Vertex Pharmaceuticals achieved positive results from its Phase 3 program for the selective NaV1.8 inhibitor, VX-548, to treat 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 compared to placebo as well as a clinically meaningful reduction in pain from baseline at 48 hours.
 
For the first key secondary endpoint, Vertex tested the hypothesis that VX-548 was superior to hydrocodone bitartrate/acetaminophen on SPID48 following abdominoplasty surgery or bunionectomy surgery. Neither trial met this key secondary endpoint.
 
The second key secondary endpoint in both trials was time to meaningful pain relief 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.
 
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 with 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.