On May 5, 2017, the FDA and the company made their announcements: Radicava (edaravone) was approved for the treatment of ALS in the United States. Mitsubishi Tanabe Pharma America, Inc., told the ALS community that they would have the drug accessible to physicians to write prescriptions just a few months later. This feat would require a large number of obstacles to be overcome as the company had never brought a drug to market in the USA before. However, they met the challenge and Radicava became available August, 8, 2017 and people with ALS across the U.S. started making the antioxidant part of their overall ALS treatment routine.

Will people with ALS take it?

“When I heard there was a drug being approved that had the potential to slow the progression of ALS, I was overjoyed. With the FDA pushing it through, it gave me and my family a lot of hope that we would have longer time together as a family, with a sense of normalcy.

I think the glimmer of hope for more time, to delay the progression so that more and more drugs could be found is a huge part of day-to-day living for us that creates a positive attitude. I really believe that positivity has helped my own progression to be slower than we would have thought early on in the disease.”

- Joseph Gregory, person with ALS, Washington DC Metro Area.

Since it became available, more than 2,500 people with ALS have accessed Radicava, according to the company. The treatment is delivered via intravenous infusion basically two weeks on and two weeks off. Edaravone aims to address something called oxidative stress occurring in the cells, which is thought to be caused by an overabundance of certain molecules of oxygen called “free radicals”. Once infused into a person’s blood stream edaravone diffuses around their body finding those molecules and helping the body to then dispose of them. Hence this class of drugs are often referred to as free radical scavengers.

Since edaravone is infused intravenously, it is common for a person with ALS to have a permanent port or line placed in their body so that they don’t have a new i.v. placed each day. This procedure is quite standard; however, it does leave a person with some additional maintenance required, especially during the drug holiday periods. Most people will have their first edaravone treatment done in a clinic setting, or at an infusion center, of which hundreds have signed up to offer the treatment in their facilities.

One of the most surprising things that has occurred is that more people with ALS taking Radicava have been able to manage the infusion process at home. According to the company, 50% of those that have accessed Radicava have moved to at-home infusions. By most accounts, being able to infuse at home provides people with ALS greater comfort and flexibility in staying on schedule with the two-week cycles rather than having the treatment provided at an infusion center or ALS clinic.

Use Remains Mixed Across Clinics

Access and use of the newly approved treatment varies between ALS clinics, with some reportingly having hundreds of patients on the drug early on in its availability while others reported having no patients taking edaravone.

Some people in the ALS community speculate this difference between usage among ALS clinics is due in part because neurologists from the U.S. weren’t involved in any of the original clinical research studies of edaravone. All the original clinical trials of edaravone were conducted in Japan. This lack of exposure created unfamiliarity with the drug and its potential impacts on disease progression among prescribers.

Another viewpoint as to why usage hasn’t been higher may be that physicians are considering a patient’s overall quality of life. Yeo & Simmons argue in Discussing edaravone with the ALS patient: an ethical framework from a U.S. perspective (2017) that a physician ought to take the time to understand the “modest impact” from treatment seen in trials rather than simply read the excitement from advocacy groups. Their framework suggests physicians take a more comprehensive look at the quality of life of a patient, including assessing and discussing with them the risks, costs, challenges and impact of treatment on quality of life, when discussing Radicava as a treatment option.

Mixed Coverage Among American Health Insurers

Another reason why people with ALS aren’t accessing Radicava in even larger numbers has to do with big differences in coverage from health insurers. The list price of edaravone for a single year of treatment is approximately $148,000. While few people with ALS will actually pay that price, the portion of it that they are on the hook for differs greatly depending on the prescription coverage plan their insurer developed for edaravone.

Medicare and the Veterans Administration offers coverage to their subscribers as per the FDA label: to all those with an ALS diagnosis. Generally speaking, these programs pick up at least 80% of the cost of the drug [i]. The drug maker does offer further cost assistance programs, but those programs are not available to individuals on public insurance programs.

When it comes to private insurance programs, it gets a more complicated. While edaravone has been studied in people with ALS in Japan for more than a decade, across many different clinical trials, most of those trials failed to show any benefit from treatment in people with ALS. However, through post hoc analysis of data from those trials, researchers identified what they felt was a set of characteristics for a person with ALS which predicted whether or not they would show benefit. These were the used as criteria for enrollment in the pivotal phase 3 study done in Japan:

functionally retained most activities of daily living (defined as 2 pts or more on each of the individual questions on the ALSFRS-R scale

a normal respiratory function defined as having 80% of more via FVC measures

a diagnosis meeting the El Escorial Criteria for probable or definite ALS

Disease duration of 2 years or less

(It’s important to note that 90% of people in the study were taking a stable dose of riluzole at the time they started in trial as well.)

