Suzetrigine
{{Short description|Non-opioid analgesic drug}}
{{Use American English|date=January 2025}}
{{Use dmy dates|date=May 2025}}
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{{Infobox drug
| image = Suzetrigine.svg
| image_class = skin-invert-image
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| image2 = Suzetrigine 3D structure.png
| image_class2 = skin-invert-image
| pronounce = {{IPAc-en|s|u|ˈ|z|ɛ|t|r|ɪ|dʒ|iː|n}}
{{respell|soo|ZE|tri|jeen}}
| tradename = Journavx
| Drugs.com = {{drugs.com|parent|Journavx}}
| MedlinePlus =
| DailyMedID = Suzetrigine
| pregnancy_AU =
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| routes_of_administration = By mouth
| class = Nav1.8 sodium channel blocker; Analgesic
| ATC_prefix = None
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| legal_US = Rx-only
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| CAS_number = 2649467-58-1
| PubChem = 156445116
| IUPHAR_ligand =
| DrugBank = DB18927
| ChemSpiderID = 128942439
| UNII = LOG73M21H5
| KEGG = D12860
| ChEBI =
| ChEMBL = 5314487
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| synonyms = VX-548
| IUPAC_name = 4-
| C = 21
| H = 20
| F = 5
| N = 3
| O = 4
| SMILES = COc1c([C@H]2[C@H](C(=O)Nc3ccnc(C(N)=O)c3)O[C@@](C)(C(F)(F)F)[C@H]2C)ccc(F)c1F
| StdInChI = 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
| StdInChI_comment =
| StdInChIKey = XSQUJFKRXZMOKA-PAFIKIDNSA-N
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Suzetrigine, sold under the brand name Journavx, is a medication used for pain management. It is a non-opioid, small-molecule analgesic that works as a selective inhibitor of Nav1.8-dependent pain-signaling pathways in the peripheral nervous system.{{cite journal | last1=Osteen | first1=Jeremiah D. | last2=Immani | first2=Swapna | last3=Tapley | first3=Tim L. | last4=Indersmitten | first4=Tim | last5=Hurst | first5=Nicole W. | last6=Healey | first6=Tiffany | last7=Aertgeerts | first7=Kathleen | last8=Negulescu | first8=Paul A. | last9=Lechner | first9=Sandra M. |title=Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective NaV1.8 Pain Signal Inhibitor for the Treatment of Moderate to Severe Pain |journal=Pain and Therapy |date=January 2025 |pmid=39775738 |doi=10.1007/s40122-024-00697-0 | doi-access=free | title-link=doi| pmc=11914629 }}{{cite journal |last1=Jones |first1=Jim |last2=Correll |first2=Darin J. |last3=Lechner |first3=Sandra M |last4=Jazic |first4=Ina |last5=Miao |first5=Xiaopeng |last6=Shaw |first6=David |last7=Simard |first7=Christopher |last8=Osteen |first8=Jeremiah D. |last9=Hare |first9=Brian |last10=Beaton |first10=Alina |last11=Bertoch |first11=Todd |last12=Buvanendran |first12=Asokumar |last13=Habib |first13=Ashraf S. |last14=Pizzi |first14=Lois J. |last15=Pollak |first15=Richard A. |last16=Weiner |first16=Scott G. |last17=Bozic |first17=Carmen |last18=Negulescu |first18=Paul |last19=White |first19=Paul F. |title=Selective Inhibition of NaV1.8 with VX-548 for Acute Pain |journal=The New England Journal of Medicine |date=August 2023 |volume=389 |issue=5 |pages=393–405 |doi=10.1056/NEJMoa2209870 |pmid=37530822 |s2cid=260377748 }} It is not addictive. Suzetrigine is taken by mouth.
The most common adverse reactions include itching, muscle spasms, increased blood level of creatine kinase, and rash.
Suzetrigine was developed by Vertex Pharmaceuticals.{{cite press release | title=Vertex Announces Positive Results From the VX-548 Phase 3 Program for the Treatment of Moderate-to-Severe Acute Pain | publisher=Vertex | via=Business Wire | date=30 January 2024 | url=https://www.businesswire.com/news/home/20240129843577/en/ | access-date=31 January 2025 | archive-date=25 December 2024 | archive-url=https://web.archive.org/web/20241225082229/https://www.businesswire.com/news/home/20240129843577/en/ | url-status=live }} It was approved for medical use in the United States in January 2025.{{cite press release|date = 30 January 2025|title = FDA Approves Novel Non-Opioid Treatment for Moderate to Severe Acute Pain|url = https://www.fda.gov/news-events/press-announcements/fda-approves-novel-non-opioid-treatment-moderate-severe-acute-pain|publisher = U.S. Food and Drug Administration (FDA)|access-date = 30 January 2025|archive-date = 7 February 2025|archive-url = https://web.archive.org/web/20250207055306/https://www.fda.gov/news-events/press-announcements/fda-approves-novel-non-opioid-treatment-moderate-severe-acute-pain|url-status = dead}} {{PD-notice}}{{cite web | title=Novel Drug Approvals for 2025 | website=U.S. Food and Drug Administration (FDA) | date=21 February 2025 | url=https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2025 | archive-url=https://web.archive.org/web/20250303200027/https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2025 | url-status=dead | archive-date=3 March 2025 | access-date=9 March 2025}} Suzetrigine is the first medication to be approved by the US Food and Drug Administration (FDA) in this class of medicines.
