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—those outside the brain and spinal cord—which makes it different from opioids. Vertex says its new drug is expected to avoid opioids’ potential to lead to addiction.
The company said it had completed two randomized studies, the first in 1,118 people who had tummy tucks and the other in 1,073 people who had shell surgery. The two procedures are commonly used in studies of people with acute pain, the temporary kind caused by something like surgery and likely to subside over time.
In its clinical trials, Vertex measured the drug’s effect with a standard pain scale in which patients rated the severity of pain from 1 to 10, with 10 being the most severe. Those taking his drug had a statistically and clinically significant reduction in pain, he says. A third study looked at the drug’s safety and tolerability in people experiencing pain from various conditions.
Excited by the results, which have yet to be published or presented at a meeting, Vertex plans to apply to the Food and Drug Administration by mid-year for approval to market the drug, a pill currently called VX -548.
The company has not said when full results and data will be available, but scientists not involved in the drug’s development said the information it released was promising.
Dr. Henry Kranzler, professor of psychiatry and director of the Center for Addiction Studies at the Perelman School of Medicine at the University of Pennsylvania, 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 effectiveness that, while not better than the opioid oxycodone, 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 received a $1,000 speaking fee from the company. He predicted that the Vertex drug would be only the first foray into this new territory.
“I like to think it’s the beginning of non-addictive pain medication,” he said.
That, said Dr. James P. Rathmell, professor of anesthesia at Harvard Medical School, “is the dream that all of us in this business have had for a long time.”
Currently, most people who need relief from moderate to severe pain have two options: drugs such as ibuprofen and COX-2 inhibitors or opioids. Medicines such as ibuprofen are not very effective, and opioids, as is known, can be addictive due to their mode of action. 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 most serious public health concerns in the United States, began more than two decades ago and involved people who started taking the drugs for pain but became addicted. As states tightened regulations on prescription opioids, many turned to illegal street drugs like heroin and fentanyl. Although doctors are more cautious about prescribing opioids now, many still do so because there are few alternatives.
Efforts to develop a new class of drugs to treat pain began in earnest in the 1990s. Researchers asked whether there were sodium channels that were specific to peripheral nerves. These are gates that open to send pain signals from nerves to the brain and then close to stop transmitting. If there were gates that only controlled signals from peripheral nerves, this suggested the potential for drugs to block them and control pain without affecting the brain and without causing addiction. Pain can be stopped at its source.
So the researchers began scouring the globe for people who had genetic mutations that prevented peripheral nerves from transmitting pain signals or that caused peripheral nerves to signal pain almost constantly. If they found these mutations, the genes involved could be targeted with drugs.
Eventually, they found both types of mutations.
In Alabama, a gene mutation has given one family a condition known as burning man syndrome that overextends peripheral nerves. People feel a terrible pain that some have said is like hot lava inside them. Any kind of warmth can bring it on – wearing socks or sweaters or going outside when it’s 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 felt no pain.”
These 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 drug based on one of these genes.
“Every major company worked on them,” said Dr. David Altshuler, chief scientific officer of Vertex Pharmaceuticals.
But finding a drug that worked proved a difficult task. Vertex, Dr. Altshuler said, spent 20 years on the project.
The result is VX-548. It inhibits Nav1.8, temporarily blocking the protein needed by 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 nerve damage or injury in the lumbar spine.
For now, the drug Vertex, if approved, will only be used in a fairly narrow range of conditions. The greatest need is for non-addictive drugs to control chronic pain, and while studies are ongoing, for now only those with acute pain will benefit.