A slowing of disease progression was found to be statistically significant at the six-month mark in the treatment group when enrollment as limited to the above characteristics [ii]. However, the FDA approved marketing to all those with ALS, including those outside these characteristics.

Private insurers have significant flexibility under the law to determine which drugs they will cover and to whom they will offer coverage. Some private insurers have developed guidance limiting coverage to only their subscribers with ALS whom met this criterion at the time they start edaravone treatment (example, United Healthcare). Some insurers also required that a person with ALS who is offered coverage show they continue to meet criteria, such as high FVC measures, after six months in order to continue to receive coverage (example, Tufts Healthcare), while still others require that a person actually show benefit from treatment after six months (example, Aetna Healthcare).

As a result of this, many people with ALS are being denied coverage by their health insurers. At least initially, as many people with ALS have reported being able to access coverage by following the appeal procedures with their insurer. Still, others take no for an answer and pursue other potential treatment options.

Treatment as Impact

Since people started being able to get edaravone in the US, patients, physicians and researchers alike have been closely watching for disease progression changes that can be associated with the treatment.

With nearly 10% of the population of people in the U.S. living with ALS now having accessed Radicava over the last year, large efforts have begun to get underway to understand its impact on disease progression. Research regarding usage and impact of edaravone in people with ALS is likely to be discussed at conferences and published in journals for many years.

Other efforts are underway to provide people with ALS more immediate access to information regarding the impact edaravone may be having on their own individual journey with ALS. Through programs like the Precision Medicine Program, people with ALS use at home tools to monitor their disease progression, which can empower them with more immediate knowledge regarding the potential impact any FDA approved treatment for ALS, such as edaravone, or experimental medications they are trial in trials, among other interventions used along the way, may be having on their disease progression.

The Precision Medicine Program started by the ALS Therapy Development Institute offers people with ALS tools to monitor their disease progression, including the same gold standard scale (ALSFRS-R) that is used in the clinic. Those who enroll in the PMP are invited to wear accelerometers which measure their movements on all four limbs on a monthly basis, for as long as they are able to do so. Data from both of these measures are plotted on graphs which are accessible to the patient through a secure portal at home. Voice recordings are collected too, among those that are able to do them. Other experiments on the human genome, microbiome, and induced pluripotent stem cell-based modelling and drug screening efforts are part of the overall PMP program.

"Being able to independently keep track of my physical movements by wearing accelerometers, recording my voice, and answering ALSFRS-R questions every month keeps me incredibly informed on how I am progressing. In a disease with very little answers when it comes to various rates of progression, I'd be lost and overwhelmed if I didn't have access to the advanced analytics and real-time data that the PMP provides me.

By having a baseline of data before taking Edaravone, I had a very accurate measure of how I was progressing on a monthly basis. After a few cycles of edaravone and staying on top of my monthly PMP tasks, I had access to data that informed me of the actual effectiveness that edaravone was having on me. Therefore, I am able to compare the baseline data of my progression before starting Edaravone with the data compiled when I was actually taking the drug."

- Osiel Mendoza, person with ALS, San Francisco Bay Area

Early analysis comparing voice and accelerometer data conducted by internal scientists as ALS TDI as well as together with experts at Google suggest that these at-home monitoring approaches may be predictive in a more sensitive way than ALSFRS-R, which could lead to faster trials for all down the road.

Most immediately, dozens of people taking edaravone have enrolled in the PMP and are using these tools to track their disease progression and in partnership with their medical teams determine impact the treatment may be having overtime. Prescreening for PMP enrollment can be completed online. More than 500 of the 750 spots available in the program are already filled.

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The FDA approved edaravone to be marketed as a treatment for ALS on May 5, 2017 and since then significant steps have been taken in making edaravone treatment part of the standard of care in practice for people with ALS.

Over the last year, 2,500 people with ALS have at least accessed the treatment. However, it is not known how many of them stayed on treatment for 6 months or longer or what percentage of them starting taking the medication at the same time those in the trial that saw benefit did. Other people with ALS have experienced difficulty getting the FDA approved medication due to differences in coverage across private insurers, as well as the high cost of the medication still faced by those covered under Medicare.

Most trials that started after prescriptions for edaravone started to be filled in the US are allowing patients to stay on the drug if they choose to enroll. This last year has seen a lot happen and the momentum for the discovery of additional treatments for ALS has never been stronger.

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[i] Actual cost to patient will vary greatly even among those on public insurance.

[ii] A study followed those enrolled in this study for an additional six months saw similar outcomes continue beyond the six-month mark. While that study result was not included in the FDA review it was published several months following FDA approval.