Journavx (suzetrigine) / Vertex - LARVOL DELTA

Nav1.8 mediates peripheral-to-central nociceptive transmission independently of central presynaptic mechanisms in human DRG-spinal cord circuits. (PubMed, bioRxiv) - "Selective Nav1.8 inhibition with suzetrigine reduced spinal CGRP release only when applied to the DRG or nerve root, not the spinal cord, indicating that Nav1.8 regulates peripheral action potential propagation rather than presynaptic transmitter release. These findings establish the first intact human pain circuit-based assay to study analgesics and demonstrate that the analgesic efficacy of Nav1.8 inhibitors is unlikely to increase with improved CNS penetration."

Journal • Addiction (Opioid and Alcohol) • Pain • NAV1

The Excelsatoxin A-Receptor TMEM233 Modulates Nav1.8. (PubMed, FASEB J) - "ExTxA-induced activation of dorsal root ganglion (DRG) neurons is only partly inhibited by tetrodotoxin (TTX), possibly indicating that the TTX-resistant sodium channel Nav1.8 is also modulated by ExTxA...ExTxA-induced calcium influx in DRG neurons was almost completely inhibited by TTX applied in combination with the selective Nav1.8-inhibitor suzetrigine (VX-548)...Furthermore, TMEM233 seems to be a relevant interacting protein of Nav1.8 that modulates the channel's distinct functional and pharmacological properties. These data warrant further investigations into how TMEM233 regulates nociceptor excitability."

Journal • Anesthesia • Neuroblastoma • Oncology • Pain • Solid Tumor • NAV1

Selective NaV1.8 Inhibition for Pain Management: Current Evidence and Future Potential of Suzetrigine. (PubMed, Curr Pain Headache Rep) - No abstract available

Journal • Review • Pain • NAV1

Suzetrigine for Pain Management: An Observational Study of Early Adoption Patterns. (PubMed, Psychopharmacol Bull) - "Suzetrigine outpatient prescribing has increased significantly over a short time frame at our institution. Continued monitoring of prescription trends, indications, and patient outcomes will be essential as this medication becomes more widely utilized in pain management."

Journal • Observational data • Retrospective data • Pain

Suzetrigine for Non-Mastectomy Breast Surgery (clinicaltrials.gov) - P4 | N=120 | Not yet recruiting | Sponsor: University of California, San Diego

New P4 trial • Pain

Novel drugs approved by the EMA, the FDA and the MHRA in 2025: A year in review. (PubMed, Br J Pharmacol) - "Among the FIC drugs, it is worth mentioning the Nav1.8 channel inhibitor suzetrigine, the first non-opioid approved to palliate acute pain; the first positive allosteric modulator of transient receptor potential melastatin 8 (TRPM8), acoltremon, that increases basal tear production in dry eye disease, a globally common disorder; lerodalcibep, a 'third generation' adnectin inhibitor of the protease Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) to treat elevated LDL-c; and zoliflodacin and gepotidacin, both innovatively targeting bacterial topoisomerases to treat uncomplicated urinary tract infections. These approaches include: the combination of two FIC drugs, the RAF/MEK clamp avutometinib paired with the FAK/Pyk2 inhibitor defactinib, to block more efficiently the RAS-RAF-MEK-ERK/FAK oncogenic pathway in low-grade serous ovarian cancer; fitusiran, the first RNAi therapy for haemophilia, targeting for the first time the production of the natural..."

European regulatory • FDA event • Journal • Review • Bronchiectasis • Dry Eye Disease • Hematological Disorders • Hemophilia • Infectious Disease • Nephrology • Oncology • Ophthalmology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pain • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Solid Tumor • NAV1 • TRPM8

Suzetrigine (VX-548) exhibits activity-dependent effects on human dorsal root ganglion neurons with differential pain etiology. (PubMed, Pain) - "In contrast, suppression of discharges evoked by intracellular current injection was moderate. These results suggest that suzetrigine will likely show efficacy vs spontaneous pain but may have less robust effects on evoked or breakthrough pain."

Journal • Cardiovascular • Neuralgia • Pain • NAV1

Suzetrigine (a NaV1.8 inhibitor) versus placebo for acute postoperative pain: A systematic review and meta-analysis of randomized controlled trials. (PubMed, Medicine (Baltimore)) - "Suzetrigine produced modest reductions in pain at 24 to 48 hours versus placebo. Because opioid consumption was not consistently reported, no conclusions can be drawn regarding opioid-sparing."

Clinical • Journal • Retrospective data • Review • Aesthetic Medicine • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain • NAV1

Safety and efficacy of Suzetrigine (VX-548) for acute moderate to severe pain in adults; a systematic review and meta-analysis. (PubMed, J Clin Anesth) - "Suzetrigine was better tolerated and more efficacious than placebo making it a promising medication for moderate to severe acute pain treatment in adults."

