nerinetide (NA 1) / NoNO - LARVOL DELTA

Opioid-Sparing Effect of Suzetrigine in Total Knee Arthroplasty and Knee Arthroplasty Revision (PAINWeek 2026) - "Generalizability of results is limited by surgeries studied (ie, abdominoplasty and bunionectomy), an inconsistent efficacy benefit compared with hydrocodone-acetaminophen, and a uncertain impact on opioid use...Outcomes evaluated included postoperative opioid prescribing at discharge and prior to the 2-week follow-up appointment (quantified by Morphine Equivalent Daily Dose [MEDD] and total Morphine Milligram Equivalents [MME]), pain control and functional recovery (assessed via pre- and postoperative knee Range of Motion [ROM], Knee injury and Osteoarthritis Outcome Score for Joint Replacement [KOOS JR], and Patient-Reported Outcomes Measurement Information System [PROMIS] scores)...The perioperative standard of care was consistent across the evaluation period; this included an intraoperative “joint cocktail” (bupivacaine, ketorolac, epinephrine +/- clonidine) and a postoperative multimodal regimen of scheduled acetaminophen and NSAID unless contraindicated, in..."

Addiction (Opioid and Alcohol) • CNS Disorders • NAV1

Designing structurally diverse NaV1.8 inhibitors: From screening hit to clinical candidates (ACS-Fall 2026) - "Building on that success, our team then combined knowledge-based design principles, in silico predictions, and high throughput chemistry approaches to design a structurally diverse series of highly selective NaV1.8 inhibitors. Optimization of physicochemical and pharmacological properties led to the invention of a structurally distinct backup clinical candidate."

Clinical • NAV1

Peripherally Selective NaV1.8 Inhibition with Suzetrigine to Facilitate Awake Craniotomy in High‑Risk Patients: A Case Report (ASA 2026) - "Awake craniotomy protocols rely on careful titration of sedative and opioid infusions to facilitate pinning, cranial fixation, surgical exposure, and prolonged positioning; however, they require a delicate balance between providing adequate analgesia while preserving airway patency, ventilation, and neurologic participation during intraoperative mapping. We describe the use of suzetrigine to reduce intraoperative sedative and opioid requirements during awake craniotomy in a high-risk patient while preserving comfort, ventilation, and neurologic participation."

Case report • Clinical • CNS Disorders • Depression • NAV1

Correction to: Safety and Efficacy of Nerinetide at Year in Participants Enrolled in ESCAPE-NEXT: A Multicenter, Double-Blind, Randomized Controlled Trial. (PubMed, J Am Heart Assoc) - No abstract available

Journal

Vertex Lunch and Learn-Exploring Sodium Channel Inhibition for the Management of Acute Pain (AOSSM 2026) - "In this session we will explore the role of NaV1.8 in pain signaling, suzetrigine's mechanism of action, and findings from our clinical studies evaluating suzetrigine. We will then gain clinical insights on the incorporation of its use in practice through discussions on real-world experience with suzetrigine."

Pain • NAV1

Sex differences in brain frailty measures and outcomes after endovascular thrombectomy: ESCAPE-NA1 analysis. (PubMed, J Neurol Sci) - "Although sex-stratified analyses suggested nominal differences, no statistically significant sex-by-brain frailty interactions were observed. Brain frailty should be considered a prognostic marker irrespective of sex, and these exploratory findings warrant further investigation in adequately powered studies."

Journal • Cardiovascular • Ischemic stroke

NMDA Receptor-Targeted Neuroprotection in Ischemic Stroke: The 3S Framework Integrating Spatiotemporal Dynamics, Subtype Selectivity, and Signaling Pathways. (PubMed, Curr Neuropharmacol) - "Translational efforts include subtype-selective antagonists (e.g., NP10679, a pH-sensitive GluN2B inhibitor) and disruptors of pathological protein-protein interactions (e.g., nerinetide, which targets the PSD-95-nNOS interface), while remote ischemic postconditioning has shown encouraging clinical results. Although these mechanisms remain primarily supported by preclinical evidence, they extend the scope of the framework. Collectively, the 3S framework clarifies why complete receptor blockade fails while precision interventions may succeed, and identifies priorities for sex-specific, subtype-targeted neuroprotective strategies in ischemic stroke."

