Vertex Pharmaceuticals of Boston announced Tuesday that it has developed an experimental drug that relieves moderate to severe pain by blocking pain signals before they reach the brain. It only works on peripheral nerves – outside the brain and spinal cord – which makes it the opposite of an opioid. Vertex says its new drug hopes to avoid the potential for opioid addiction.
The company said it completed two randomized studies, the first on 1,118 people who had abdominoplasty and the second on 1,073 people who had bunion surgery. Both procedures are commonly used in studies of people with acute pain, a temporary type of pain that is similar to a surgical procedure and is likely to subside over time.
In its clinical trials, Vertex measured the drug’s effects with a standard pain scale in which patients rated the severity of pain from 1 to 10, with 10 being the most severe. According to the report, those taking the drug experienced a statistically and clinically meaningful reduction in pain. A third study looked at the safety and tolerability of the drug in people experiencing pain from a variety of conditions.
Encouraged by the results, which have not yet been published or presented at the meeting, Vertex plans to apply to the Food and Drug Administration by mid-year for approval to market the drug, a pill, known for now as VX- It is called 548.
“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 an honorarium by the company. He predicted that the Vertex drug would be only the first foray into this new field.
“I think this is the beginning of non-addictive medications for pain,” he said.
Right now, most people needing relief from moderate to severe pain have two options: medications like ibuprofen and COX-2 inhibitors, or opioids. Medications like ibuprofen are not very effective, and opioids, as is well known, can be addictive because of the way they work. There’s 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 most serious public health concerns in the United States, began more than two decades ago and involves people who started taking medications for pain but became addicted. As states tightened regulation of prescription opioids, many people turned to illicit street drugs like heroin and fentanyl. Although doctors are now more cautious about prescribing opioids, many still do because there are fewer options.
Efforts to develop a new class of drugs to treat pain began in earnest in the 1990s. The researchers asked whether there were sodium channels that were specific to peripheral nerves. These are portals that open to send pain signals from nerves to the brain and then close to stop transmission. If there were portals that only controlled signals from peripheral nerves, this would suggest the possibility of drugs to block them and control pain without affecting the brain, and without causing addiction. Pain can be stopped at its source.
So researchers began searching for people around the world who had genetic mutations that prevented peripheral nerves from transmitting pain signals, or that caused peripheral nerves to signal pain almost constantly. If they find those mutations, the genes involved could be targeted with drugs.
Ultimately, they found both types of mutations.
In Alabama, a gene mutation caused a condition called Burning Man syndrome in a family, which causes peripheral nerves to become overactive. People feel a stinging pain, which some say is like hot lava inside them. Any kind of heat can bring it on – wearing socks or a sweater or going outside when it’s 70 degrees Fahrenheit.
“This is a tragic disease,” Dr. Waxman said. “It literally drives some people to suicide.”
After years of searching, researchers found people with gene mutations that caused adverse effects. This search started with a teenage boy from Pakistan. They earned money by walking on coals or cutting themselves with sharp blades in street demonstrations. His family members also had the same mutation, Dr. Waxman said, which included “painless fractures, painless burns, painless tooth extractions and painless childbirth.”
It’s not that people with such mutations feel less pain, he said; “He didn’t feel any pain.”
Those mutations and subsequent research led researchers to discover that two genes, known as Nav1.7 and 1.8, are needed to transmit pain. The race was on to find a medicine based on one of those genes.
“Every major company worked on them,” said Dr. David Altshuler, chief scientific officer of Vertex Pharmaceuticals.
But finding a drug that would work proved to be a difficult task. Vertex, Dr. Altschuler said, spent 20 years on the project.
The result is VX-548. It inhibits Nav1.8, temporarily blocking the gene so it can’t make the protein needed for nerves to transmit pain signals.
The study included people suffering from acute pain. But the company is now studying people with chronic pain from diabetic peripheral neuropathy and patients suffering from a type of back pain, lumbosacral radiculopathy, which is caused by nerve damage or injury to the lumbar spine.
For now, if the Vertex drug is approved, it will be used only in fairly limited situations. There is a greater need for non-addictive medications to control chronic pain, and while studies are ongoing, at the moment only those with acute pain will benefit.