Independent data monitoring committee advises conclusion of study evaluating once-daily dosing of oral edaravone following interim futility analysis
JERSEY CITY, N.J. July 31, 2023 – Mitsubishi Tanabe Pharma America, Inc. (MTPA) today announced the decision to discontinue the global, multi-center, double-blind, Phase 3b MT-1186-A02 study of oral edaravone in amyotrophic lateral sclerosis (ALS), based on results of a pre-planned futility analysis conducted by an independent data monitoring committee (IDMC) composed of external experts. The IDMC’s recommendation to conclude the study was not based on safety or efficacy concerns, and this decision does not impact the commercial availability of the U.S. Food and Drug Administration (FDA)-approved RADICAVA ORS® (edaravone).
Study MT-1186-A02, which was a postmarketing commitment following the FDA approval of intravenous (IV) RADICAVA® (edaravone), was designed to evaluate the superiority of an investigational once-daily dosing regimen of oral edaravone (105 mg) vs. the FDA-approved on/off dosing regimen administered in 28-day cycles, in people with ALS over 48 weeks. A pre-planned futility analysis, conducted after 50% of the planned study population (N=190) reached 48 weeks, assessed the study’s primary endpoint and the probability of the study results changing if all participants completed the 48-week study period. Through that interim analysis, the IDMC concluded that there is a low statistical probability for the investigational once-daily dosing regimen to show superiority to the current on/off dosing regimen as measured by the ALS Functional Rating Scale Revised (ALSFRS-R) score at study completion; therefore, study discontinuation was recommended by the IDMC.
Preliminary findings of the futility analysis suggest that the efficacy of the FDA-approved on/off dosing regimen of oral edaravone was consistent with results of the pivotal Phase 3 trial (MCI186-19 or Study 19) that supported the FDA approval.1,2 MT-1186-A02 found no new safety concerns.
“Research in ALS has always been extraordinarily difficult, but our continued efforts to advance our knowledge is critical to discover the full potential of oral edaravone as an approved treatment for people with ALS. Our learnings from this study will support further research, including real-world evidence and biomarker data generation,” said Gustavo A. Suarez Zambrano, M.D., Vice President of Medical Affairs at MTPA. “We are incredibly grateful to all the study participants, investigators, caregivers and clinical trial staff for their participation, as we remain steadfastly committed to the ALS community.”
Based on the results of the pre-planned futility analysis, the FDA released MTPA of its postmarketing commitment. MTPA is notifying all clinical trial investigators and study sites involved in MT-1186-A02 of these interim findings. Once the remaining data are collected and analyzed, the results will be communicated at a future date. As part of this decision, the global, multi-center, double-blind, Phase 3b MT-1186-A04 study, an extension to MT-1186-A02, will also be discontinued.
About RADICAVA® (edaravone) and RADICAVA ORS® (edaravone)
The U.S. Food and Drug Administration (FDA) approved RADICAVA® (edaravone) on May 5, 2017, and RADICAVA ORS® (edaravone) on May 12, 2022, for the treatment of amyotrophic lateral sclerosis (ALS). RADICAVA is administered in 28-day cycles by intravenous (IV) infusion. It takes 60 minutes to receive each 60 mg dose. For the initial cycle, the treatment is infused daily for 14 consecutive days, followed by a two-week drug-free period. All cycles thereafter are infused daily for 10 days within a 14-day period, followed by a two-week drug-free period. RADICAVA ORS is taken daily for 14 consecutive days followed by a 14-day drug-free period for the initial treatment cycle. For subsequent treatment cycles, RADICAVA ORS is taken for 10 days within a 14-day period followed by a 14-day drug-free period. RADICAVA ORS should be taken in the morning after overnight fasting. Patients should not eat or drink (except water) within one hour after taking RADICAVA ORS.1
Edaravone was discovered and developed for ALS by Mitsubishi Tanabe Pharma Corporation (MTPC) and commercialized in the U.S. by Mitsubishi Tanabe Pharma America, Inc. (MTPA). The MTPC group companies began researching ALS in 2001 through an iterative clinical platform over a 13-year period. In 2015, edaravone was approved as RADICUT® for the treatment of ALS in Japan and South Korea. Marketing authorizations were subsequently granted in Canada (October 2018), Switzerland (January 2019), Indonesia (July 2020), Thailand (April 2021) and Malaysia (December 2021). Marketing authorization for RADICAVA® Oral Suspension was granted in Canada (November 2022) and Switzerland (May 2023), and RADICUT® Oral Suspension 2.1% was granted regulatory approval in Japan in December 2022. To date, in the U.S., RADICAVA and RADICAVA ORS have been used to treat over 12,000 people with ALS, with over 1.45-million days of therapy, and have been prescribed by over 2,100 HCPs.3-5
IMPORTANT SAFETY INFORMATION
Hypersensitivity Reactions
RADICAVA (edaravone) and RADICAVA ORS (edaravone) are contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients of this product. Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have occurred with RADICAVA.
