suzetrigine

suzetrigine, pain-relieving drug, the first to be developed in a class of agents known as non-opioid analgesics, named for the ability to provide pain relief without the risk of addiction associated with the use of opioid medications. Suzetrigine was designed specifically for adults with moderate to severe acute pain; it was approved by the U.S. Food and Drug Administration (FDA) in 2025. It is marketed under the brand name Journavx.

Development

Suzetrigine was developed by the U.S.-based biotech company Vertex Pharmaceuticals; it initially was known as VX-548. In 2022 the drug was investigated in a Phase 2 clinical trial; this proof-of-concept study in humans demonstrated its promise for the treatment of acute pain. A Phase 3 trial in 2024 showed that VX-548 effectively and safely reduced acute pain after abdominal and foot surgery. The drug subsequently received breakthrough therapy, fast-track, and priority review designations from the FDA, which sped up its approval and arrival on the market. Its approval in 2025 marked the introduction of the first new class of pain management medicines in more than 20 years.

Mechanism of action

Suzetrigine functions as a highly selective inhibitor of a voltage-gated sodium channel known as NaV1.8, which occurs on the surface of nociceptors (pain-sensing neurons) in the peripheral nervous system, particularly dorsal root ganglion (DRG) neurons. DRG neurons convey pain signals to the spinal cord and brain. In the transmission of these signals, NaV1.8 opens to allow positively charged sodium ions to enter the cell. As the membrane in the immediate area becomes less negative, a depolarization effect occurs, producing a wave of change in electric charge distribution that moves the impulse along the neuron (see action potential).

NaV1.8 contains four distinct voltage-sensing domains (VSD1–VSD4), each with four transmembrane segments, designated S1 through S4, that detect changes in membrane potential and channel activation. Suzetrigine binds specifically to the extracellular loop between S3 and S4 within VSD2, where it stabilizes the channel in its closed state. This inhibitory effect prevents the channel from opening in response to voltage changes and reduces pain signal propagation.

Administration and side effects

Suzetrigine is taken orally, with an initial dose followed by maintenance doses every 12 hours. Possible side effects include itching, muscle spasms, rash, and elevated blood levels of creatine phosphokinase (creatine kinase), which is found in tissue in the heart, brain, and skeletal system. Because NaV1.8 is present only in the periphery, suzetrigine is said to provide pain relief without affecting the central nervous system, which reduces the risk of addiction and other central side effects commonly associated with opioid analgesics.