Radicava, also known by its generic name edaravone, is the first treatment approved by U.S. Food and Drug Administration (FDA) in more than two decades to help amyotrophic lateral sclerosis (ALS) patients. While awaiting its arrival, ALS News Today spoke to the company responsible for its U.S. launch, Mitsubishi Tanabe Pharma America, about the therapy’s approval, cost, and what can be expected in terms of access.
Edaravone, originally developed MT Pharma’s parent company — Mitsubishi Tanabe Pharma Corporation — was approved in 2001 by regulatory officials Japan to treat brain damage caused by stroke. Known as Radicut in Japan, the drug’s ability to protect neurons from damage caused by the accumulation of oxygen reactive elements — and the inflammation they consequently cause — led researchers to wonder about its potential in treating neurological conditions like ALS.
“The journey started — as modern medical breakthroughs sometimes do — when one inquisitive neurologist who saw its impact in another neurological condition asked, ‘could edaravone have impact in ALS?’” Dr. Jean Hubble, vice president for Medical Affairs at MT Pharma America, said in the interview, conducted by email.
After 13 years of clinical development that spanned three Phase 3 studies conducted in Japan — designated MCI186-16 (NCT00330681), MCI186-17 (NCT00424463), and MCI186-19 (NCT01492686) — the clinical efficacy of edaravone as an ALS treatment was evident.
“Slowing the decline of that loss of function in ALS is incredibly important,” Hubble said. “Depending on people’s level of function when they begin treatment, the impact edaravone demonstrated in clinical trials could translate into potentially helping people preserve function longer, assisting their ability to get out of bed, feed themselves, or even hug their loved ones.”
Radicava and clinical tests
The MCI186-16 study started in 2006, randomly assigning 206 ALS patients to receive either edaravone or placebo for 14 days followed by 14 days without therapy, or for 28-day treatment cycles. This 24-week study found that edaravone led to a reduction of functional loss in treated patients compared to placebo. Although the benefits seen were not significant, they justified further examination in MCI186-17, a 36-week extension of the earlier trial.
Importantly, analyses of trial results pointed to particular benefit in a specific subgroup of patients — those with earlier onset ALS and lesser disability — and this subset “set the path for future clinical trials,” according to an MT Pharma timeline of Radicava’s development. The treatment, however, is approved for use by all ALS patients.
“We know people with ALS never give up and neither did we. Each clinical trial became an opportunity to learn more about ALS and how edaravone could benefit patients,” Hubble said, when asked about the turn in focus toward this subset of patients.
In what would become a pivotal Phase 3 trial for edaravone, MCI186-19, researches tested its efficacy in ALS patients who began experiencing symptoms within two years of the study’s start and who were relatively independent in their ability to perform basic tasks, like eating and walking unassisted. Specifically, according to a study published in the journal Neurology in 2015, the 137 ALS patients in this final study all had:
- definite or probable ALS diagnostic, in accordance with the EL Escorial and Airlie House diagnostic criteria
- Japan ALS severity classification grade inferior to 3
- confirmed ALS Functional Rating Scale-Revised (ALSFRS-R) score above 2 points
- confirmed forced vital capacity (%FVC) above 80%
- ALS symptoms onset prior to treatment of 2 years maximum
In 2014, final trial results confirmed the clinical efficacy of edaravone, with those given long-term treatment, for 7 to 15 months, indeed showing a lesser decline in motor functions compared to placebo.
Treated patients experienced a clinically meaningful reduction of 33 percent in the rate of decline of physical function. During a 48-week extension study, these patients also continued to show a statistically significant reduction in disease progression.
“In addition, patients initially given Radicava had approximately 58 percent relative risk reduction in death or certain disease progression events (e.g., loss of upper limb function) compared to those initially given placebo,” Hubble said.
In all these clinical trials, edaravone was shown to be safe and well-tolerated, with no significant differences in adverse events between groups other than more bruising in those given edaravone. Walking problems were also noted as a common side effect.
Supported by these positive results, Radicut was approved to treat ALS in Japan and South Korea in 2015. This led the FDA to contact MT Pharma America, and encourage the company to move toward a marketing application in the United States. Unusually, the agency did not require that the Japanese trials be repeated in an American patient population.
“Given the urgency of the need in ALS, the FDA did not require us to repeat time-consuming clinical trials in the U.S., which would have added several years to the timeline,” Hubble said. “Instead, we relied on the comprehensive clinical trial program and MCI186-19, which formed the basis of our NDA [New Drug Application].”
The FDA accepted the NDA filing in August 2016, and approved the treatment, under the brand name Radicava, on May 5, 2017 — bringing a first new ALS treatment onto the U.S. market since riluzole was approved in 1995.
Whether European approval is also being sought is still an open question. Debbie Etchison, director for Public Affairs & Corporate Communications at MT Pharma America, declined to address that point directly in the interview, saying instead, “At the moment, our focus is getting Radicava to patients in the U.S. as quickly as possible.”
Cost and other questions
Radicava is administrated intravenously, with an initial treatment cycle of daily infusions for 14 consecutive days, followed by a two-week drug-free period. The treatment is then administrated for 10 of the next 14 days, followed again by two-week drug-free period. Each infusion lasts for about 60 minutes, during which patients receive 60 mg of the drug.
Whether the treatment will be administrated at an infusion center or a patient’s home is likely be determined by an individual’s doctor and insurance coverage. MT Pharma is planning to ship Radicava to both “ALS Centers, and to specialty pharmacies that can deliver it to patients who will receive treatments in their homes,” Etchison said.
Radicava’s list price is $1,100 per infusion and $145,000 per year — a price that is “the mid-point for an orphan drug in the U.S. and represents the investment MT Pharma is making to deliver it to U.S. patients,” Etchison said. Two factors were key, she added: the development and business investments necessary for FDA approval, and the costs of establishing the “business infrastructure” for marketing a first product in the U.S.
The list price, she also noted, is likely not the price patients will pay for Radicava. MT Pharma has also set up an assistance program, called Searchlight Support, that links ALS patients with a case manager to help with Radicava access, insurance coverage, and related issues.
The program will provide Radicava to eligible patients at no charge, for up to two months, while insurance coverage is determined. “Commercially-insured ALS patients will pay minimal out-of-pocket costs for RADICAVA through a MTPA co-pay support program,” Etchison added.
MT Pharma America will continue to study Radicava to further understand its potential to help those with ALS.
“We believe Radicava offers new hope for people with ALS and exemplifies MT Pharma America’s commitment to innovative therapies for patients in the United States battling life-threatening diseases,” Hubble said.