Suzetrigine

Suzetrigine

Clinical data
Pronunciation	/suˈzɛtrɪdʒiːn/ soo-ZE-tri-jeen
Trade names	Journavx
Other names	VX-548
AHFS/Drugs.com	Journavx
License data	US DailyMed: Suzetrigine
Routes of administration	By mouth
Drug class	Nav1.8 sodium channel blocker; Analgesic
ATC code	None
Legal status
Legal status	US: ℞-only[1]
Identifiers
IUPAC name 4-[[(2R,3S,4S,5R)-3-(3,4-Difluoro-2-methoxyphenyl)-4,5-dimethyl-5-(trifluoromethyl)oxolane-2-carbonyl]amino]pyridine-2-carboxamide
CAS Number	2649467-58-1
PubChem CID	156445116
DrugBank	DB18927
UNII	LOG73M21H5
KEGG	D12860
ChEMBL	ChEMBL5314487
Chemical and physical data
Formula	C21H20F5N3O4
Molar mass	473.400 g·mol^−1
3D model (JSmol)	Interactive image
SMILES CC1C(C(OC1(C)C(F)(F)F)C(=O)NC2=CC(=NC=C2)C(=O)N)C3=C(C(=C(C=C3)F)F)OC
InChI InChI=1S/C21H20F5N3O4/c1-9-14(11-4-5-12(22)15(23)16(11)32-3)17(33-20(9,2)21(24,25)26)19(31)29-10-6-7-28-13(8-10)18(27)30/h4-9,14,17H,1-3H3,(H2,27,30)(H,28,29,31)/t9-,14-,17-,20-/m0/s1 Key:XSQUJFKRXZMOKA-PAFIKIDNSA-N

Suzetrigine, sold under the brand name Journavx, is a medication used for the management of pain.[1][2] It is a non-opioid, small-molecule analgesic that works as a selective inhibitor of Na_v1.8-dependent pain-signaling pathways in the peripheral nervous system,[3][4] avoiding the addictive potential of opioids. Suzetrigine is taken by mouth.[1]

The most common adverse reactions include itching, muscle spasms, increased blood level of creatine kinase, and rash.[1][2]

It was developed by Vertex Pharmaceuticals,[5] and was approved for medical use in the United States in January 2025.[2][6] Suzetrigine is the first medication to be approved by the US Food and Drug Administration (FDA) in this new class of pain management medicines.[2]

Medical uses

Suzetrigine is indicated for the treatment of moderate to severe acute pain in adults.[1][2]

Efficacy

When people used suzetrigine in clinical studies conducted through 2024, there was a reduction in pain typically from seven to four on the standard numerical scale used to rate pain.[7][8] Suzetrigine provided pain relief equal to a combination of hydrocodone and paracetamol (acetaminophen).[8][9]

Suzetrigine suppresses pain at the same level as an opioid, but without the risks of addiction, sedation, or overdose.[10] An alternative to opioids, it is the first pain medication to be approved by the Food and Drug Administration in two decades.[10]

The efficacy of suzetrigine was evaluated in two randomized, double-blind, placebo- and active-controlled trials of acute surgical pain, one following abdominoplasty and the other following bunionectomy.[2] Both trials found that suzetrigine reduced pain more effectively than a placebo.[2]

Contraindications

Concomitant use of suzetrigine with strong CYP3A inhibitors is contraindicated.[1][2]

Adverse effects

Common adverse effects of suzetrigine may include itching, rash, muscle spasms, and increased levels of creatine kinase.[2] Mild side effects may include nausea, constipation, headache, and dizziness.[7][8] As of 2024^[update], long-term safety and side effects remain undetermined.[8]

In preliminary research, suzetrigine had no serious neurological, behavioral, or cardiovascular effects.[3]

Interactions

Consuming grapefruit while using suzetrigine may cause an adverse grapefruit–drug interaction.[1][2]

Mechanism of action

Suzetrigine operates on peripheral nerves, avoiding the addictive potential of opioids which affect the central nervous system.[3][4][7] Unlike opioid medications, which reduce pain signals in the brain, suzetrigine works by closing sodium channels in peripheral nerves, inhibiting pain-signaling nerves from transmitting painful sensations to the brain.[3][4][7]

In pharmacological studies, suzetrigine selectively inhibited Na_v1.8 channels, but not other voltage-gated sodium channels, and bound to a unique site on these sodium channels with a novel allosteric mechanism.[3]

