Vertex Pharmaceuticals of Boston announced Tuesday that it had developed an experimental drug that relieves moderate to severe pain, blocking pain signals before they can get to the brain. It works only on peripheral nerves — those outside the brain and the spinal cord — making it unlike opioids. Vertex says its new drug is expected to avoid opioids’ potential to lead to addiction.
The company reported that it had completed two randomized studies, the first in 1,118 people who had abdominoplasties and the other in 1,073 people who had bunion surgery. The two procedures are commonly used in studies of people with acute pain, the temporary kind that is brought on by something like a surgical procedure and is likely to ease with time.
In its clinical trials, Vertex measured the drug’s effect with a standard pain scale in which patients rated pain severity from 1 to 10, with 10 the most severe. Those taking its drug had a statistically and clinically meaningful reduction in pain, it reports. A third study looked at safety and tolerability of the drug in people experiencing pain from a variety of conditions.
Buoyed by the results, which are yet to be published or presented at a meeting, Vertex plans to apply to the Food and Drug Administration by midyear for approval to market the drug, a pill that, for now, is called VX-548.
The company has not said when the full results and data will be made available, but scientists who were not involved in the drug’s development said the information the company released was promising.
Dr. Henry Kranzler, professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania’s Perelman School of Medicine, called the drug “a therapeutic breakthrough.”
He said its development was based on a strong body of science and, at least for acute pain, “it looks very promising” with an efficacy that, while not better than the opioid oxycodone, also is not worse.
“This has the potential to be a blockbuster,” said Dr. Stephen Waxman, a professor of neurology, neuroscience and pharmacology at Yale. Dr. Waxman was not associated with the study but was paid a $1,000 speaking honorarium by the company. He predicted that the Vertex drug would be only the first foray into this new area.
“I like to think it’s the beginning of nonaddictive medicines for pain,” he said.
That, said Dr. James P. Rathmell, professor of anesthesia at Harvard Medical School, “is the dream all of us in this business have had for a long time.”
For now, most people needing relief from moderate to severe pain have two options: drugs like ibuprofen and COX-2 inhibitors, or opioids. The drugs like ibuprofen are not very effective, and the opioids, as is well known, can be addictive because of the way they work. There is no way to separate the effects of opioids — pain relief — from the side effects: changes in thinking, cognition, energy and emotions.
The opioid crisis, one of the gravest public health concerns in the United States, began more than two decades ago and included people who started out taking the drugs for pain but became addicted. As states tightened regulation of prescription opioids, many turned to illegal street drugs like heroin and fentanyl. Though doctors are more cautious about prescribing opioids now, many still do so because there are few alternatives.
Efforts to develop a new class of pain-treating drugs began in earnest in the 1990s. Researchers asked if there were sodium channels that were specific for peripheral nerves. These are portals that open to send pain signals from the nerves to the brain and then close to stop transmitting. If there were portals that only controlled signals from peripheral nerves, that suggested the possibility of drugs to block them and control pain without affecting the brain, and without causing addiction. Pain might be stopped at its source.
So researchers began scouring the globe for people who had genetic mutations that prevent peripheral nerves from transmitting pain signals, or that made peripheral nerves signal pain nearly constantly. If they found those mutations, the genes involved could be targeted with drugs.
Eventually, they found both types of mutations.
In Alabama, one gene mutation caused a family to have a condition known as burning man syndrome that puts peripheral nerves into overdrive. People feel a searing pain that some have said is like hot lava inside them. Any sort of warmth can bring it on — wearing socks or a sweater or going outside when it is 70 degrees Fahrenheit.
“It’s a tragic disease,” Dr. Waxman said. “It literally drives some to suicide.”
After years of searching, researchers found people with a gene mutation that led to the opposite effect. The discovery began with a teenage boy in Pakistan. He made money by walking on coals or cutting himself with sharp blades in street performances. His family members had the same mutation, with “painless fractures, painless burns, painless tooth extractions and painless childbirth,” Dr. Waxman said.
It’s not that people with such mutations felt less pain, he said; “they did not feel any pain.”
Those mutations and subsequent research led researchers to discover that two genes are needed to transmit pain, known as Nav1.7 and 1.8. The race was on to find a drug based on one of those genes.
“Every big company worked on them,” said Dr. David Altshuler, chief scientific officer of Vertex Pharmaceuticals.
But it turned out to be a difficult task to find a drug that worked. Vertex, Dr. Altshuler said, spent 20 years on the project.
The result is VX-548. It inhibits Nav1.8, temporarily blocking the protein needed for the nerves to transmit pain signals.
The studies involved people with acute pain. But the company is now studying people with chronic pain from diabetic peripheral neuropathy and patients with a type of back pain, lumbosacral radiculopathy, caused by impairment or injury to a nerve in the lumbar spine.
For now, the Vertex drug, if approved, would only be used on a fairly narrow range of conditions. The greater need is for nonaddictive drugs to control chronic pain, and while studies are underway, for now only those with acute pain would benefit.