To compare the effect of riluzole on median survival in population studies of patients with amyotrophic lateral sclerosis (ALS) with that observed in clinical trials. Methods: Two independent PubMe...

We aimed to evaluate overall survival in US patients with amyotrophic lateral sclerosis (ALS) treated with intravenous (IV) edaravone compared with those not treated with IV edaravone in a real-world setting. This exploratory retrospective comparative effectiveness observational analysis included patients with ALS who were enrolled in an administrative claims database from 8 August 2017 to 31 March 2020. Propensity score matching identified IV edaravone-treated patients (cases) and non-edaravone-treated patients (controls) matched for covariates: age, race, geographic region, sex, pre-index disease duration, insurance, history of cardiovascular disease, riluzole prescription, gastrostomy tube placement, artificial nutrition, noninvasive ventilation, and all-cause hospitalisation. For cases, the index date was the date of the first claim for IV edaravone. For controls, it was the date IV edaravone was available (8 August 2017). The effect of IV edaravone on all-cause mortality was estimated with shared frailty Cox regression analysis. 318 cases were matched to 318 controls. In both groups, 208 patients (65.4%) had a history of riluzole prescription. As of 31 March 2021, there were 155 deaths (48.7%) among the cases and 196 among the controls (61.6%). Median overall survival time was 29.5 months with edaravone and 23.5 months without, respectively, and the risk of death was 27% lower in cases than in controls (HR, 0.73; 95% CI, 0.59–0.91; p=0.005). In this real-world analysis, IV edaravone treatment in a large predominantly riluzole-treated US cohort was associated with prolonged overall survival compared with not using IV edaravone. Data from adequately powered RCTs are needed to support this finding. Funded by Mitsubishi Tanabe Pharma America.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with motor neuron loss as a defining feature. Despite significant effort, therapeutic breakthroughs have been modest. MN-166 (ibud... Lay abstract Amyotrophic lateral sclerosis (ALS) is a neurological disease defined by the loss of the nerve cells going to the muscles. Despite significant effort, we still do not have good treatme... Tweetable abstract MN-166 (ibudilast) is a promising neuroprotective agent for the treatment of neurodegenerative disease. The clinical trial protocol in #fsgnmt provides a summary of the ongoing #...

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. In Study 19, 24-week, double-blind treatment was followed by open-label treatment where all subjects received edaravone. At 24 weeks, some subjects had FVC <80%p (FVC₂₄ <80%p). This allowed for post-hoc assessment of the effects of edaravone in subgroups of subjects with FVC₂₄ ≥80%p vs <80%p. Objective: To address the question of the efficacy of edaravone in ALS patients with FVC <80%p. Methods: Post-hoc analysis of Study 19 comparing edaravone efficacy at week 48 in subjects with FVC₂₄ ≥80%p vs <80%p. Results: With edaravone treatment, subjects in both the FVC₂₄ ≥80%p and the FVC₂₄ <80%p subgroups experienced a reduction in ALS Functional Rating Scale-Revised (ALSFRS-R) score loss vs placebo subjects through week 48. For the FVC₂₄ ≥80%p subgroup, the changes in ALSFRS-R scores from baseline to week 48 were −7.63 for edaravone-edaravone vs −9.69 for placebo-edaravone, a difference of 2.05 (P = .034; 95% CI: 0.16, 3.94). For the FVC₂₄ <80%p subgroup, the changes in ALSFRS-R scores from baseline to week 48 were −10.26 for edaravone-edaravone vs −15.20 for placebo-edaravone, a difference of 4.94 (P = .0038; 95% CI: 1.64, 8.25). Linear regression analysis indicated that, in the FVC₂₄ <80%p subgroup, there was a notable change in the slope of the ALSFRS-R score-vs-time graph after the start of edaravone treatment. Conclusion: ALS subjects in the Study 19 placebo arm had a slowing in disease progression, even when edaravone was added with an FVC of <80%p prior to starting edaravone. A randomized, placebo-controlled study is needed to validate these post-hoc findings.

During amyotrophic lateral sclerosis progression, up to 85% of patients develop dysphagia. Riluzole oral suspension 50 mg/10 mL is bioequivalent to riluzole 50-mg film-coated tablets administered orally under fasting conditions. Here, we compare the bioavailability of a single 50-mg dose of riluzole oral suspension via intragastric tube, a proxy for percutaneous endoscopic gastrostomy administration, with that of oral administration in healthy volunteers under fasting conditions. Secondary objectives included the plasma pharmacokinetic and safety profiles of each administration route. This was a single-center, single-dose, open-label, randomized, 2-period, 2-sequence, crossover bioequivalence/bioavailability study. Healthy volunteers were randomized to riluzole oral suspension 50 mg/10 mL either via nasogastric tube or orally, with a 5-day washout before crossover. A total of 32 subjects were randomized (safety population); 30 were eligible for pharmacokinetic analysis. The ratios (nasogastric tube/oral) of the geometric least squares means and the geometric 90% CIs of AUC_0-t, AUC_0-inf, and C_max were calculated to be 90.60% (85.66%-95.82%), 90.43% (85.47%-95.67%), and 96.99% (89.40%-105.23%), respectively, indicating bioequivalence. No significant differences in C_max, T_max, K_el, and t_1/2el between treatments were found. Overall, riluzole oral suspension was well tolerated. No deaths or other serious adverse events were reported. In this study, riluzole oral suspension was bioequivalent when administered intragastrically and orally in healthy subjects under fasting conditions. Both administration methods were well tolerated. These results show that intragastric administration of riluzole oral suspension may provide an important formulation option in people with amyotrophic lateral sclerosis who have a percutaneous endoscopic gastrostomy tube.