Safety and Effectiveness of Long-term Intravenous Administration of Edaravone for Treatment of Patients With Amyotrophic Lateral Sclerosis

SPS commentary:

Edaravone is thought to function as a free‐radical scavenger that is hypothesised to protect motor neurones from free‐radical and oxidative‐stress damage. According to an editorial, it was originally developed in the 1980s and marketed in Japan for the treatment of acute ischaemic stroke and repurposed for the treatment of amyotrophic lateral sclerosis (ALS), making it the only the second disease-modifying drug approved for the treatment of ALS in the US, the first since riluzole was approved in 1995. It notes the approval of edaravone by the FDA in 2017 was somewhat of a surprise to many in the ALS scientific and clinical research communities, raising difficult questions about the quality and quantity of the data needed for registration and marketing of new ALS drugs. Edaravone requires continued intravenous injections and costs upwards of $150,000 per year, and never underwent trial in the US, though there were conflicting results from the 2 trials conducted in Japan. It adds that the European Medicines Agency has not approved edaravone and is requiring a larger and longer trial before consideration

It discusses the current study, acknowledging that though the results of an observational trial may be criticised as being less trustworthy than a prospective placebo-controlled trial, its scientific rigor makes it both impressive and believable, with the total number of edaravone-treated patients 3 times the number included in the Japanese trial, and the number of subgroup patients and controls was equal to that in the original positive study. It adds that these data add to the unfortunate experience in ALS clinical trials, in which exciting results in small trials are not reproducible in larger, appropriately powered trials. It suggests that the marketing of drugs that do not generate data that show a consistent and incontrovertible clinical effect (and not just P ≤0 .05) may do more harm than good and unproven drugs for neurodegenerative disease are frequently costly and burdensome for patients and may have toxic effects that outweigh any positive clinical effect. Furthermore, resources may be diverted away from interventions that could actually be more tangibly helpful for patients, and patients may develop false hope based on unrealistic expectations. It concludes that accelerated approval of marginally helpful drugs does not bring closer the long-term goal of developing meaningful treatments to help patients with devastating diseases, whilst the unintended consequences warrant caution for future drug approval decisions.