Vertex Pharmaceuticals Incorporated announced that it has begun a Phase 2 proof-of-concept (POC) study in acute pain following bunionectomy surgery with the selectiveNaV1.8 inhibitor VX-548 and that it expects to commence a second Phase 2 study in acute pain following abdominoplasty surgery in the coming weeks. The Phase 2 studies are randomized, double-blind, placebo-controlled trials that will evaluate multiple doses of VX-548 in patients with acute pain following bunionectomy surgery or abdominoplasty surgery. Both studies will also include a hydrocodone bitartrate /acetaminophen reference arm. The primary endpoint in both studies is the time-weighted Sum of the Pain Intensity Difference over the first 48 hours of treatment (SPID48). VX-548 is an oral, selective NaV1.8 inhibitor that has completed Phase 1 studies in healthy volunteers. Based on a favorable pharmacokinetic, safety and tolerability profile, it was advanced to Phase 2 studies in 2021. NaV1.8 is a voltage-gated sodium channel that plays a critical role in pain signaling in the peripheral nervous system. NaV1.8 is a genetically validated novel target for the treatment of pain, and Vertex has previously demonstrated clinical proof-of-concept with a small molecule investigational treatment targeting NaV1.8 in multiple pain indications including acute pain, neuropathic pain and musculoskeletal pain. Vertex’s approach is to selectively inhibit NaV1.8 using small molecules with the objective of creating a new class of medicines that have the potential to provide superior relief of acute pain without the limitations of opioids, including their addictive potential. VX-548 is the most recent molecule to enter clinical development from Vertex’s portfolio of NaV1.8 inhibitors.