Positive results From the VX 548 phase III program for the treatment of moderate-to-severe acute pain

The Phase III program included two randomized, double-blind, placebo-controlled, pivotal trials, one following abdominoplasty surgery and one following bunionectomy surgery, as well as a single arm safety and effectiveness study which enrolled patients with a broad range of surgical and non-surgical pain conditions.

Treatment with VX 548 following abdominoplasty or bunionectomy surgery resulted in a statistically significant improvement on the primary endpoint of the time-weighted sum of the pain intensity difference from 0 to 48 hours (SPID48) compared to placebo as well as a clinically meaningful reduction in pain from baseline at 48 hours on the Numeric Pain Rating Scale (NPRS) in both studies (abdominoplasty: LS mean difference in SPID48 between VX 548 and placebo = 48.4 (95% CI: 33.6, 63.1; P<0.0001); bunionectomy: ls mean difference in spid48 between vx 548 and placebo="29.3" (95% ci: 14.0, 44.6; p="0.0002))."

For the first key secondary endpoint, Vertex tested the hypothesis that VX 548 was superior to hydrocodone bitartrate/acetaminophen (HB/APAP) on SPID48 following abdominoplasty surgery or bunionectomy surgery. Neither trial met this key secondary endpoint (abdominoplasty: LS mean difference between VX 548 and HB/APAP = 6.6 (95% CI: -5.4, 18.7; P=0.2781); bunionectomy: LS mean difference between VX 548 and HB/APAP = -20.2 (95% CI: -32.7, -7.7; P=0.0016)).

The second key secondary endpoint in both trials was time to meaningful pain relief defined as greater than 2-point reduction in NPRS from baseline compared to placebo. VX 548 had a more rapid onset to meaningful pain relief than placebo in both the abdominoplasty and bunionectomy trials. (The median time to meaningful pain relief was 8 hours for placebo in both studies compared to 2 hours in abdominoplasty and 4 hours in bunionectomy for VX 548, with nominal P<0.0001 and 0.0016, respectively.)

Other secondary endpoints in both trials were generally consistent with the primary endpoint.

The Phase III single arm safety and effectiveness study evaluated treatment with VX 548 for up to 14 days across a broad range of other surgical and non-surgical acute pain conditions and demonstrated favorable safety and tolerability, as well as effectiveness as measured by a Patient Global Assessment (PGA) at the end of treatment (83.2% of patients rated VX 548 as good, very good, or excellent in treating pain).

VX 548 was safe and well tolerated in all three Phase III studies. The majority of adverse events (AEs) were mild to moderate, and there were no serious adverse events (SAEs) related to VX 548. In general, AEs in the two randomized controlled trials were consistent with the post-surgical setting. In the VX 548 arm, the incidence of AEs was lower than placebo (patients with any AEs in VX-548 and placebo arms: 50.0% and 56.3%, respectively, following abdominoplasty, and 31.0% and 35.2%, respectively, following bunionectomy).

“We are very pleased with the results from the VX 548 pivotal program, which demonstrate a compelling and consistent combination of efficacy and safety across multiple acute pain conditions and settings. 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,” said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. “With FDA Breakthrough and Fast Track Designations in hand, 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 U.S.”

“As a physician treating patients suffering from pain for many years, I know firsthand the critical need for new, efficacious and safe treatment options,” said Jessica Oswald, M.D., M.P.H., Associate Physician in Emergency Medicine and Pain Medicine, University of California San Diego, and Vertex Acute Pain Steering Committee Member. “The Phase III safety and efficacy across the three studies are impressive and demonstrate VX 548’s potential to change the paradigm of pain management. 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.”

VX-548 Phase 3 Safety and Effectiveness Study Results: Vertex conducted an additional Phase III study in 256 patients to evaluate safety and effectiveness in a broad range of surgical and non-surgical moderate-to-severe acute pain conditions. Treatment with VX 548 administered orally with an initial dose of 100 mg followed by 50 mg every 12 hours for up to 14 days demonstrated safety, tolerability and effectiveness across these populations. VX 548 was generally safe and well tolerated in this study. AEs were mostly mild or moderate, and there were no SAEs related to VX 548. The safety profile in this study was generally consistent with randomized, controlled Phase III studies with VX 548.

Patient perception of VX 548 effectiveness in treating pain as measured by a patient global assessment (PGA) at the end of treatment showed 83.2% of patients reporting VX 548 as good, very good, or excellent.

Vertex plans to submit a New Drug Application to the FDA by mid-2024 with the goal of achieving a broad label in moderate-to-severe acute pain. VX 548 has secured Breakthrough Therapy and Fast Track designations in the U.S. for acute pain.