Radicava (edaravone) / Tanabe Pharma - LARVOL DELTA

Exploratory Post Hoc Analysis of Neutrophil-to-lymphocyte Ratio as a Novel Response Biomarker for Edaravone Oral Suspension-treated Patients with Amyotrophic Lateral Sclerosis vs Untreated Propensity Score-matched PRO-ACT Historical Placebo Controls (AAN 2026) - P3 | "Objective: Assess Neutrophil-to-Lymphocyte Ratio (NLR) response to edaravone oral suspension treatment in patients with amyotrophic lateral sclerosis (ALS) and whether baseline NLR may predict NLR response vs propensity score-matched Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) placebo controls.Background: The US Food and Drug Administration (FDA) approved an on/off dosing regimen of Radicava ORS® (edaravone) oral suspension for patients with ALS...MT-1186-A01/A02/A03/A04 patients were propensity score-matched 1:1 on 11 baseline variables with historical, PRO-ACT controls (patients given placebo may have received riluzole)... Edaravone oral suspension treatment in MT-1186 studies vs PRO-ACT controls supports the possible role of NLR as a novel ALS prognostic biomarker. These analyses were non-randomized comparisons, and there was a potential time bias between matched groups. Further studies are needed to validate NLR as a prognostic biomarker..."

Biomarker • Clinical • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

Introduction to the Supplement. (PubMed, Muscle Nerve) - "Three active pharmaceutical agents are currently approved by the United States Food and Drug Administration (FDA) for ALS: riluzole, edaravone (including intravenous [IV] and oral suspension formulations), and tofersen. Study MCI186-19 (Study 19) was a pivotal, phase 3 randomized controlled trial that demonstrated a significant reduction in physical functional decline vs. placebo in Japanese patients with ALS and contributed to FDA approval of IV edaravone in 2017...Topics include safety in clinical practice, generalizability of efficacy, clinical treatment outcomes, and health economics and outcomes research studies. Together, these findings aim to inform clinicians, researchers, and stakeholders regarding the evolving evidence base for edaravone in the management of ALS."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Survival of Intravenous Edaravone-Treated Patients With ALS: Evidence From Administrative Claims Analyses. (PubMed, Muscle Nerve) - "Median overall survival was 29.5 versus 23.5 months for the edaravone-treated group compared to controls, with a 27% reduced risk of death observed in the treated cohort (p = 0.005). These findings, together with existing data from the pivotal phase 3 Study MCI186-19 of IV edaravone, contribute to the growing body of literature suggesting a dual benefit of edaravone on both function and survival in ALS, offering critical insights for clinicians, patients, and payers navigating ALS treatment decisions."

Journal • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

Generalizability of Edaravone Efficacy. (PubMed, Muscle Nerve) - "The pivotal phase 3 trial MCI186-19 (Study 19) demonstrated the efficacy of intravenous edaravone in slowing functional decline in patients with amyotrophic lateral sclerosis (ALS), leading to United States Food and Drug Administration approval...Both high- and low-FVC subgroups demonstrated reduced ALS functional rating scale-revised decline at 48 weeks when treated continuously with edaravone. These findings support the potential benefit of edaravone in a wider range of patients with ALS than those enrolled in Study 19, providing important insights into how clinical trial enrichment strategies may influence perceived efficacy, and underscoring the need for future prospective studies in more diverse ALS populations."

Journal • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

Study 19 (MCI186-19) Post Hoc Analyses. (PubMed, Muscle Nerve) - "Collectively, these findings reinforce the long-term clinical benefit of edaravone and demonstrate that edaravone may offer benefits across a spectrum of ALS disease trajectories, beyond those defined in the original study criteria. These studies help address questions not captured in the original RCT and may inform future trial design and treatment decisions."

Journal • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

Safety and Pharmacokinetics of MCI-186 in Subjects With Acute Ischemic Stroke (clinicaltrials.gov) - P2 | N=36 | Completed | Sponsor: Tanabe Pharma Corporation | Phase classification: P2a ➔ P2

Phase classification • Cardiovascular • Ischemic stroke

Shionogi Expands Rare Disease Presence with Planned Acquisition of Global Rights to Tanabe Pharma Corporation’s RADICAVA ORS (edaravone) and IV RADICAVA (Businesswire) - "Tanabe Pharma plans to form this new entity, and Shionogi intends to purchase 100% of its shares. The agreement between Shionogi and Tanabe Pharma was signed this afternoon. As part of the transaction, a new business company established by Tanabe for RADICAVA in the U.S. will become a wholly owned subsidiary of Shionogi Inc....Under this agreement, Shionogi will pay a lump sum of USD 2.5 billion to Tanabe Pharma through Shionogi Inc., upon completion of the procedures. Additionally, Shionogi may pay a royalty on future sales, subject to certain conditions."

M&A • Amyotrophic Lateral Sclerosis

Tanabe Pharma America to Present Preclinical Research at MNDA on Edaravone's Potential Mechanisms in ALS (PRNewswire) - "...Treatment with edaravone was observed to preserve neurite structures and reduce neuronal cell death in ALS iPSNs in a concentration-dependent manner, whereas the control treatment (vitamin C) did not produce similar effects. Edaravone also reduced indicators of oxidative stress and was associated with changes in TDP-43 localization."

