After VX-548 demonstrated significant pain relief in surgical and non-surgical settings, Vertex Pharmaceuticals is preparing to file a New Drug Application for the non-opioid candidate by mid-2024.
Pictured: Vertex Pharmaceuticals office in Boston, Massachusetts/iStock, hapabapa
Vertex Pharmaceuticals announced on Tuesday that its non-opioid pain treatment VX-548 aced three Phase III studies, inducing significant pain reductions in surgical and non-surgical settings.
Two of these late-stage studies assessed VX-548 in patients who had undergone either a tummy tuck—also known as abdominoplasty—or bunionectomy, which is a corrective procedure to remove a bone deformity in the toes. In both cases, the candidate was primarily evaluated according to the time-weighted sum of the pain intensity difference from 0 to 48 hours after surgery (SPID48).
Compared with placebo, VX-548 improved SPID48 scores among abdominoplasty patients, an effect that was highly statistically significant with a p-value less than 0.0001, according to Vertex’s announcement. The non-opioid pain reliever had a similarly strong effect in the bunionectomy trial, with a p-value of 0.0002, the company said.
Both abdominoplasty and bunionectomy patients also reported a “clinically meaningful reduction in pain” 48 hours after VX-548 treatment, as measured by the Numeric Pain Rating Scale (NPRS).
In addition, VX-548 demonstrated a more rapid onset of meaningful pain relief than placebo. Abdominoplasty patients reported that they felt the pain treatment take effect after a median of two hours, while the median onset in the bunionectomy study was four hours. By comparison, those taking a placebo experienced pain relief after a median of eight hours.
Vertex’s third Phase III study, a single-arm safety and effectiveness trial, also showed that VX-548 was effective at easing various surgical and non-surgical pain. Using the Patient Global Assessment tool, 83.2% of patients surveyed said that Vertex’s candidate was good, very good or excellent at treating their pain.
“The VX-548 benefit-risk profile ideally positions it to potentially fill the gap between medicines with good tolerability but limited efficacy and opioid medicines with therapeutic efficacy but known risks, including addictive potential,” Vertex CEO Reshma Kewalramani said in a statement.
With these data in hand, Vertex is “working with urgency” to submit a New Drug Application for VX-548, Kewalramani added. The company expects to file its application by mid-2024, seeking a broad label in moderate-to-severe acute pain.
Vertex is also aiming for a broad label for VX-548 in peripheral neuropathic pain, for which the company posted promising Phase II data in December 2023. In patients with diabetic peripheral neuropathy, 12 weeks of treatment with VX-548 led to a significant reduction in self-reported pain, as measured by the NPRS. Vertex is now preparing to move VX-548 into pivotal development for this indication.
Designed to be orally available, VX-548 is a selective blocker of the voltage-gated sodium channel inhibitor NaV1.8, which is a key player in peripheral pain signaling. In August 2023, Vertex spokesperson Heather Nichols told BioSpace that VX-548 could open up the first new class of pain treatments in over two decades.
“We believe we could redefine the treatment of pain with the first new mechanism of action in decades,” Nichols said at the time.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
