Vertex scores double win with non-opioid pain drug

Vertex Pharma could be close to succeeding in the long-standing quest to find an alternative to potentially addictive opioids for the treatment of pain associated with common medical procedures.

Vertex's candidate, called VX-548, targets NaV1.8 sodium channels, which are thought to play a role in relaying pain signals to the spinal cord from peripheral nerves. It has been shown to be effective in treating moderate to severe acute pain in a pair of phase 3 trials involving common surgical procedures, and will now be filed for approval in the US later this year.

If approved, it could be a major step forwards in the bid to find effective pain relief free of the side effects and risk of dependency that accompanies the use of opioids and has fuelled an epidemic of overdose deaths in the US and other countries around the world.

The two trials – which compared VX-548 to placebo in patients undergoing abdominoplasty and bunionectomy surgery, respectively – were accompanied by a single-arm safety and effectiveness study of the drug in various surgical and non-surgical pain settings.

Treatment with the drug was associated with a statistically significant improvement on the primary endpoint of the time-weighted sum of the pain intensity difference in the first 48 hours after a procedure, with “clinically meaningful” improvements on that measure across both studies.

Pain relief typically kicked in within two to four hours, according to Vertex, and VX-540 was also associated with manageable side effects, mainly minor complaints like nausea, headache, and constipation, with no severe adverse reactions recorded.

The trials also compared VX-540 with an active comparator; namely, the opioid hydrocodone, given in combination with acetaminophen.

While it wasn’t found to be superior to that standard therapy for acute pain in both trials, Vertex’s drug offers the possibility to “fill the gap between medicines with good tolerability, but limited efficacy, and opioid medicines with therapeutic efficacy, but known risks,” said the company’s chief executive, Reshma Kewalramani.

“We are working with urgency to file the new drug application for VX-548 and bring this non-opioid medicine to the millions of patients who suffer from acute pain each year in the US,” he added.

Vertex already has breakthrough and fast-track designations from the FDA for the new drug, and analysts have previously suggested that, if it reaches the market with a broad label for acute pain, it could achieve sales of $5 billion or more a year at its peak.

In December, the company also reported data suggesting VX-548 may also be effective in neuropathic pain experienced by patients with diabetic peripheral neuropathy, which doesn’t tend to respond well to conventional analgesics.

Earlier efforts to develop non-opioid painkillers for acute pain applications have revolved mainly around nerve growth factor inhibitors, but the two leaders in the category, Eli Lilly and Regeneron, have both pulled the plug on their programmes in this area in the last few years.

Vertex has been developing inhibitors to the NaV1.8 sodium channel for many years and previously abandoned other candidates because they were not selective enough for the target and inhibited other channels, leading to side effects.

“The phase 3 safety and efficacy across the three studies are impressive and demonstrate VX-548’s potential to change the paradigm of pain management,” said Jessica Oswald, a specialist in emergency and pain medicine at the University of California San Diego, who sits on Vertex’s pain steering committee.

“I look forward to the potential of having a new class of acute pain medicine – the first in more than two decades – to use as an alternative to opioids to help the millions of people impacted by acute pain,” she added.