Journal • Retrospective data • Review • Addiction (Opioid and Alcohol) • Pain • Thermal Injury • NAV1

KHN702, a Novel Selective hNav1.8 Inhibitor for Pain Therapy (AAN 2026) - "When compared to VX-548 in head-to-head comparative studies, KHN702 showed compelling advantages including superior pharmacokinetic profiles in rat and monkey, faster on set of action and better analgesic effects in acute and chronic pain models as well as higher safety windows... Nav1.8 represents a novel and non-addictive target for the treatment of pain. KHN702 demonstrated favorable efficacy and safety profile which is currently undergoing phase I study (CTR20252159). The preliminary results show that KHN702 is safe and well-tolerated, no serious or severe AEs were observed."

Addiction (Opioid and Alcohol) • Musculoskeletal Pain • Neuralgia • Pain • NAV1

Suzetrigine as Part of Multimodal Therapy (MMT) Enables Opioid-free Recovery After Aesthetic and Reconstructive Surgery (PainConnect 2026) - No abstract available

Surgery

Nine-months Post-launch Suzetrigine Utilization Patterns in Real-World Settings (PainConnect 2026) - No abstract available

Clinical • Real-world • Real-world evidence

Suzetrigine for Chronic Left Upper Extremity Pain in a Patient with Spinal Cord Injury on a High-Dose Multimodal Pain Regimen05. (PainConnect 2026) - No abstract available

Clinical • CNS Disorders • Orthopedics • Pain

Suzetrigine as Part of Multimodal Therapy (MMT) Enables Opioid-free Recovery After Aesthetic and Reconstructive Surgery (PainConnect 2026) - No abstract available

Surgery

Suzetrigine: Acute Pain (PainConnect 2026) - No abstract available

Pain

Reflections on suzetrigine and the evolving landscape of non-opioid analgesia. (PubMed, Br J Pain) - No abstract available

Journal

Clinical and methodological uncertainty in the economic evaluation of suzetrigine. (PubMed, J Med Econ) - No abstract available

HEOR • Journal

Reply: clinical and methodological uncertainty in the economic evaluation of suzetrigine. (PubMed, J Med Econ) - No abstract available

HEOR • Journal

Suzetrigine for Acute Pain in the Emergency Department: A First-in-Class NaV1.8 Blocker. (PubMed, J Am Coll Emerg Physicians Open) - "In 3 phase 3 studies of patients with acute pain, mostly from surgical causes, suzetrigine produced clinically meaningful reductions in 48-hour pain scores vs placebo and analgesia equivalent to hydrocodone/acetaminophen...Studies of suzetrigine's use in the ED for nonsurgical pain must be conducted to ensure proper utilization. However, suzetrigine's oral formulation, preliminary favorable safety profile, and apparent lack of addictive potential based on early-stage trials align well with contemporary ED guidelines that prioritize multimodal, opioid-sparing analgesia, making it a promising addition to the armamentarium for pain management in the ED."

Clinical • Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Pain • Psychiatry • NAV1

Evaluation of the Excretion of Suzetrigine Into Breast Milk in Healthy Lactating Female Participants (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Pain

Prevalence of Halogens in 2025 FDA-Approved Drugs: Highlight on Suzetrigine, the First Nonopioid Painkiller in Decades. (PubMed, J Med Chem) - No abstract available

FDA event • Journal • Pain

Suzetrigine: A New Non-Opioid Analgesic Option With Potential Implications for Serious Illness Care. (PubMed, J Palliat Care) - "While clinical trials demonstrate its noninferiority to hydrocodone/acetaminophen in acute postsurgical settings, the authors highlight significant barriers to its use in palliative and hospice care. These limitations include a lack of evidence in patients with serious illness, a current safety restriction of 14 days of use, and a high cost of approximately $15.50 per tablet. Consequently, while suzetrigine represents a significant pharmacological advancement, its current utility is likely limited to short-term acute pain crises until further data support its long-term application in serious illness management."

Journal • Anesthesia • CNS Disorders • Depression • Oncology • Pain • Palliative care • Psychiatry • NAV1

Selective Nav1.8 inhibition by suzetrigine, a novel nonopioid analgesic for acute pain management: A systematic review and metanalysis. (PubMed, Saudi J Anaesth) - "Suzetrigine appears to be an effective, well-tolerated option for acute pain management, showing superiority to placebo and comparable efficacy to HB/APAP, with a better safety profile. However, future long-term studies are needed to assess its efficacy and safety in various acute pain settings."

Journal • Pain • NAV1

Suzetrigine, a novel nonopioid analgesic for acute pain. (PubMed, Curr Opin Anaesthesiol) - "Suzetrigine shows significant potential to improve the treatment of moderate-to-severe acute pain of both surgical and nonsurgical origin."

Journal • Addiction (Opioid and Alcohol) • Pain • NAV1

The Clinical Application of Suzetrigine. (PubMed, J Pain Palliat Care Pharmacother) - "As a new type of analgesic, the clinical studies of suzetrigine in other types of pain and special populations, as well as whether there are gender metabolic differences, are still unknown. Thus, current research on suzetrigine is worth further exploration."

Journal • Review • Aesthetic Medicine • Pain • Renal Disease • NAV1