Patients should be monitored carefully for hypersensitivity reactions. If hypersensitivity reactions occur, discontinue RADICAVA or RADICAVA ORS, treat per standard of care, and monitor until the condition resolves.
Sulfite Allergic Reactions
RADICAVA and RADICAVA ORS contain sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown but occurs more frequently in asthmatic people.
Adverse Reactions
The most common adverse reactions (≥10%) reported in RADICAVA-treated patients were contusion (15%), gait disturbance (13%), and headache (10%). In an open label study, fatigue was also observed in 7.6% of patients receiving RADICAVA ORS.
Pregnancy
Based on animal data, RADICAVA and RADICAVA ORS may cause fetal harm.
To report suspected adverse reactions or product complaints, contact Mitsubishi Tanabe Pharma America, Inc., at 1-888-292-0058. You may also report suspected adverse reactions to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
INDICATION
RADICAVA and RADICAVA ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS).
For more information, including full Prescribing Information, please visit www.RADICAVA.com.
About Mitsubishi Tanabe Pharma America, Inc.
Based in Jersey City, N.J., Mitsubishi Tanabe Pharma America, Inc. (MTPA) is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC). It was established by MTPC to develop and advance our pipeline as well as commercialize approved pharmaceutical products in North America. For more information, please visit www.mt-pharma-america.com or follow us on Twitter, Facebook and LinkedIn.
About Mitsubishi Tanabe Pharma Corporation
Mitsubishi Tanabe Pharma Corporation (MTPC), the pharma arm of Mitsubishi Chemical Group (MCG), is one of the oldest pharmaceutical companies in the world, founded in 1678. MTPC is headquartered in Doshomachi, Osaka, the birthplace of Japan’s pharmaceutical industry. MCG has positioned health care as its strategic focus in its management policy, “Forging the future”. MTPC sets the MISSION of “Creating hope for all facing illness”. To that end, MTPC is working on the disease areas of central nervous system, immuno-inflammation, diabetes and kidney, and cancer. MTPC is focusing on “precision medicine” to provide drugs with high treatment satisfaction and additionally working to develop “around the pill solutions” to address specific patient concerns based on therapeutic medicine, including prevention of diseases, pre-symptomatic disease care, prevention of aggravation and prognosis. For more information, go to https://www.mt-pharma.co.jp/e/.
Media inquiries:
Media_MTPA@mt-pharma-us.com
1 RADICAVA and RADICAVA ORS Prescribing Information. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc.; 2022.
2 Edaravone (MCI-186) ALS 19 Study Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(7):505-512.
3 Data on file. Mitsubishi Tanabe Pharma America, Inc.
4 Data on file. Mitsubishi Tanabe Pharma America, Inc.
5 Data on file. Mitsubishi Tanabe Pharma America, Inc.