nerinetide (NA 1) / NoNO - LARVOL DELTA

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. 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

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

Efficacy and Safety of Nerinetide in Acute Ischemic Stroke Patients: A Systematic Review, Meta-Analysis and Meta Regression. (PubMed, Brain Behav) - "Nerinetide may modestly reduce mortality in AIS without increasing adverse events but does not significantly improve the functional outcomes. The benefits may be greater in patients who do not receive thrombolysis. Further large-scale trials are warranted to clarify the optimal use and interactions with reperfusion therapies."

Journal • Retrospective data • Review • Atrial Fibrillation • Cardiovascular • CNS Disorders • Epilepsy • Hypotension • Ischemic stroke • Vascular Neurology

Development of a novel cyclotide to target neuronal excitotoxicity (Neuroscience 2025) - "This signalling cascade can be blocked using a therapeutic peptide known as Nerinetide or NR2b9c...Further, administration of c5R-NR2B9c in a mouse model of epilepsy resulted in increased survival and reduced seizure severity after seizure induction. Overall, we show that modifying cyclotides can enhance delivery of therapeutic peptides into neuronal cells, which can be utilized to protect neurons from excitotoxicity."

Alzheimer's Disease • CNS Disorders • Dementia • Epilepsy

ANG2B9C: A NOVEL NEUROPROTECTIVE PSD-95 INHIBITOR WITHOUT HISTAMINE-RELATED SIDE EFFECTS (WSC 2025) - "ConclusionsANG2B9c is a promising neuroprotective candidate that retains the efficacy of nerinetide while eliminating histamine-related adverse effects. Its improved safety profile supports its potential for prehospital stroke treatment and broader clinical use."

Adverse events • Cardiovascular • CNS Disorders • Hypotension • Vascular Neurology • GRIN2B

Targeting Nav1.8 with the nonopioid antagonist suzetrigine in analgesia. Comment on Br J Anaesth 2025; 135: 829-32. (PubMed, Br J Anaesth) - No abstract available

Journal • Neuralgia • Pain • NAV1

Targeting excitotoxicity in acute stroke: hope or hype. (PubMed, Cardiovasc Res) - No abstract available

Journal • Cardiovascular

ENA1, a transporter of nicotianamine that mediates secretion in the root of Arabidopsis. (PubMed, New Phytol) - "Its species-specific regulation and localization suggest an adaptive mechanism for rhizosphere metal management. This discovery advances our understanding of plant metal homeostasis and provides a molecular basis for phytoremediation and biofortification strategies."

Journal

Suzetrigine: A novel selective sodium channel inhibitor for pain. (PubMed, Am J Health Syst Pharm) - "Suzetrigine represents an advancement in pain management as a nonopioid alternative for pain with potentially lower abuse risk and potentially fewer serious adverse effects when compared to opioids. While initial results are promising, further research is needed to establish its long-term safety and efficacy for various painful conditions. Research will continue in the area of analgesics that selectivity inhibit peripheral sodium channels."

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

Neuroprotective Agents With Reperfusion Therapies in Ischemic Stroke: Evidence From Recent Randomized Trials. (PubMed, Cureus) - "Interventions included nerinetide, edaravone (and its derivatives), nelonemdaz, cerebrolysin, minocycline, glyceryl trinitrate, and normobaric hyperoxia. Quality assessment using the Cochrane Risk of Bias (RoB) 2.0 tool revealed low to moderate risk of bias across most studies. Although the evidence remains heterogeneous, this review highlights the potential role of neuroprotective agents as adjuncts to reperfusion therapy and identifies promising directions for future clinical trials."

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

Targeting Nav1.8 with the nonopioid antagonist suzetrigine in analgesia: cause for optimism? (PubMed, Br J Anaesth) - "Recent large trials have shown some efficacy of the new Nav1.8 allosteric inhibitor suzetrigine in acute postoperative pain, and ongoing studies are investigating its potential for painful diabetic neuropathy. If efficacy is confirmed, this type of drug might fill a significant gap in the treatment of acute and chronic pain, offering a safer alternative to opioids and marking the advent of a new class of nonopioid analgesics."

Journal • Diabetic Neuropathy • Neuralgia • Pain • NAV1

Tat-NR2B9c prevent cognitive dysfunction in mice modeling Alzheimer's Disease induced by Aβ1-42 via perturbing PSD-95 interactions with NR2B-subtype receptors. (PubMed, IBRO Neurosci Rep) - "Tat-NR2B9c can improve spatial learning and memory ability in AD mice by perturbing PSD-95 interactions with NR2B-subtype but not inhibiting PSD-95 levels. Tat-NR2B9c can prevent cognitive dysfunction in mice modeling AD induced by Aβ1-42 via perturbing PSD-95 interactions with NR2B-subtype receptors."

Journal • Preclinical • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Neuralgia • Pain

Incidence, Associations, and Mechanisms of Unexplained Early Neurologic Deterioration After Thrombectomy in Stroke Patients. (PubMed, Neurology) - "UnEND occurred in approximately 10% of large vessel occlusion thrombectomy patients and was associated with older age, longer onset-to-reperfusion time, and anesthesia use. Patients who experienced IEBP, that is, 24-hour infarct volume extension beyond the initial hypoperfused tissue, were 7 times more likely to develop unEND."

Clinical • Journal • Anesthesia • Cardiovascular • Hematological Disorders • Ischemic stroke

Uncoupling toxic NO signaling: Progress, challenges, and therapeutic promise of disrupting the PSD-95/nNOS protein-protein interaction. (PubMed, Eur J Med Chem) - "Over the past two decades, cell-penetrant peptides such as nerinetide (Tat-NR2B9c) have validated the target from rodent stroke models to phase-III clinical trials, while bivalent constructs achieve low-nanomolar affinity and extended brain exposure. Parallel medicinal-chemistry campaigns have delivered multiple small-molecule scaffolds (IC87201, ZL006, SCR-4026, PCC-0105002) that cross the blood-brain barrier, disrupt the complex at low-micromolar concentrations, and demonstrate efficacy in ischemic stroke, neuropathic pain, and neuropsychiatric paradigms without the liabilities of NMDAR antagonists...Structural elucidation of ligand-bound complexes, covalent and bivalent chemistries, and AI-guided design promise to surmount these hurdles. Collectively, the evidence positions PSD-95/nNOS disruption as a versatile, clinically achievable approach for mitigating excitotoxic and nociceptive pathology and sets the stage for first-in-class therapies that uncouple toxic NO..."

Journal • Review • Cardiovascular • Ischemic stroke • Neuralgia • Pain • Psychiatry

Association between Time and Severe Hypoperfusion with Risk of Hemorrhagic Transformation in Stroke Patients. (PubMed, Int J Stroke) - "Both severe hypoperfusion and time affect the risk of hemorrhagic transformation. However, the interaction between these two variables was not statistically significant, indicating that their effects on hemorrhagic transformation risk are not dependent on each other. Analyzing these variables may help identify patients with a leaky, severely compromised blood-brain barrier in the ischemic core-a "leaky core."."

Journal • Cardiovascular • Hematological Disorders • Ischemic stroke