By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved edaravone, the first new treatment for amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) since the approval of riluzole more than 20 years ago. Edaravone is a potent radical scavenger that received orphan designation and was approved based on a clinical trial conducted in Japanese subjects. It will be marketed as Radicava.
INDICATIONS
Edaravone is indicated for the treatment of ALS.1
DOSAGE
The recommended initial treatment cycle is 60 mg given intravenously over 60 minutes daily for 14 days, followed by a 14-day drug-free period.1 Subsequent cycles are daily dosing for 10 days of a 14-day cycle, followed by a 14-day drug-free period. Edaravone is available as a 30 mg/100 mL single-dose polypropylene bag.
POTENTIAL ADVANTAGES
Edaravone provides a new treatment option for ALS.
POTENTIAL DISADVANTAGES
The most common adverse reactions (vs. placebo) are contusion (15% vs. 9%), gait disturbance (13% vs. 9%), and headache (10% vs. 6%).1 Hypersensitivity reactions, including cases of anaphylaxis, have been reported. The formulation contains sodium bisulfite, which may cause allergic-type reactions in susceptible individuals.1 Edaravone does not appear to be effective in advanced ALS.2 Long-term safety and effectiveness has not been established.
COMMENTS
Edaravone is a radical scavenger initially approved in Japan for treating acute cerebral embolism.2 Its potential neuroprotective effect against oxidative stress in motor neurons led to its evaluation in ALS patients. The efficacy of edaravone was established in a six-month, randomized, placebo-controlled, double-blind study in Japanese subjects.1 Patients were living independently and retained most activities of daily living, normal respiratory function, and had a disease duration of two years or less. Subjects were randomized to edaravone (n = 69) or placebo (n = 68). More than 90% of subjects were treated with riluzole. The primary efficacy endpoint was a comparison of the change between the two treatments in the ALS Functional Rating Scale, Revised (ALSFRS-R) total score from baseline to week 24. ALSFRS-R consists of 12 questions that evaluate fine and gross motor skills, bulbar, and respiratory function of patients, including speech, salivation, swallowing, handwriting, cutting food, dressing/hygiene, turning in bed, walking, climbing stairs dyspnea, orthopnea, and respiratory insufficiency. Each question is scored from 0-4, with a higher score representing higher functionality. At week 24, changes were -5.01 ± 0.64 for edaravone and -7.50 ± 0.66 for placebo (difference, 2.49; 95% confidence interval, 0.99-3.98; P = 0.0013). The treatment effect of edaravone may be limited. An early confirmation study with a larger sample size (n = 206) that included subjects with longer disease duration (≤ 3 years vs. ≤ 2 years) and poorer respiratory function (FVC ≥ 70% vs. ≥ 80%) did not reach statistical significance.2,4
CLINICAL IMPLICATIONS
ALS is a rare, life-threatening, progressive neurodegenerative disease affecting upper and lower motor neurons with a mean survival of three to five years. Edaravone is the latest drug approved for ALS. It appears to show modest benefit in slowing disease decline in patients with short disease duration, good vital capacity, and concomitant use of riluzole. The cost for edaravone is estimated to be $1,303 per injection (60 mg) and is expected to be available in August.5 Edaravone is under evaluation for acute ischemic stroke in several studies.6
REFERENCES
- Radicava Prescribing Information. MT Pharma America. May 2017.
- Sawada H. Clinical efficacy of edaravone for the treatment of amyotrophic lateral sclerosis. Expert Opin Pharmacother 2017;18:735-738.
- Cedarbaum JM, Stambler N, Malta E, et al. The ALSFRS-R: A revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 1999;169:13-21.
- Abe K, Itoyama Y, Sobue G, et al. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener 2014;15:610-617.
- ALS News Today. 9 Things to Know About the New ALS Drug Radicava. Available at: http://bit.ly/2qcLWUM. Accessed June 7, 2017.
- ClinicalTrials.gov. Studies about edaravone. Available at: http://bit.ly/2s44Z9x. Accessed June 7, 2017.
The FDA has approved edaravone, the first new treatment for amyotrophic lateral sclerosis since the approval of riluzole more than 20 years ago.
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