Journal • Cardiovascular • CNS Disorders • Ischemic stroke • ER • GRIN2A • GRIN2B

Safety and Efficacy of Nerinetide at Year 1 in Participants Enrolled in ESCAPE-NEXT: A Multicenter, Double-Blind, Randomized Controlled Trial. (PubMed, J Am Heart Assoc) - P3 | "Long-term benefits of early administration of neuroprotection may emerge up to 1 year after stroke."

Journal • Cardiovascular • Ischemic stroke

Distribution of divalent small interfering RNA into neurons of sensory ganglia produces selective, durable knockdown of Nav1.7 and strong analgesia. (PubMed, Pain) - "Finally, di-siRNA dosed directly at the trigeminal ganglion distributed to most or all cell bodies, reduced Nav1.7 levels, and produced dose-dependent self-lacerating behavior on the head, likely reflecting suppression of pain originating at areas innervated by the trigeminal nerve. The results in male animals show that di-siRNA reduces Nav1.7 in sensory neurons to a level that produces powerful analgesia, showing potential for the di-siRNA modality as a nonopioid analgesic applicable to either systemic or local reduction of pain."

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

Discovery of MK-5661, a Once-Daily Oral NaV1.8 Inhibitor for the Treatment of Pain. (PubMed, ACS Med Chem Lett) - "Optimization of an initial lead, guided by reduction of PXR activation, and dose optimization focusing on half-life and volume ligand efficiency are described. MK-5661 demonstrates a favorable pharmacokinetic profile in preclinical species, as well as efficacy in preclinical models for pain."

Journal • Pain • NAV1

Discovery and Optimization of Potent and Subtype-Selective Urea-Derived NaV1.8 Inhibitors. (PubMed, ACS Med Chem Lett) - "The lead compound 24 exhibited a long in vivo half-life and high exposure (K p,uu) in the pain-relevant target tissue (DRG) in rat PK studies. These findings highlight potential of these compounds for further optimization as nonopioid therapeutics."

Journal • Neuralgia • Pain • NAV1

Efficacy and Safety of Nerinetide in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy Without Thrombolysis: A Meta-analysis of Randomized Trials (AAN 2026) - "However, its efficacy is diminished when co-administered with intravenous thrombolysis (IVT), as alteplase-generated plasmin inactivates nerinetide. Conclusions Nerinetide administration during EVT in AIS patients without IVT did not significantly improve functional independence, survival, or safety outcomes compared to placebo. Although preclinical data supported neuroprotection, clinical benefits were not observed, highlighting the challenges in translating neuroprotective strategies into effective stroke therapies."

Retrospective data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Exploring Sodium Channel Inhibition for the Management of Acute Pain (ASRA-SPRING 2026) - "In this session we will explore the role of NaV1.8 in pain signaling, suzetrigine's mechanism of action, and findings from our clinical studies evaluating suzetrigine. We will then gain clinical insights on the incorporation of its use in practice through discussions on real-world experience with suzetrigine."

Pain • NAV1

MRI measurement of the delayed secondary ischaemic injury following endovascular thrombectomy: results from the REPERFUSE-NA1 study. (PubMed, Eur Stroke J) - P3 | "This study indicates that whole-brain volume loss is a feasible measurement of delayed secondary ischaemic injury. Future neuroprotectant clinical trials could utilise MR-based markers of delayed ischaemic injury."

