The Food and Drug Administration approved a new medication Thursday to treat pain from an injury or surgery. It is expensive, with a list price of $15.50 per pill. But unlike opioid pain medicines, it cannot become addictive.
That is because the drug, suzetrigine, made by Vertex Pharmaceuticals and to be sold as Journavx, works only on nerves outside the brain, blocking pain signals. It cannot get into the brain.
Researchers say they expect it to be the first of a new generation of more powerful nonaddictive drugs to relieve pain.
To test the drug, Vertex, which is based in Boston, conducted two large clinical trials, each with approximately 1,000 patients who had pain from surgery. They were randomly assigned to get a placebo; to get the opioid sold as Vicodin, a widely used combination pain medicine of acetaminophen (Tylenol) and hydrocodone; or to get suzetrigine.
In one trial, patients had an abdominoplasty, or tummy tuck. In the other, they had a bunionectomy. Side effects of suzetrigine reported by patients were similar to the ones reported by those taking the placebo.
The company also submitted data from a 250-person study that assessed the drug’s safety and tolerability in patients with pain from surgery, trauma or accidents.
Suzetrigine eased pain as much as the combination opioid. Both were better than the placebo at relieving pain.
Suzetrigine’s price, though, is much higher than that of acetaminophen plus hydrocodone. Patients are expected to take two pills a day, for a total cost of $31 a day. The older drug, said Dr. John D. Loeser, an emeritus pain expert at the University of Washington, is “dirt cheap” at pennies per pill.
But suzetrigine does not have opioids’ unpleasant side effects like nausea and drowsiness, and it is nonaddictive.
“There are a number of people who, once they have an opioid, want an opioid constantly,” Dr. Loeser said.
About 85,000 people a year become addicted after taking a prescription opioid, said Dr. David Altshuler, chief scientific officer at Vertex. It’s a small proportion of the 40 million prescribed opioids each year for acute pain — from surgery, accidents or trauma — but is nonetheless a large number, he said.
The story of suzetrigine began in the late 1990s with basic research by Dr. Stephen Waxman of Yale. He wondered how nerve cells signal pain to the brain.
Nerve cells have nine sodium channels — tiny molecular batteries — that generate electrical signals.
But, he discovered, two of those channels are only active outside the brain. One, called Nav1.7, is like the fuse for a firecracker, Dr. Waxman said. A nerve cell activates Nav1.7. That signal, in turn, activates a second channel, Nav1.8, which, he said, sends electrical signals of pain to the brain.
It seemed that a drug that could block Nav1.7 or Nav1.8 could be a potent pain medication that would have no effects on the brain, and therefore would not be addictive. (Dr. Waxman is not paid by Vertex, but does consult for other companies working on similar drugs.)
But there was another piece of the puzzle: Were these lab results applicable to humans?
If the lab work was predictive, people with mutations that made Nav1.7 or Nav1.8 fire constantly would be in constant pain. And people with the opposite mutation — one that blocked the channels — should feel no pain.
Both sorts of mutations would be extremely rare, if they existed.
Dr. Waxman contacted pain physicians across the entire Northern Hemisphere, asking if they had patients who had constant, intractable pain that could be caused by mutations that made Nav1.7 or Nav1.8 overactive. He came up empty-handed.
Then, in 2004, the Erythromelalgia Association told him about a family in Alabama whose members were wracked with pain. Most had ended up addicted to opioids and were unable to go to school or to work. Their condition was called “Man on Fire syndrome.”
Dr. Waxman and his colleagues found that the members of this family had a mutation in the Nav1.7 channel that made their pain nerves fire constantly.
Another group of researchers reported that a family in Pakistan whose members felt no pain had a mutation that blocked the same channel from firing. People called them firewalkers because they could walk on hot coals and feel nothing, which they did for money.
Vertex’s new drug, which blocks the Nav1.8 channel, is highly specific — the other sodium channels are left alone by the drug. Suzetrigine’s effects disappear when people stop taking the pills.
But although people with acute pain might need such a drug, there is also another group that needs pain relief but has few good options — those who have damaged nerves that cause constant pain, called peripheral neuropathic pain. That group includes people with diabetes, which can make the hands or feet hurt or go numb, among other symptoms. And it includes people with lumbosacral radiculopathy, or pinched nerves in the spine. Sciatica is one form of this condition.
In small studies, Vertex found that suzetrigine helped those with diabetic neuropathy, but was no better than placebo in those with pinched spinal nerves.
But, Dr. Altshuler said, the company is going ahead with larger studies in both groups of patients. While analysts and researchers deemed the results disappointing in patients with pinched nerves in their spines, the company decided to proceed because there are no approved drugs for the painful condition, and because the drug is safe and “the mechanism of action is so clearly validated.”
“No one has ever helped these four million people,” he said.
