nimodipine microparticles (EG-1962) / PDS Biotech - LARVOL DELTA

Efficacy and safety of intraventricular nimodipine in patients with aneurysmal subarachnoid hemorrhage compared to oral nimodipine: a systematic review and meta-analysis. (PubMed, Neurosurg Rev) - "More rigorous research is needed to look at the underlying mechanisms and see if other factors influence the functional outcomes. Clinical trial number Not applicable."

Clinical • Journal • Retrospective data • Review • Cardiovascular • CNS Disorders • Hematological Disorders • Hypotension • Infectious Disease • Subarachnoid Hemorrhage • Ventriculomegaly

Intraventricular Nimodipine vs. Oral Nimodipine in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis (AAN 2024) - "Intraventricular nimodipine demonstrates a marginal risk reduction of angiographic vasospasm but not delayed cerebral ischemia compared with oral nimodipine in patients with aSAH. However, it does not confer additional benefits in terms of eGCS or other adverse events."

Retrospective data • Review • Cardiovascular • Hematological Disorders • Hypotension • Infectious Disease • Subarachnoid Hemorrhage • Ventriculomegaly

Delayed cerebral ischemia and cognitive outcomes after aneurysmal subarachnoid hemorrhage: an exploratory analysis (CNSF 2023) - " We performed a post-hoc analysis of the Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage (NEWTON-2) clinical trial. DCI is a predictor of decreased neuropsychological outcomes in aSAH survivors and may contribute to the morbidity burden in this population."

CNS Disorders • Subarachnoid Hemorrhage

NEWTON-2 Cisternal (Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage): A Phase 2, Multicenter, Randomized, Open-Label Safety Study of Intracisternal EG-1962 in Aneurysmal Subarachnoid Hemorrhage. (PubMed, Neurosurgery) - "Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of EG-1962. Internal carotid artery narrowing and occlusion after placement of EG-1962 in the basal cisterns has not been reported."

Clinical • Journal • P2 data • CNS Disorders • Hematological Disorders • Ischemic stroke • Subarachnoid Hemorrhage

Single-Dose Intraventricular Nimodipine Microparticles Versus Oral Nimodipine for Aneurysmal Subarachnoid Hemorrhage. (PubMed, Stroke) - P3 | "The safety profile was acceptable. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02790632."

Journal • Hematological Disorders • Hypotension • Ischemic stroke • Subarachnoid Hemorrhage

Randomized, Open-Label, Phase 1/2a Study to Determine the Maximum Tolerated Dose of Intraventricular Sustained Release Nimodipine for Subarachnoid Hemorrhage (NEWTON [Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage]). (PubMed) - Stroke - P1/2; "EG-1962 was safe and tolerable to 800 mg, and in this, aneurysmal subarachnoid hemorrhage population was associated with reduced delayed cerebral ischemia and rescue therapy. Overall, the rate of favorable clinical outcome was greater in the EG-1962-treated group."

Journal • Biosimilar • Gene Therapies • Reperfusion Injury

"My latest: Single-Dose Intraventricular Nimodipine Microparticles Versus Oral Nimodipine for Aneurysmal Subarachnoid Hemorrhage | Stroke https://t.co/n8PKpuvuax #SAH @neurocritical #vasospasm" (@stephanamayer)

"Single-Dose Intraventricular Nimodipine Microparticles Versus Oral Nimodipine for Aneurysmal Subarachnoid Hemorrhage #SAH #aSAH #stroke @stephanamayer https://t.co/XhPjih326e" (@StrokeAHA_ASA)

Effect of Locally Delivered Nimodipine Microparticles on Spreading Depolarization in Aneurysmal Subarachnoid Hemorrhage. (PubMed, Neurocrit Care) - "These results are consistent with a beneficial effect of locally delivered nimodipine (EG-1962) on SD after aSAH in more severely injured patients who are at risk of delayed cerebral ischemia related to SD. Larger studies are warranted to test this effect."

Journal

Clinical Trial Protocol: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study Comparing EG-1962 to Standard of Care Oral Nimodipine in Adults with Aneurysmal Subarachnoid Hemorrhage [NEWTON-2 (Nimodipine Microparticles to Enhance Recovery While Reducing TOxicity After SubarachNoid Hemorrhage)]. (PubMed, Neurocrit Care) - P3; "The primary endpoint is the proportion of subjects with favorable outcome (6-8) on the Extended Glasgow Outcome Scale assessed 90 days after aSAH. The secondary endpoint is the proportion of subjects with favorable outcome on the Montreal Cognitive Assessment 90 days after aSAH. Data on safety, rescue therapy, delayed cerebral infarction, and health economics will be collected. Trail registration NCT02790632."

Clinical • Journal • P3 data

Nimodipine pharmacokinetics after intraventricular injection of sustained-release nimodipine for subarachnoid hemorrhage. (PubMed, J Neurosurg) - P1/2; "Plasma concentrations of nimodipine similar to those achieved with oral nimodipine and lasting for 21 days could be achieved after a single intraventricular injection of EG-1962. The CSF concentrations from EG-1962, however, were at least 2 orders of magnitude higher than those with oral nimodipine. These results supported a phase 3 study that demonstrated a favorable safety profile for EG-1962 but yielded inconclusive efficacy results due to notable differences in clinical outcome based on baseline disease severity.Clinical trial registration no.: NCT01893190 (ClinicalTrials.gov)."

Journal • PK/PD data

2016-2017 clinical trials in cerebrovascular neurosurgery. (PubMed, J Clin Neurosci) - "...Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity after Subarachnoid Hemorrhage Trial (NEWTON) and other trials demonstrated no improvement in outcome for vasospasm...Minimally Invasive Surgery plus Alteplase in Intracerebral Hemorrhage Evacuation Trial (MISTIE) reported a new strategy for treating intracerebral hemorrhage...The 10-year results from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) and the new Asymptomatic Carotid Trial I (ACT I) were reported. Lastly, findings from six ischemic stroke trials were presented."

Clinical • Journal

Newton-2: Randomized, Double-blind, Placebo-controlled Study of Eg-1962 in Adults With Aneurysmal Subarachnoid Hemorrhage (ISC 2019) - "Background: EG-1962 is a sustained release microparticle formulation of nimodipine administered via an external ventricular drain (EVD) in patients with aneurysmal subarachnoid hemorrhage (aSAH). This study found no significant improvement in favorable outcome for EG-1962 compared to standard of care in the overall group. Favorable outcome was higher in the prespecified WFNS 3-4 subgroup. The safety profile was acceptable."

Clinical • Late-breaking abstract

"Newton-2: Randomized Double-blind Placebo-controlled Study of Eg-1962 in Adults With Aneurysmal Subarachnoid Hemorrhage" (ISC 2019) - No abstract available.

Clinical • Late-breaking abstract