The New England Journal of MedicineSelective Inhibition of Na(V)1.8 with VX-548 for Acute Pain

Selective inhibition of the Na_V1.8 voltage-gated sodium channel has been a topic of interest in pain management. The study delves into the efficacy and safety of VX-548, a selective inhibitor of Na_V1.8, in managing acute pain post-surgery.

Study Design

• Investigated the selectivity of VX-548 for Na_V1.8 inhibition in vitro.
• Two phase 2 trials conducted: one post-abdominoplasty and the other post-bunionectomy.
• Abdominoplasty trial: 303 participants, four treatment groups (high-dose VX-548, middle-dose VX-548, hydrocodone bitartrate–acetaminophen, and placebo).
• Bunionectomy trial: 274 participants, five treatment groups (high-dose, middle-dose, low-dose VX-548, hydrocodone bitartrate–acetaminophen, and placebo).
• Primary end point: time-weighted sum of the pain-intensity difference (SPID48) over 48 hours.

Key Findings

• High-dose VX-548 showed a significant difference in SPID48 compared to placebo: 37.8 (95% CI, 9.2 to 66.4) post-abdominoplasty and 36.8 (95% CI, 4.6 to 69.0) post-bunionectomy.
• Lower doses of VX-548 yielded results comparable to placebo.
• Common adverse events: headache and constipation.

Conclusion

• High-dose VX-548 effectively reduced acute pain over 48 hours post-abdominoplasty or bunionectomy compared to placebo.
• Adverse events linked to VX-548 were mild to moderate.

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Did You Know?
The Na_V1.8 voltage-gated sodium channel plays a crucial role in transmitting nociceptive signals, which are central to pain perception.