|
|
![]() |
![]() ![]() |
![]() |
|
||
![]() |
![]() |
The Hunt for a Nonaddictive Painkiller Bloomberg businessweek (Online) The Hunt for a Nonaddictive Painkiller By: Peebles, Angelica, Bloomberg Businessweek, 00077135, 11/7/2022, Issue 4761 A drug that doesn't cause cravings could shake up the $22 billion opioid market Edited by Rebecca Penty and David Rocks Prognosis When it comes to alleviating pain, nothing beats opioids, which have been used for thousands of years to replace discomfort with euphoria. Users can easily get hooked, however, particularly with lab-made versions such as fentanyl. In the US, opioids are responsible for three-quarters of overdose deaths. Drugmakers have little to show from years of searching for alternatives that don't pose the risk of addiction, but now an experimental candidate from Vertex Pharmaceuticals Inc. offers a glimmer of hope. The Boston drugmaker recently moved its painkiller, VX-548, into late-stage studies. The medicine blocks a sodium channel called Nav1.8, which plays an important role in telling the brain something's wrong. Sodium channels aren't anywhere near the brain, where addiction is triggered, making drugs that target them compelling potential substitutes for opioids. If Vertex can prove its drug is safe and effective, it could pave the way for a shake-up of a global opioid market estimated to be worth more than $22 billion annually. VX-548 would become a blockbuster even if it's approved only for use after surgery because the market for pain relief is so big, says Evercore ISI analyst Liisa Bayko. "If you just take a very small slice of that, you're talking about a tremendous amount of money," she says. Opioids include morphine; brand names such as OxyContin, Percocet and Vicodin; illegal heroin; and fentanyl, which can be found in both medical and illicit settings. The name "opioid" is derived from the opium poppy plant, which was consumed as early as 3400 B.C. The compound latches onto the body's opioid receptors, switching off parts of the brain that perceive pain and igniting a flood of the feel-good chemical dopamine, a tantalizing combination that often leaves people wanting more. About 3% to 5% of those who start opioids after a medical procedure continue taking them months later, meaning millions of people risk becoming addicted, says Michael Oshinsky, who oversees early pain research at the National Institutes of Health. The challenge with replacing opioids is to create a drug that's potent enough to relieve pain but selective enough to avoid unwanted effects. Companies such as Amgen, Pfizer and Roche have explored sodium channel blockers but have seen scant progress. Even Vertex, whose scientists started working on pain in 1996, has scrapped numerous prospects. The same group in the company is behind its successful cystic fibrosis drugs, the first of which was approved in 2012. Pain was supposed to be "the easy one," says Paul Negulescu, Vertex's senior vice president for research. "It worked out opposite to our expectations." Sodium channels inside the body act like gates that open to allow pain signals to travel from nerves to the brain. The idea is that if you close them, you can alleviate pain. Genetics reinforces this theory. Too little activity in the Nav1.7 channel, and a person can walk on hot coals without flinching. Too much activity, and a person feels as if they're on fire. Vertex believes the function of the Nav1.8 channel that it's targeting could be similar. Should late-stage trials confirm that the drug works, Vertex plans to seek approval for the treatment of acute pain or for temporary discomfort that's more intense than a headache and usually follows an injury or surgery, such as a knee replacement, a wisdom tooth removal or a broken arm. That segment of the market in the US is worth $4 billion, according to the company. Vertex is also testing the drug's effectiveness with broader types of pain, such as nerve damage stemming from diabetes. Eventually, it wants to see if VX-548 can treat chronic pain. Studies answering that question could take years, but the payoff could be enormous: One in 5 Americans suffers from chronic pain. Vertex says it's too early to talk about the potential price of its drug. Current treatments, many of which are generic, are low-cost; Wall Street analysts expect any novel pain drug to be more expensive. Vertex says that obstacle isn't insurmountable because so many people are desperate for a relief that doesn't put them at risk of addiction. VX-548 is likely more of a first step than a home run, says Stephen Waxman, director of the Center of Neuroscience and Regeneration Research at the Yale School of Medicine. Waxman identified the genetic mutation causing "man on fire" syndrome and has shown Nav1.7 and Nav1.8 operate in tandem to produce pain. "I view this as being like statins" that lower cholesterol, he says. "The first couple of statins that were developed were not terribly good by today's standards, but they were enough to energize the field." Although progress has been slow, Waxman says he's optimistic the new, much more effective nonaddictive pain medications are on their way. "It will not happen tomorrow or next month or even next year," he says. "The good news is there's a small army of very talented people working on it." THE BOTTOM LINE Opioids are effective, but they can be addictive. A potential alternative from Vertex targets the pain warning system far from the brain to prevent patients from getting hooked. |
![]() ![]() ![]() ![]() |
return to message board, top of board |