Vertex Pharmaceuticals Incorporated announced positive results from its Phase 3 program for the selective NaV1.8 inhibitor, VX-548, in the treatment of moderate-to-severe acute pain. The Phase 3 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 ≥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 3 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 3 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 3 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.”