Clinical • Journal • Cardiovascular • CNS Disorders • Ischemic stroke • Vascular Neurology

Efficacy and Safety of LTG-001, a Selective NaV1.8 Inhibitor, in Patients with Moderate to Severe Pain after Abdominoplasty (AAN 2026) - "Participants were randomized 1:1:1:1 to oral LTG-001 high dose (450mg loading +300mg q12h; n=86), low dose (300mg loading +150mg q12h; n=85), hydrocodone/acetaminophen 5/325mg q6h (opioid reference; n=86), or placebo (n=86) for 48 h; oxycodone 5mg q6h was permitted as rescue... LTG-001 produced rapid, robust analgesia after abdominoplasty with favorable tolerability and significant opioid sparing. Placebo-adjusted 48-hour effect for high-dose LTG-001 (62.1) was the largest of any analgesic tested in abdominoplasty in a published industry-sponsored trial."

Clinical • Aesthetic Medicine • Pain • NAV1

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

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 novel PSD-95 inhibitor BXOS110 provides neuroprotection in acute ischemic stroke. (PubMed, Neuropharmacology) - "In this study, BXOS110 demonstrated a higher binding affinity for PSD-95 than its predecessor, nerinetide (NA-1)...Additionally, we determined that BXOS110 administration must be carefully timed with thrombolytic agents to prevent its degradation, identifying optimal dosing intervals to maximize therapeutic efficacy. These findings highlight the potential of BXOS110 as an integrated stroke therapeutic agent, which combines vascular recanalization with targeted neuroprotection to enhance patient outcomes."

Journal • Cardiovascular • Ischemic stroke • Reperfusion Injury

Efficacy and safety of intravenous nerinetide initiated by paramedics in the field for acute cerebral ischaemia within 3 h of symptom onset (FRONTIER): a phase 2, multicentre, randomised, double-blind, placebo-controlled study. (PubMed, CJEM) - No abstract available

Journal • P2 data

Brain-derived tau for monitoring brain injury in acute ischemic stroke. (PubMed, Sci Transl Med) - "In the biomarker substudy of a phase 3 trial assessing nerinetide in patients with ischemic stroke (N = 193), BD-tau showed predictive performance comparable to the other cohorts, mediated the relationship between recanalization and functional outcome, and showed a 49% smaller increase in the nerinetide group versus placebo. Overall, plasma BD-tau tracked ischemic brain injury over time, outperformed other biomarkers in predicting functional outcomes, and identified possible treatment responses."

Biomarker • Journal • Cardiovascular • CNS Disorders • Ischemic stroke • Vascular Neurology

Therapeutic potential of nerinetide in acute ischemic stroke: a comprehensive systematic review and meta-analysis. (PubMed, Ann Med Surg (Lond)) - "Nerinetide may slightly reduce mortality in AIS, particularly among patients not treated with alteplase. Although functional outcomes did not significantly improve, its favorable safety profile and potential neuroprotective effect support further investigation in larger clinical trials."

Journal • Retrospective data • Cardiovascular • Ischemic stroke

Suzetrigine, a selective NaV1.8 inhibitor in acute and chronic pain: mechanistic insights, clinical outcomes, and future perspectives. (PubMed, Curr Opin Anaesthesiol) - "Suzetrigine represents a promising nonopioid alternative for acute pain and has the potential to fill a significant gap in pain management. While initial results are encouraging, future studies are needed to define its role in chronic pain and multimodal analgesia, and to establish long-term safety."

Clinical data • Journal • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain • NAV1

Efficacy and safety of intravenous nerinetide in acute ischemic stroke patients undergoing endovascular thrombectomy without thrombolysis: a meta-analysis of randomized controlled trials. (PubMed, Neuroradiology) - "Nerinetide administration during EVT in AIS patients without IVT did not significantly improve functional independence, survival, or safety outcomes compared to placebo. Although preclinical data supported neuroprotection, clinical benefits were not observed, highlighting the challenges in translating neuroprotective strategies into effective stroke therapies."

Journal • Retrospective data • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke