Published in May 2018, the supplement to The American Journal of Managed Care® (available here), entitled “Edaravone in the Treatment of Amyotrophic Lateral Sclerosis: Efficacy and Access to Therapy—A Roundtable Discussion,” reviews the therapeutic spectrum for amyotrophic lateral sclerosis (ALS) and examines the challenges and advancements in study design and research. The expert panel which included Visante CEO Jim Jorgenson also investigates the edaravone clinical development program, discusses interpretation of data from key clinical trials, and explores opportunities for collaboration to increase patient access to treatment.
ALS has been a very difficult and frustrating disease to manage. Despite the remarkable longevity observed in rare patients like Dr. Stephen Hawking, ALS for the majority of patients is a brutally progressive and fatal neuromuscular disease that results in death in 3-5 years from initial onset. The disease is fatal in 50% of patients within 30 months of onset. However, as evidenced by Dr. Hawking,disease course can vary significantly depending on the patient and can be difficult to predict. ALS fortunately is a rare disease affecting approximately 30,000 patients in the US.
Treatment of ALS is difficult. No cure currently exists for ALS and as a result symptom management and palliative care focused on slowing disease progression is the only available approach. Medication therapy choices have been very limited with Riluzole as the only disease-modifying agent approved for ALS treatment. Riluzole has been documented to modestly slow ALS progression. Even though Riluzole was approved in 1995 it has remained the only medication therapy option for ALS until the introduction of edaravone.
Edaravone, developed and studied in Japan by Mitsubishi Tanabe Pharma Corporation for the treatment of ALS, is an antioxidant free-radical scavenger. Based upon the pivotal findings of Mitsubishi’s Study 19, approval for edaravone with the broad indication of treatment of ALS was granted in Japan, South Korea and the US. Although the clinical trials were conducted entirely in Japan, the FDA indicated that the results were generalizable to the US population. Recognizing the unmet need for effective ALS treatment for patients in the US, the FDA granted orphan drug status to edaravone in 2015, and subsequently gave edaravone its approval in 2017 with the broad indication “for the treatment of amyotrophic lateral sclerosis (ALS).” In its review of the edaravone clinical trials, the FDA noted that although there are reasons to believe that edaravone’s efficacy may decrease as ALS progresses to advanced stages, this situation was not a valid reason to limit its use because the “variability of this disease precludes giving accurate information as to where the effect diminishes.”
Edaravone, like many specialty/orphan drugs is expensive and payers naturally want to ensure appropriate patient selection and use. However, a major source of controversy with edaravone has been the approval criteria adopted by many US payers limiting access to the drug to the same subpopulation of ALS patients included in Study 19. The inclusion criteria for Study 19 were intended to be able to demonstrate results using modest sample size and duration. Inclusion criteria for the study were never intended to serve as inclusion criteria for payment or coverage determinations. Typically, the FDA approved indications for a drug serve as the backbone of payer approval decisions with clinical trials serving as additional resources for decisions regarding coverage of “off label” uses. Reversing this approach to limit access to approved FDA indications based on a limited subpopulation would seem to create a situation where payers are “cherry picking” the ways to determine coverage based on the most restrictive approach. This approach is not in the best interests of ALS patients with very limited treatment options and a bleak prognosis. This is certainly an issue to keep an eye on as more experience with edaravone is gained and as more specialty/orphan drugs progress through the approval pipeline.