Medical uses
= Efficacy =
In clinical studies conducted through 2024, suzetrigine reduced pain typically from seven to four on the standard numerical scale used to rate pain. This pain relief matched a combination of hydrocodone and paracetamol (acetaminophen) (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen).{{cite journal |last1=Kingwell |first1=Katie |title=NaV1.8 inhibitor poised to provide opioid-free pain relief |journal=Nature Reviews. Drug Discovery |date=December 2024 |volume=24 |issue=1 |pages=3–5 |doi=10.1038/d41573-024-00203-3 |pmid=39668193 }}
Suzetrigine suppresses pain at the same level as opioids, but without the risks of addiction, sedation, or overdose.{{cite journal |last1=Dolgin |first1=Elie |date=January 2025 |title=US drug agency approves potent painkiller - the first non-opioid in decades |journal=Nature |volume=638 |issue=8050 |pages=304–305 |doi=10.1038/d41586-025-00274-1 |pmid=39885357}}
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. Both trials found that suzetrigine reduced pain more effectively than placebo.
Contraindications
Concomitant use of suzetrigine with strong CYP3A inhibitors is contraindicated.
Adverse effects
Common adverse effects of suzetrigine may include itching, rash, muscle spasms, and increased levels of creatine kinase. Mild side effects may include nausea, constipation, headache, and dizziness.{{cite journal |last1=Hang Kong |first1=Aaron Yik |last2=Tan |first2=Hon Sen |last3=Habib |first3=Ashraf S. |title=VX-548 in the Treatment of Acute Pain |journal=Pain Management |volume=14 |issue=9 |pages=477–486 |date=September 2024 |pmid=39552600 |doi=10.1080/17581869.2024.2421749 |pmc=11721852 |pmc-embargo-date=18 November 2025 }} {{As of|2024|post=,}} long-term safety and side effects remain undetermined.
In preliminary research, suzetrigine had no serious neurological, behavioral, or cardiovascular effects.
Interactions
Consuming grapefruit while using suzetrigine may cause an adverse grapefruit–drug interaction.
Mechanism of action
Suzetrigine operates on peripheral nerves, avoiding the addictive potential of opioids which affect the central nervous system.{{cite magazine |last=Broadfoot |first=Marla |title=New Painkiller Could Bring Relief to Millions — without Addiction Risk |url=https://www.scientificamerican.com/article/new-pain-medication-suzetrigine-prevents-pain-signals-from-reaching-brain/ |access-date=31 January 2025 |magazine=Scientific American |date=20 August 2024 |archive-date=30 December 2024 |archive-url=https://web.archive.org/web/20241230214001/https://www.scientificamerican.com/article/new-pain-medication-suzetrigine-prevents-pain-signals-from-reaching-brain/ |url-status=live }} 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.
In pharmacological studies, suzetrigine selectively inhibited Nav1.8 channels, but not other voltage-gated sodium channels, and bound to a unique site on these sodium channels with a novel allosteric mechanism, by binding to the channel's second voltage sensing domain, thereby stabilizing the closed state, causing tonic inhibition. It exerts its action on dorsal root ganglion.
History
Vertex Pharmaceuticals announced in January 2024 that suzetrigine had successfully met several endpoints in its Phase III clinical trials. The company announced in July 2024 that the FDA had accepted a new drug application for suzetrigine. The FDA granted the application for suzetrigine priority review, fast track, and breakthrough therapy designations.{{cite press release | title=Vertex Announces FDA Acceptance of New Drug Application for Suzetrigine for the Treatment of Moderate-to-Severe Acute Pain | publisher=Vertex | via=Business Wire | date=30 July 2024 | url=https://www.businesswire.com/news/home/20240730731594/en/ | access-date=31 January 2025}} In January 2025, the FDA granted approval of Journavx to Vertex Pharmaceuticals, thereby becoming the first non-opioid pain medication to be approved by the FDA in two decades.
Society and culture
= Legal status =
= Names =
Suzetrigine is the international nonproprietary name.{{cite journal | vauthors = ((World Health Organization)) | year = 2023 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 90 | journal = WHO Drug Information | volume = 37 | issue = 3 | hdl = 10665/373341 | hdl-access = free | author-link = World Health Organization }}
References
{{Reflist}}
Further reading
- {{cite journal | last1=Oliver | first1=Brian | last2=Devitt | first2=Catherine | last3=Park | first3=Grace | last4=Razak | first4=Alina | last5=Liu | first5=Sun Mei | last6=Bergese | first6=Sergio D. | title=Drugs in Development to Manage Acute Pain | journal=Drugs | volume=85 | issue=1 | date=2025 | pmid=39560856 | doi=10.1007/s40265-024-02118-0 | pages=11–19 }}
External links
- {{cite web | title=Suzetrigine (Code C199115) | website=NCI Thesaurus | url=https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C199115 }}
- {{ClinicalTrialsGov|NCT05661734|A Single-arm Study to Evaluate Safety and Effectiveness of VX-548 for Acute Pain}}
- {{ClinicalTrialsGov|NCT05558410|Evaluation of Efficacy and Safety of VX-548 for Acute Pain After an Abdominoplasty}}
{{Analgesics}}
{{Ion channel modulators}}
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Category:Sodium channel blockers
Category:Trifluoromethyl compounds