Preclinical • Amyotrophic Lateral Sclerosis

Real-world data on disease-modifying drugs for ALS in Japan (ALS-MND 2025) - "Edaravone was previously administered as an intravenous injection, but on 17 April 2023, Radicut oral suspension was launched (the U.S. product name, RADICAVA ORSV, was approved in the U.S. in May 2022 and in Canada in November)... The 10th NDB Open Data covers the period including the launch of Edaravone oral suspension, and compares the number of prescriptions before and after the launch of Edaravone oral suspension. After the launch of Edaravone oral suspension, the number of prescriptions increased every month, while the number of outpatient prescriptions for Edaravone injection decreased. The number of prescriptions for Riluzole also gradually decreased."

Clinical • Real-world • Real-world evidence

Exploratory post hoc analysis of neutrophil-tolymphocyte ratio as a novel responsiveness biomarker for edaravone oral suspension–treated patients with amyotrophic lateral sclerosis vs untreated propensity score–matched PRO-ACT historical placebo controls (ALS-MND 2025) - P3 | "Sponsorship: Study sponsored by Mitsubishi Tanabe Pharma America, Inc., Jersey City, NJ, USA..Background: The US Food and Drug Administration (FDA) approved an on/off dosing regimen of Radicava ORSV(edaravone) oral suspension for patients with amyotrophic lateral sclerosis (ALS)...Study MT-1186-A01/A02/A03/A04 patients were propensity score matched 1:1 on 11 baseline variables with historical, PRO-ACT controls (placebo-arm participants not administered investigational treatment but may have received riluzole)... Relative to baseline NLR, patients from Studies MT-1186-A01/02/03/04 (n = 221) showed a numeric trend toward suppressing NLR at 48 weeks (least squares mean difference= −0.2851) vs. matched PRO-ACT controls (n = 221) (p = 0.065). Patients were grouped according to baseline NLR <3 or NLR ≥3."

Biomarker • Clinical • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

At-home telespirometry identifies significantly slower decline of ALS functional rating scale-revised total score but not erect/supine slow vital capacity in edaravone-treated ALS subjects not requiring noninvasive ventilation [NCT05106569] (ALS-MND 2025) - P=N/A | "There was no statistically significant effect of IV edaravone or edaravone oral suspension on the: (1) mean delta eSVC/sSVC overall or according to NIV treatment status (2) mean delta ALSFRS-R total score overall. Analysis according to NIV treatment status identified a statistically significant (p = 0.037) slowing in the mean delta ALSFRS-R total score (−0.9 units/month [Q1, Q3= −1.2, −0.4]) in edaravone-treated subjects vs mean delta ALSFRS-R total score (−1.5 units/ month [Q1, Q3= −2.1, −0.8]) in ALS subjects not treated with edaravone that did not use NIV during the study. Strengths include number of subjects uniformly studied, higher ALSFRS-R progression rate compared with certain published rates, and NIV treatment initiation stratification."

Clinical • Non-invasive

Acceptance of Clinical Studies Conducted in Nonus Settings by the FDA Based on the Analysis of Selected Novel Drug Approvals (ISPOR-EU 2025) - "In 2017, only 2 (4%) novel drugs met the criterion, including Radicava, evaluated exclusively in Japan with no US patient representation... Cases show an increasing rate of products accepted based on foreign data. If studies are conducted under Good Clinical Practice (GCP) and there are no significant regional or ethnic differences in outcomes, they could be accepted without further requirements. However, sometimes post-marketing studies are needed, and recent US policy changes could increase the FDA's foreign data scrutiny."

Clinical

Edaravone for amyotrophic lateral sclerosis. (PubMed, Aust Prescr) - No abstract available

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders

EVALUATION OF LONG-TERM PROGNOSIS OF EDARAVONE IN ALS PATIENTS: A REAL-WORLD COMPARATIVE STUDY USING SUNRISE JAPAN AND JACALS REGISTRY DATA (PACTALS 2025) - "Additionally, comparisons were conducted within patient populations comparable to those in the clinical trial MCI186-19... This investigation, which examines the long- term prognostic impact of edaravone under real- world conditions using existing registry data from JaCALS, may provide a valuable reference for studies on other neurodegenerative diseases."

Clinical • Real-world • Real-world evidence • Amyotrophic Lateral Sclerosis • CNS Disorders

CLINICAL TRIAL OF BOSUTINIB FOR AMYOTROPHIC LATERAL SCLEROSIS: IDREAM STUDY (PACTALS 2025) - "Efficacy was assessed with the total ALSFRS-R compared to the placebo arm or edaravone arm in edaravone Study MCI186- 19 and with ALS registry data from JaCALS. This is a Phase 2 open-label clinical trial. No new safety concerns were identified in the 24-week bosutinib treatment of patients with ALS. Three out of four efficacy endpoints were met in the efficacy analysis."

