Boston-based Vertex Pharmaceuticals announced Tuesday that it has developed an experimental drug that relieves moderate to severe pain by blocking pain signals before they can reach the brain. It works only on peripheral nerves – those outside the brain and spinal cord – making it different from opioids. Vertex says its new drug should avoid opioids’ potential to lead to addiction.
The company reported that it has completed two randomized trials, the first in 1,118 people who had tummy tucks 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 caused 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 the severity of pain from 1 to 10, with 10 being the most severe. Those who took the drug had a statistically and clinically significant reduction in pain. A third study looked at the drug’s safety and tolerability in people suffering from pain due to several conditions.
Encouraged by the results, which have yet to be published or presented in a meeting, Vertex plans to ask the Food and Drug Administration by mid-year for marketing approval of the drug, a pill that, for now, is called VX- 548.
The company has not said when full results and data will be made available, but scientists who were not involved in the drug’s development said the information released by the company is promising.
Dr. Henry Kranzler, professor of psychiatry and director of the Center for Addiction Studies at the University of Pennsylvania’s Perelman School of Medicine, called the drug “a therapeutic breakthrough.”
He said its development is based on a strong body of science and, at least for acute pain, “looks very promising” with efficacy that, while no better than the opioid oxycodone, is no worse either.
“This has the potential to become a success story,” said Dr. Stephen Waxman, professor of neurology, neuroscience and pharmacology at Yale. Dr. Waxman was not associated with the study, but the company received a $1,000 honorarium for his lectures. He predicted that the Vertex drug would be just the first foray into this new industry.
“I like to think it’s the beginning of non-addictive pain medications,” he said.
This, said Dr. James P. Rathmell, a professor of anesthesiology at Harvard Medical School, “is the dream that all of us who work in this field have had for a long time.”
For now, most people who need moderate to severe pain relief have two options: medications such as ibuprofen and COX-2 inhibitors or opioids. Drugs such as ibuprofen are not very effective and opioids, as is known, can be addictive due to 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 most serious public health problems in the United States, began more than two decades ago and involved people who started taking pain medications but became addicted to them. As states tightened regulation of prescription opioids, many turned to illegal drugs like heroin and fentanyl. Although doctors are more cautious about prescribing opioids today, many still do so because there are few alternatives.
Efforts to develop a new class of pain medications began in earnest in the 1990s. The researchers asked whether there were sodium channels specific to peripheral nerves. These are portals that open to send pain signals from nerves to the brain and then close to stop the transmission. If there were portals that only controlled signals from peripheral nerves, this would suggest that drugs could block them and control pain without affecting the brain or causing addiction. The pain could be stopped at the source.
So researchers began scouring the world 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 those mutations, the genes involved could be targeted with drugs.
Ultimately, they found both types of mutations.
In Alabama, a genetic mutation has caused a family to develop a condition known as burning man syndrome that puts peripheral nerves into overload. People feel excruciating pain that some say is like hot lava inside them. Any type of heat can cause it: wearing socks or a sweater 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 research, researchers found people with a genetic mutation that led to the opposite effect. The discovery began with a teenager 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 births,” Dr. Waxman said.
It’s not that people with such mutations felt less pain, he said; “They didn’t feel any pain.”
Those mutations and subsequent research led researchers to discover that two genes are required 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 major company has worked on them,” said Dr. David Altshuler, chief scientific officer of Vertex Pharmaceuticals.
But it proved 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 nerves to transmit pain signals.
The studies involved people with acute pain. But the company is now studying people with chronic pain due to diabetic peripheral neuropathy and patients with a type of back pain, lumbosacral radiculopathy, caused by compromise 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 greatest need is for non-addictive medications to control chronic pain, and while studies are ongoing, for now only those with acute pain would benefit.