Vertex Non-Opioid Pain Candidate Shows Promising Phase II Results

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Pictured: Man emptying a bottle of pills onto his hand/iStock, outline205

Vertex Pharmaceuticals on Wednesday unveiled positive Phase II data for its investigational, non-opioid voltage-gated sodium channel inhibitor VX-548, significantly easing pain in patients with diabetic peripheral neuropathy.

After 12 weeks, patients treated with the 23-mg, once-daily dose of VX-548 saw a mean reduction of 2.18 points on the 11-point Numeric Pain Rating Scale (NPRS), a standard and subjective tool that asks patients to rate the severity of their experienced pain. This effect was statistically significant with a p-value less than 0.0001, according to Vertex’s announcement.

Higher doses of VX-548 elicited similar effects. Patients given the 45-mg, once-daily schedule saw a mean NPRS decrease of 2.11 points, while scores in the 69-mg, once-daily arm dropped by an average of 2.26 points. Both effects were likewise statistically significant.

By comparison, the reference drug—Pfizer’s Lyrica (pregabalin)—elicited an average NPRS decrease of 2.09 at 12 weeks. Lyrica is indicated for neuropathic pain associated with diabetic peripheral neuropathy (DPN), as well as fibromyalgia, postherpetic neuralgia and pain related to spinal cord injuries.

Vertex was trading 7% higher in pre-market Wednesday in reaction to the readout.

In terms of safety, VX-548’s tolerability profile was good overall with most adverse events being mild or moderate in severity. The most common side effects included a decrease in creatinine clearance, peripheral edema, dizziness and weight gain.

One patient in the mid-level VX-548 dose group died, though the cause was determined to be atherosclerotic cardiovascular disease and was not related to the study drug.

Vertex CMO Carmen Bozic in a statement said that VX-548 demonstrated a “favorable benefit/risk profile in the Phase II study, which provides “further validation of the analgesic effects of NaV1.8 inhibitors.”

The Boston-based biotech is “working with urgency” to bring VX-548 into Phase III, “with the goal of changing the standard of care for neuropathic pain,” Bozic said. Vertex is also launching a second Phase II study of VX-548 in peripheral neuropathic pain—this time focusing on lumbosacral radiculopathy.

VX-548 is an orally available and selective inhibitor of the voltage-gated sodium channel inhibitor NaV1.8, which is central to pain signaling in the peripheral nervous system. VX-548 could represent a new class of painkillers that can provide strong pain relief without the typical drawbacks of opioids, particularly their addictive potential.

In an August 2023 interview with BioSpace, Vertex spokesperson Heather Nichols said that VX-548 could also be the first new class of pain medication in over two decades, and that it “could redefine the treatment of pain.”

Vertex is also developing VX-548 for acute pain, for which the biotech has three Phase III studies, with data expected in the first quarter of 2024.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at or

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