Vertex's non-opioid pain reliever shows promise in people recovering from surgery

“There is a tremendous need for novel non-opioid analgesics without abuse liability,” and Vertex’s findings represent “an important advance,” said Dr. Clifford J. Woolf, director of the FM Kirby Neurobiology Center and Boston Children’s Hospital. It will be important for Vertex to determine whether the drug also works in patients with chronic pain, such as diabetic neuropathy and low back pain, “where the clinical need is greatest,” he added.

Vertex compared multiple doses of the drug to placebo pills in two clinical trials that began last summer. In a study of 274 people recovering from bunion surgery and a study of 303 people recovering from a tummy tuck, the highest dose of Vertex’s drug tested significantly reduced pain compared to a placebo. But the treatment wasn’t without its side effects. Nausea, headache, and dizziness were relatively common.

The results were announced in a press release. The company has not released any clinical or preclinical data on the drug.

Paul Arnstein, a clinical nurse specialist in pain relief at Mass General Hospital, said in an email that the lack of details about how Vertex measured pain reduction over time made the data difficult to interpret. Vertex also compared the effectiveness of its drug to a combination of opioid and acetaminophen and found that its experimental pill worked better. But Arnstein said the opioids used in the comparison were given at lower doses and less frequently than what’s often used in hospital settings.

But despite these uncertainties, Arnstein said he was “excited that this novel analgesic is being studied.” Given efforts to reduce the amount of opioids used, “this would be a welcome addition to the pain management toolbox,” he said.

Scientists have been trying to develop non-addictive painkillers for many years. A class of pain receptors called voltage-gated sodium channels are an attractive target for researchers. Scientists have found that people with a rare genetic mutation that causes them to lack one of these receptors called Nav1.7 cannot feel pain. Studies in animals show that blocking Nav1.7, or a closely related receptor called Nav1.8, can reverse pain without the addictive properties of opioids, explained Bruce Bean, a neurobiologist at Harvard Medical School.

dr David Altshuler, Vertex’s head of global research and chief scientific officer, said drugs that selectively block these receptors are “almost a holy grail of pain research.” Several companies have tested Nav1.7 blockers in a clinical setting with unexpectedly mediocre results. Vertex’s drug targets the related receptor Nav1.8, and the company is on track to become the first company to test a selective blocker of this pain receptor in an advanced Phase 3 trial later this year.

“This is good news,” Bean said of the Vertex results, “especially given the disappointing results so far from Nav1.7 inhibitors. I would take it as cautiously encouraging.”

dr Antje Barreveld, assistant professor of anesthesiology at Tufts University School of Medicine, said “the sodium channel is an excellent target” for a new treatment. Sodium channel blockers work well as local anesthetics, but their side effects have historically been too strong to use as pills, she added.

This isn’t the biotech’s first attempt to block Nav1.8. The company has tested three other drugs against it. Altschuler said these studies helped show that the pain receptor is a good target for multiple types of pain, including acute, neuropathic, and musculoskeletal pain. But these earlier drugs had several problems, including more frequent side effects, higher doses, and problems taking the drug with food.

The new drug, administered at a lower dose than its predecessors, seems to overcome these problems. “The bar is set high for a new pain reliever,” said Paul Negulescu, head of Vertex’s research labs in San Diego, where the drugs were discovered. “It could be used by millions of people, so it has to be easy to take.”

dr Stephen Waxman, a professor of neurology, neurobiology and pharmacology at Yale University who has studied sodium channels, called the study an “important step forward in providing statistically significant evidence of clinically meaningful pain relief after treatment with a Nav1.8 blocker.” deliver.” He hopes it will stimulate further work on sodium channel blockers for other forms of pain, including chronic pain.

Barreveld cautioned that Vertex’s data is based on patient-reported pain scores. She wants to know if the study participants took other medications after they stopped their treatment with the Vertex drug. “What interests us clinically is whether patients are able to tolerate other medications, such as opioids and NSAIDs, and how their pain was weeks or months later.”

“Opioids are not bad. They’re great for post-op pain, but the problem is if they’re taken longer than necessary,” she added. “The longer you take opioids after surgery, the more likely you are to get stuck on them. Anything we can do to eliminate the postoperative need for opioids is excellent and we need that.”

Ryan Cross can be reached at [email protected] Follow him on Twitter @RLCscienceboss.