit of treating an often fatal disease.
In those situations, “you are willing to accept a higher risk,” Rind said. “With a new pain reliever, it really has to be incredibly safe to be OK, and we really will not know that until it’s on the market and used by lots of people.”
New drugs like suzetrigine should be tried first in people who can’t take other pain medications, he said. For example, someone who has a history of both gastrointestinal bleeding, which makes taking NSAIDs dangerous, and addiction, which would deter a doctor from prescribing opioids, would be a good candidate for suzetrigine.
“There are a lot of people like that. It’s not like that is a tiny segment of the population,” Rind said.
Despite remaining questions about the drug’s efficacy and long-term safety, Rind said the physicians he has spoken with are excited about the drug.
“We have heard from pretty much every pain expert we talked to about how excited they are to have a new class of pain drugs in a space where there hasn’t been a new class of drugs in a very long time,” he said.
Schatman, of NYU Grossman School of Medicine, said suzetrigine does seem safe and effective for short-term use; however, he voiced concerns that Vertex doesn’t have longer-term safety data. (Schatman is the senior medical adviser for Apurano Pharma, a German biotech company, and he is working on a similar drug for chronic pain.)
“There is relatively strong safety data for short-term use, and that is what the FDA requires,” he said, but there is no set definition for how long acute pain lasts. Vertex isn’t pursuing the FDA’s approval for suzetrigine to treat chronic pain — a phase 2 clinical trial looking at suzetrigine for sciatica found that it performed no better than a placebo at reducing pain after 12 weeks — but it is common for doctors to prescribe acute pain medications off-label for chronic pain. That, he said, is worrying.
“My biggest concern is that we have drugs that are demonstrating as effective for acute pain that all of a sudden extrapolate the data to chronic pain,” he said.
Because suzetrigine blocks pain signals in the peripheral nervous system — the nerves that carry signals to the central nervous system — the drug most likely won’t work for chronic pain, which is usually based in the central nervous system, said Dr. Holly Geyer, a hospital internal medicine practitioner at the Mayo Clinic in Rochester, Minnesota.
Rosenquist said that even if further studies show suzetrigine doesn’t block acute pain better than opioids, he believes it is still likely to have a place in pain management.
“You have this tool that you can give to people in instances where they are discharged, they are in that recovery process, we are asking them to do rehab or walking or stuff like that, and would have gone home with an opioid,” he said. “The step-up approach is a reasonable way to approach this. It could play a role in reducing the overall exposure to opioids.”
Whether doctors reach for the drug will most likely depend on its cost, Schatman and Rosenquist said. Rind, of ICER, said it is likely to depend on both how Vertex prices the new drug and in what contexts, if any, private insurers cover it.
“The bottom line is NSAIDs, generic opioids and acetaminophen are cheap,” Schatman said, adding that he hopes suzetrigine is priced in a way that allows patients to access it.
This article first appeared on chof360.com. Read more from NBC News here:
