Efficacy of Radicava® IV (intravenous edaravone) in subjects with differing trajectories of disease progression in amyotrophic lateral sclerosis: Use of a novel statistical approach for post hoc analysis of a pivotal phase 3 clinical trial.

Introduction: Subjects with amyotrophic lateral sclerosis (ALS) treated with Radicava® (edaravone) IV (intravenous; Mitsubishi Tanabe Pharma America [MTPA], hereafter "MTPA IV edaravone") in Study MCI186-19 had a significantly slower physical functional decline vs placebo-treated subjects as measured by the revised ALS Functional Rating Scale (ALSFRS-R) and analyzed by the linear mixed model for repeated measures (MMRM). This Study 19 post hoc analysis of MTPA IV edaravone-treated and placebo-treated subjects evaluated linear and nonlinear latent class mixed models defining trajectories based on identifying the model with the lowest Bayesian information criterion. The best model differentiated 4 nonlinear trajectories in ALS subjects.

The effects of intervention with intravenous edaravone in Study 19 on hospitalization, tracheostomy, ventilation, and death in patients with amyotrophic lateral sclerosis.

Introduction/aims: Intravenous (IV) edaravone is a US Food and Drug Administration-approved treatment for amyotrophic lateral sclerosis (ALS), shown in clinical trials to slow physical functional decline. In this study we compared the effect of IV edaravone (edaravone-first group) versus placebo followed by IV edaravone (placebo-first group) on survival and additional milestone events.

Methods: This work is a post hoc analysis of Study 19/MCI186-19, which was a randomized, placebo-controlled, phase 3 study investigating IV edaravone versus placebo.

Design and performance characterization of a new LISA-like (laser interferometer space antenna-like) gravitational reference sensor and torsion pendulum testbed.

In this paper, we present the design and performance of the upgraded University of Florida torsion pendulum facility for testing inertial sensor technology related to space-based gravitational wave observatories and geodesy missions. In particular, much work has been conducted on inertial sensor technology related to the Laser Interferometer Space Antenna (LISA) space gravitational wave observatory mission. A significant upgrade to the facility was the incorporation of a newly designed and fabricated LISA-like gravitational reference sensor (GRS) based on the LISA Pathfinder GRS.

Oral edaravone demonstrated a favorable safety profile in patients with amyotrophic lateral sclerosis after 48 weeks of treatment.

Introduction/aims: An intravenous (IV) formulation of edaravone has been shown to slow the rate of physical functional decline in amyotrophic lateral sclerosis (ALS). An oral suspension formulation of edaravone was recently approved by the United States Food and Drug Administration for use in patients with ALS. This study assessed the safety and tolerability of oral edaravone.

Pharmacokinetics, Bioavailability, and Swallowing Safety With Riluzole Oral Film.

Dysphagia is highly prevalent in patients with amyotrophic lateral sclerosis (ALS). Riluzole is a US Food and Drug Administration-approved treatment for ALS. Riluzole oral film (ROF; Exservan™) contains riluzole in a polymer-based film matrix.

Analysis of the US Safety Data for Edaravone (Radicava) From the Third Year After Launch.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease with no curative therapies. Edaravone (Radicava) (Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan), approved in the United States (US) for ALS in adults in 2017, was shown in a clinical trial to slow the rate of physical functional decline in ALS and is administered intravenously. The aim of this paper is to summarize the observed safety profile from real-world patient use during the first 3 years of edaravone availability in the US.

Edaravone efficacy in amyotrophic lateral sclerosis with reduced forced vital capacity: Post-hoc analysis of Study 19 (MCI186-19) [clinical trial NCT01492686].

Background: Edaravone slowed the rate of functional decline in subjects with amyotrophic lateral sclerosis (ALS) in phase 3 study MCI186-19 (Study 19). One of the Study 19 inclusion criteria was forced vital capacity (FVC) ≥80% of predicted (≥80%p). Therefore, the study provided no information on edaravone efficacy in subjects with FVC <80%p.

Slowing the loss of physical function in amyotrophic lateral sclerosis with edaravone: Post hoc analysis of ALSFRS-R item scores in pivotal study MCI186-19.

Introduction: Phase 3 study MCI186-19 demonstrated less loss of physical function with edaravone versus placebo, as measured by the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score. A 1-point drop in an individual ALSFRS-R item may be clinically meaningful. We assessed ALSFRS-R item score changes to identify clinical features protected by edaravone treatment.

Radicava/Edaravone Findings in Biomarkers From Amyotrophic Lateral Sclerosis (REFINE-ALS): Protocol and Study Design.

Objectives: To identify putative biomarkers that may serve as quantifiable, biological, nonclinical measures of the pharmacodynamic effect of edaravone in amyotrophic lateral sclerosis (ALS) and to report real-world treatment outcomes.

Methods: This is a prospective, observational, longitudinal, multicenter (up to 40 sites) US study (Clinicaltrials.gov; NCT04259255) with at least 200 patients with ALS who will receive edaravone for 24 weeks (6 cycles; Food and Drug Administration-approved regimen).

Evidence for generalizability of edaravone efficacy using a novel machine learning risk-based subgroup analysis tool.

The edaravone development program for amyotrophic lateral sclerosis (ALS) included trials MCI186-16 (Study 16) and MCI186-19 (Study 19). A cohort enrichment strategy was based on a Study 16 post hoc analysis and applied to Study 19 to elucidate a treatment effect in that study. To determine whether the Study 19 results could be generalized to a broader ALS population, we used a machine learning (ML) model to create a novel risk-based subgroup analysis tool.

Current and Future Projections of Amyotrophic Lateral Sclerosis in the United States Using Administrative Claims Data.

Background: Various methodologies have been reported to assess the real-world epidemiology of amyotrophic lateral sclerosis (ALS) in the United States. The aim of this study was to estimate the prevalence, incidence, and geographical distribution of ALS using administrative claims data and to model future trends in ALS epidemiology.

Methods: We performed a retrospective analysis of deidentified administrative claims data for >100 million patients, using 2 separate databases (IBM MarketScan Research Databases and Symphony Health Integrated DataVerse [IDV]), to identify patients with ALS.

Clinical staging in amyotrophic lateral sclerosis: analysis of Edaravone Study 19.

Objective: This was a post hoc analysis of the Edaravone Phase III Study MCI186-19 ('Study 19') to examine the utility of clinical staging systems as end points in clinical trials in amyotrophic lateral sclerosis (ALS).

Methods: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised item scores from Study 19 were retrospectively mapped to King's stage and Milano-Torino staging (MiToS) stage. We assessed the percentage of patients who experienced progression in King's and MiToS stages during Study 19.

Engaging ALS patients and caregivers (the ALS research ambassadors) to help design the REFINE-ALS biomarker study.

In the planning and design of the adicava/daravone indings Biomarkrs From myotrophic ateral clerosis (REFINE-ALS) study, we sought to elicit feedback from patients with ALS and their caregivers to ensure that patient-centric issues would be addressed. Ten ALS Clinical Research Learning Institute (ALS-CRLI) Research Ambassadors participated in 2 meetings. They provided perspectives on patients' interest in the study, the schedule of study visits, and data sharing.

Long-term edaravone efficacy in amyotrophic lateral sclerosis: Post-hoc analyses of Study 19 (MCI186-19).

Background: In a Phase 3 study, amyotrophic lateral sclerosis (ALS) patients experienced significantly less physical functional decline with 24-week edaravone vs placebo, followed by open-label treatment for an additional 24 weeks.

Methods: Outcome (the change in ALS Functional Rating Scale-Revised, ALSFRS-R, from baseline) was projected for placebo patients through 48 weeks and compared with 48-week edaravone or 24-week edaravone after switching from placebo.

Results: A total of 123 patients received open-label treatment (65 edaravone-edaravone; 58 placebo-edaravone).

analyses of the edaravone clinical trials Study 16 and Study 19: a step toward more efficient clinical trial designs in amyotrophic lateral sclerosis.

The edaravone development program established a study design in which a treatment effect slowing functional loss in amyotrophic lateral sclerosis (ALS) could be documented within a 24-week time frame. This report elucidates the strategic enrichment design utilized to create efficiency and precision in the development program. analyses describe learning, sequential iteration, and evolution in study design.

A new torsion pendulum for gravitational reference sensor technology development.

We report on the design and sensitivity of a new torsion pendulum for measuring the performance of ultra-precise inertial sensors and for the development of associated technologies for space-based gravitational wave observatories and geodesy missions. The apparatus comprises a 1 m-long, 50 μm-diameter tungsten fiber that supports an inertial member inside a vacuum system. The inertial member is an aluminum crossbar with four hollow cubic test masses at each end.