FDA Approves Radicava, First New ALS Therapy in 22 Years

The first treatment for amyotrophic lateral sclerosis (ALS) in more than two decades, Radicava (edaravone), has been approved by the  U.S. Food and Drug Administration and will soon be available to patients.

The May 5 FDA decision, hailed by physicians and ALS advocates, brings hope to the ALS community that treatment development, after a long slumber, is again on the move.

“We hope today’s announcement signals the beginning of a new chapter in the fight against this terrible disease,” Barbara Newhouse, president and CEO of the ALS Association, said in a press release.

The approval is based on data from a Phase 3 clinical trial (NCT01492686) in Japan, which demonstrated Radicava’s ability to slow decline in the daily functioning of ALS patients. The trial led to the treatment’s approval in Japan and South Korea in 2015 — an act that caught the FDA’s attention, bringing the agency to contact with the drug developer’s American subsidiary,  Mitsubishi Tanabe Pharma America (referred to simply as MT Pharma).

“After learning about the use of edaravone to treat ALS in Japan, we rapidly engaged with the drug developer about filing a marketing application in the United States,” Eric Bastings, MD, deputy director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in an FDA press release.

“This is the first new treatment approved by the FDA for ALS in many years, and we are pleased that people with ALS will now have an additional option,” Bastings said.

Similar reactions were heard from neurologists and patient advocates, cited in an MT Pharma press release.

“For people with ALS and their families, having a new therapy which slows the decline of physical ability is incredibly significant,” said Jonathan S. Katz, MD, ALS clinic director of the Forbes Norris MDA/ALS Research and Treatment Center at California Pacific Medical Center. “This is an uplifting milestone for the ALS community especially since it’s been so long since we had anything new.”

“This is an important time for people living with ALS,” Newhouse added.

According to the ALS Association, the treatment’s list price is $1,000 per infusion, or about $146,000 annually, and it is expected to be available for use by August.

Clinical trial results

Results from the six-month Japanese clinical trial — in which 137 patients were randomized to receive either Radicava or placebo — showed that Radicava reduced the decline in physical ability by 33 percent compared to placebo, the company said.

Researchers measured physical function using the ALS Functional Rating Scale-Revised (ALSFRS-R). The difference in decline seen between the groups equaled 2.49 ALSFRS-R points.

“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,” said Atsushi Fujimoto, president of MT Pharma America.

“The approval of Radicava brings us into a new era of treatment by evolving how we manage this complex disease,” added Katz.

How Radicava works

Radicava helps to control excessive oxidative stress in the body. Research shows that in ALS, damaging oxidative processes occur at a higher than normal rate.

The drug is given by intravenous infusion, in a relatively intense schedule of 28-day cycles. Treatment starts with daily infusions for 14 days, followed by 14 days of rest. During later treatment cycles, patients receive Radicava for 10 of 14 days, again followed by a 14-day treatment-free period. Each infusion lasts for about 60 minutes, during which patients receive 60 mg of the drug.

The most common side effects — seen in more than 10 percent of patients — were bruising, gait problems, and headache.

But both the FDA and MT Pharma underscore that although Radicava was seen to help many patients, its use can also cause serious — even life-threatening — side effects. Particularly, severe allergic reactions, known as an anaphylactic shock, can occur both during and after an infusion.

Radicava contains sodium bisulfite, and in addition to general allergic reactions to Radicava, some patients are allergic to the compound. Sulfite allergy can make itself known as both mild reactions and a life-threatening anaphylactic shock. People with asthma are particularly prone to a sulfite allergy.

If patients experience hives; swelling of the lips, tongue, or face; fainting; breathing problems; wheezing; trouble swallowing; dizziness; itching; or an asthma attack (in asthmatics), they should immediately contact their doctor or seek emergency care.

Since these reactions occurred in people once the drug was approved and were reported spontaneously, MT Pharma cannot provide numbers of how common such reactions are.

Patient support programs

MT Pharma has launched a support program for patients prescribed Radicava to help them with its $1,000 per infusion list price. The Searchlight Support assigns a personal case manager to each patient, who assists in ensuring coverage by health insurance providers.

Case managers also help with other aspects of access, including transportation to infusion clinics, navigating co-pay support programs, and patient assistance programs for the uninsured. Support can be reached through the company’s website or by phone at 1-844-SRCHLGT (772-4548)

“We recognize how important this therapy may be to people with ALS and are committed to helping provide access to this important treatment option, with the goal of keeping out-of-pocket costs at a minimum for eligible patients,” said Atsushi Fujimoto, president of MT Pharma.

Radicava’s way to the U.S.

MT Pharma underscored that Radicava has gone through several Phase 3 trials, with a total time in clinical development of 13 years. No studies were performed at U.S. institutions.

However, the company presented trial data at scientific conferences in North America, including the American Academy of Neurology (AAN) Annual Meeting in Canada in 2016, and further updates at the AAN 2017 Annual Meeting in Boston in April.

The drug was originally developed by Japanese Mitsubishi Tanabe Pharma Corporation, and the clinical program there led to its approval in Japan and South Korea in 2015. In that same year, Radicava was granted orphan drug designation by the FDA, following the decision of its EU counterpart, the European Medicines Agency.

The company filed a New Drug Application (NDA) in June with the FDA, which accepted it for review on Aug. 30. Radicava’s approval on May 5 came more than a month before the FDA’s announced action date, which was set for June 16, 2017.

“We applaud the work MT Pharma America and the FDA are doing as they have taken unprecedented steps to get this treatment into the hands of patients as quickly as possible,” said Newhouse, who is familiar with the Japanese company.

MT Pharma became the ALS Association’s national corporate sponsor of the Walk to Defeat ALS, a nationwide campaign aiming to support care service programs, research, and advocacy efforts, in 2016.

To Newhouse, FDA approval signifies much more than a long-overdue new therapy option — it brings renewed hope that treatment development is again on the move.

“The approval of Radicava gives great promise for what we hope will be the first of many new treatments,”  she said in the MT Pharma release. “There are several drugs to treat ALS currently in clinical trials and we are hopeful that people living with ALS have even more therapies available to them sooner rather than later.”

The only other treatment specifically indicated for ALS, the oral tablet riluzole (Rilutek), was approved by the FDA in 1995.