Clinical • Amyotrophic Lateral Sclerosis • Chronic Myeloid Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • ABL1

ALS Treatment Update RADICAVA (PACTALS 2025) - "Sponsored by Teva Pharma Australia"

Real-world safety and tolerability of intravenous edaravone in patients with amyotrophic lateral sclerosis. (PubMed, Neurodegener Dis Manag) - "Treatment discontinuation was primarily related to ALS disease progression/death, rather than safety or tolerability. This study representative of real-world patients with ALS suggests that edaravone showed consistent safety and tolerability profiles with previous studies."

Journal • Real-world evidence • Amyotrophic Lateral Sclerosis • CNS Disorders

Development and Validation of a Stability-Indicating RP-HPLC Method for Edaravone Quantification. (PubMed, Molecules) - "Currently, it is available as an IV infusion (Radicava®, Jersey City, NJ, USA) and an oral liquid suspension (Radicava ORS®, Jersey City, NJ, USA)...Successful separation of edaravone from void signals and degradant products was achieved. The method was precise and accurate at the concentration range of 6.8-68.6 µg/mL and was recommended to use without methyl hydroxybenzoate (MHB) as an internal standard."

Journal • Amyotrophic Lateral Sclerosis

Analysis of Long-Term Function and Survival of Edaravone Oral Suspension-Treated Patients With Amyotrophic Lateral Sclerosis Using PRO-ACT Data as Historical Placebo Controls. (PubMed, Muscle Nerve) - "This suggests edaravone oral suspension significantly increases survival time and decreases physical functional decline versus PRO-ACT placebo patients."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Safety Extension Study of Edaravone Oral Suspension in Patients With Amyotrophic Lateral Sclerosis for up to an Additional 96 Weeks of Treatment. (PubMed, Muscle Nerve) - P3 | "These results help establish the long-term safety and tolerability profile of edaravone oral suspension."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Pulmonary Disease

Efficacy and Safety of Once Daily Dosing vs. Approved On/Off Dosing of Edaravone Oral Suspension Up to 48 Weeks in Patients With Amyotrophic Lateral Sclerosis (Study MT-1186-A02). (PubMed, Muscle Nerve) - P3 | "Daily edaravone oral suspension did not show superiority and had equivalent safety and tolerability vs. the approved On/Off regimen, reinforcing the appropriateness of the approved dosing regimen."

Clinical • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Describing the Amyotrophic Lateral Sclerosis US Population and Use of Supportive Aids and Interventions: Results from a Real-World Survey (ISPOR 2025) - "Of these, 63% were prescribed riluzole, 23% oral edaravone, and 17% IV edaravone... These findings describe the consulting pALS population in the US, highlighting the substantial and varied use of supportive aids/interventions, with a greater number of pALS who consulted in SC using expensive mobility and communication aids."

Clinical • Real-world • Real-world evidence • Amyotrophic Lateral Sclerosis • CNS Disorders • Infectious Disease

Biomarkers for Postoperative Intimal Hyperplasia. (PubMed, Int J Angiol) - "In Group edaravone, free-radical scavenger, edaravone (Radicut ® , Mitsubishi Tanabe Pharma Corp., Osaka Japan) was administered, instead of saline...The serum IL-8 levels in Group edaravone were appeared to be suppressed but not significant (132 ± 24 pg/mL, p  = 0.72). It is very important to detect the biomarker such as the serum IL-8, before the establishment of postoperative intimal hyperplasia."

Biomarker • Journal • CXCL8

Mitsubishi Tanabe Pharma America Announces Publication of Preclinical Research on the Role of Edaravone in Mitigating TDP-43 Mislocalization in ALS (PRNewswire) - "Mitsubishi Tanabe Pharma...announced the publication of new preclinical research in Free Radical Biology and Medicine, highlighting the role of edaravone in mitigating TDP-43 mislocalization, a hallmark feature observed in more than 97% of sporadic amyotrophic lateral sclerosis (ALS) cases...In ALS patient-derived neurons from a patient with ALS harboring a TDP-43 mutation, edaravone significantly reduced the cytoplasmic accumulation of TDP-43, restoring its nuclear localization; Unlike vitamin C, edaravone preserved neurite structures and reduced neurotoxicity, supporting a unique mechanism of action; Edaravone treatment induced significant changes in gene expression as early as six hours post-treatment, with key pathways related to protein degradation and neuroprotection; Edaravone's effects were associated with modulation of the SIRT1-XBP1 pathway, a key regulator of cellular stress responses, suggesting a broader role in ALS neuroprotection."

Preclinical • Amyotrophic Lateral Sclerosis

Long-term Function and Survival of Radicava ORS® (Oral Edaravone)-Treated Patients With ALS vs Propensity Score–Matched PRO-ACT Historical Controls (AAN 2025) - "Analysis of MTPA oral edaravone–treated patients with ALS from MT-1186 studies suggests MTPA oral edaravone significantly increases survival and decreases functional decline vs PRO-ACT placebo."

Clinical