High doses of VX-548 reduced acute pain over a period of 48 hours after major surgery: NEJM

A recent study has found effective acute pain management with VX-548, an oral, highly selective inhibitor targeting the NaV1.8 voltage-gated sodium channel expressed in peripheral nociceptive neurons. The findings were published in the The New England Journal of Medicine.

The NaV1.8 voltage-gated sodium channel has long been recognized as a key player in transmitting nociceptive signals, making it a promising target for acute pain relief. Jim Jones and team established VX-548's selectivity for NaV1.8 inhibition through rigorous in vitro studies.

Two separate phase 2 trials were conducted to evaluate VX-548's efficacy in acute pain management after abdominoplasty and bunionectomy surgeries. The trials involved a total of 303 participants for abdominoplasty and 274 participants for bunionectomy, respectively.

During the abdominoplasty trial, participants were randomly assigned to one of four groups: a high-dose group receiving a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours; a middle-dose group receiving a 60-mg loading dose, followed by a 30-mg maintenance dose every 12 hours; a hydrocodone bitartrate–acetaminophen group receiving 5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours; or an oral placebo every 6 hours. Similarly, the bunionectomy trial had five groups with various VX-548 dosages and a placebo.