Mitsubishi Tanabe Pharma America Presents Interim Data from REFINE-ALS Biomarker Study at 21st Annual NEALS Meeting

Study Results May Help to Identify Monitoring Biomarkers of ALS as well as Predictive Biomarkers to Measure the Effect of RADICAVA^® (edaravone)

JERSEY CITY, N.J., Nov. 2, 2022 /PRNewswire/ -- Mitsubishi Tanabe Pharma America, Inc. (MTPA) today announced the presentation of an interim analysis of the Phase 4 REFINE-ALS study, designed to identify predictive and pharmacodynamic biomarkers to measure the effect of  RADICAVA^® (edaravone) in people with amyotrophic lateral sclerosis (ALS). The results will be presented as part of the 21^st Annual Northeast Amyotrophic Lateral Sclerosis (NEALS) Meeting, being held in Clearwater, Fla., from November 1-3.

"The REFINE-ALS study has enabled us to examine meaningful biomarkers to enhance our understanding of the complexities of ALS and the role that edaravone might play in treatment of the disease," said Gustavo A. Suarez Zambrano, M.D., Vice President of Medical Affairs at MTPA. "We are encouraged by these initial findings and look forward to gathering more biomarker data on these important assessments and sharing our key learnings with the ALS community."

REFINE-ALS, conducted in collaboration with the Neurological Clinical Research Institute (NCRI) at Massachusetts General Hospital (MGH), is a prospective, observational, multi-center study in people with ALS in the U.S. and Canada who initiated treatment with RADICAVA. The study includes assessments of biomarkers of oxidative stress, inflammation and neuronal injury and death, as well as biomarker discovery panels, EpiSwitch^™ and SOMAscan^®, designed to identify and evaluate epigenetic and protein biomarkers, respectively. Baseline biomarker measurements are taken prior to starting treatment with RADICAVA, at the start of treatment and at pre-specified longitudinal time points throughout the 24-week study period.

As of April 2022, a total of 50 participants were enrolled in the study and matched with 36 participants from the Answer ALS study, a research project led by a collaborative team including the MGH NCRI. Biomarker and clinical data from 40 participants were included in this interim analysis, with the following findings:

• At baseline, the proportion of fast progressors, as predicted by EpiSwitch^™, were numerically higher in REFINE-ALS participants compared with the Answer ALS participants.
• At baseline, neurofilament light chain (NfL) levels were numerically higher in REFINE-ALS participants (n=38) compared with the Answer ALS participants (n=35). Additionally, as hypothesized, NfL levels were found to correlate with the rate of disease progression as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).
• Despite a higher proportion of EpiSwitch^™ "fast" predictions and higher baseline NfL for REFINE-ALS participants compared to Answer ALS, the Answer ALS and REFINE-ALS cohorts progressed at the same rate on ALSFRS-R score.

"We have a seen a heightened interest in leveraging biomarker research in ALS to evaluate potential relationships between changes in biomarkers and disease progression and treatment outcomes," said primary investigator James Berry, M.D., M.P.H., MGH NCRI, Boston. "The results from REFINE-ALS may help provide further insight into the biological effect of edaravone treatment of ALS using biomarkers. Our hope is that continued ALS biomarker research will serve as an important tool for understanding treatment effects in ALS."

REFINE-ALS is a NEALS-affiliated clinical trial sponsored by MTPA.

About RADICAVA^® (edaravone) and RADICAVA ORS^® (edaravone)
The U.S. Food and Drug Administration (FDA) approved RADICAVA^® (edaravone) on May 5, 2017, and the oral formulation RADICAVA ORS^® (edaravone) on May 12, 2022, for the treatment of amyotrophic lateral sclerosis (ALS). RADICAVA is administered in 28-day cycles by 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 Mitsubishi Tanabe Pharma Development America, Inc. (MTDA), 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, RADICAVA was approved for the treatment of ALS in Japan and South Korea. Marketing authorizations were subsequently granted in Canada (October 2018), Switzerland (January 2019), China (July 2019), Indonesia (July 2020), Thailand (April 2021) and Malaysia (December 2021). To date, in the U.S., RADICAVA and RADICAVA ORS have been used to treat over 8,000 patients, with over 1.1-million days of therapy, and have been prescribed by nearly 2,000 HCPs.^2,3

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's (MTPC) 100 percent owned U.S. holding company, Mitsubishi Tanabe Pharma Holdings America, Inc. It was established by MTPC to 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 Development America, Inc.
The U.S. headquarters of Mitsubishi Tanabe Pharma Development America, Inc. (MTDA) is located in Jersey City, New Jersey. MTDA is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation's 100 percent-owned U.S. holding company, Mitsubishi Tanabe Pharma Holdings America, Inc. For more information, please visit https://mt-pharma-development-america.com/.

About Mitsubishi Tanabe Pharma Corporation
Mitsubishi Tanabe Pharma Corporation (MTPC), the pharma arm of the Mitsubishi Chemical Group, is one of the oldest pharmaceutical companies in the world, founded in 1678, and focusing on ethical pharmaceuticals. MTPC is headquartered in Doshomachi, Osaka, the birthplace of Japan's pharmaceutical industry. The Mitsubishi Chemical Group 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 prioritizing work on "precision medicine" to provide drugs with high treatment satisfaction by identifying patient populations with high potential for efficacy and safety, focusing on the disease areas of central nervous system and immuno-inflammation. In addition, MTPC is 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/.

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¹ RADICAVA and RADICAVA ORS Prescribing Information. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc.; 2022.
² Data on file. Mitsubishi Tanabe Pharma America, Inc.
³ Data on file. Mitsubishi Tanabe Pharma America, Inc.

SOURCE Mitsubishi Tanabe Pharma America, Inc.