History

Vertex Pharmaceuticals announced in January 2024 that suzetrigine had successfully met several endpoints in its Phase III clinical trials.[5] The company announced in July 2024 that the FDA had accepted a new drug application for suzetrigine.[11] The FDA granted the application for suzetrigine priority review, fast track, and breakthrough therapy designations.[2][11] In January 2025, the FDA granted approval of Journavx to Vertex Pharmaceuticals.[2]

Society and culture

Legal status

Suzetrigine was approved for medical use in the United States in January 2025.[2]

Names

Suzetrigine is the international nonproprietary name.[12]

Suzetrigine is sold under the brand name Journavx.[1][2]

References

1. "Journavx (suzetrigine) tablets, for oral use" (PDF). Vertex Pharmaceuticals. January 2025. Archived (PDF) from the original on 1 February 2025. Retrieved 1 February 2025.
2. "FDA Approves Novel Non-Opioid Treatment for Moderate to Severe Acute Pain" (Press release). U.S. Food and Drug Administration (FDA). 30 January 2025. Archived from the original on 7 February 2025. Retrieved 30 January 2025. This article incorporates text from this source, which is in the public domain.
3. Osteen, Jeremiah D.; Immani, Swapna; Tapley, Tim L.; Indersmitten, Tim; Hurst, Nicole W.; Healey, Tiffany; et al. (January 2025). "Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective NaV1.8 Pain Signal Inhibitor for the Treatment of Moderate to Severe Pain". Pain and Therapy. doi:10.1007/s40122-024-00697-0. PMID 39775738.
4. Jones, Jim; Correll, Darin J.; Lechner, Sandra M; Jazic, Ina; Miao, Xiaopeng; Shaw, David; et al. (August 2023). "Selective Inhibition of NaV1.8 with VX-548 for Acute Pain". The New England Journal of Medicine. 389 (5): 393–405. doi:10.1056/NEJMoa2209870. PMID 37530822. S2CID 260377748.
5. "Vertex Announces Positive Results From the VX-548 Phase 3 Program for the Treatment of Moderate-to-Severe Acute Pain" (Press release). Vertex. 30 January 2024. Archived from the original on 25 December 2024. Retrieved 31 January 2025 – via Business Wire.
6. Constantino, Annika Kim (30 January 2025). "FDA approves Vertex's non-opioid painkiller, first new kind of pain medicine in decades". CNBC. Retrieved 30 January 2025.
7. Broadfoot, Marla (20 August 2024). "New Painkiller Could Bring Relief to Millions — Without Addiction Risk". Scientific American. Archived from the original on 30 December 2024. Retrieved 31 January 2025.
8. Hang Kong, Aaron Yik; Tan, Hon Sen; Habib, Ashraf S. (September 2024). "VX-548 in the treatment of acute pain". Pain Management. 14 (9): 477–486. doi:10.1080/17581869.2024.2421749. PMC 11721852. PMID 39552600.
9. Kingwell, Katie (December 2024). "Na_V1.8 inhibitor poised to provide opioid-free pain relief". Nature Reviews. Drug Discovery. 24 (1): 3–5. doi:10.1038/d41573-024-00203-3. PMID 39668193.
10. Dolgin, Elie (January 2025). "US drug agency approves potent painkiller - the first non-opioid in decades". Nature. doi:10.1038/d41586-025-00274-1. PMID 39885357.
11. "Vertex Announces FDA Acceptance of New Drug Application for Suzetrigine for the Treatment of Moderate-to-Severe Acute Pain" (Press release). Vertex. 30 July 2024. Retrieved 31 January 2025 – via Business Wire.
12. World Health Organization (2023). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 90". WHO Drug Information. 37 (3). hdl:10665/373341.

Further reading

• Oliver, Brian; Devitt, Catherine; Park, Grace; Razak, Alina; Liu, Sun Mei; Bergese, Sergio D. (2025). "Drugs in Development to Manage Acute Pain". Drugs. 85 (1): 11–19. doi:10.1007/s40265-024-02118-0. PMID 39560856.

External links

• "Suzetrigine (Code C199115)". NCI Thesaurus.
• Clinical trial number NCT05661734 for "A Single-arm Study to Evaluate Safety and Effectiveness of VX-548 for Acute Pain" at ClinicalTrials.gov
• Clinical trial number NCT05558410 for "Evaluation of Efficacy and Safety of VX-548 for Acute Pain After an Abdominoplasty" at ClinicalTrials.gov