Mitsubishi Tanabe Pharma America Announces Post-Hoc Analysis Examining Effect of Early Intervention with RADICAVA® (edaravone) on Survival and Disease Progression Milestones in People with ALS

Results from this Analysis were Published in Muscle & Nerve

JERSEY CITY, N.J., Aug. 17, 2023 /PRNewswire/ -- Mitsubishi Tanabe Pharma America, Inc. (MTPA) today announced the publication of a post-hoc analysis of the pivotal, Phase 3 study (MCI186-19) reviewing the effect of intravenous (IV) RADICAVA^® (edaravone) on survival and additional disease progression milestone events in people with amyotrophic lateral sclerosis (ALS). Results from the analysis, which were published in Muscle & Nerve, suggest that timely and continued treatment with RADICAVA when initiated first was associated with a lower risk of death, tracheostomy, permanent assisted ventilation (PAV) or hospitalization, compared to people with ALS who received placebo first followed by RADICAVA.

"While the ALSFRS-R is considered the gold standard used to assess ALS progression and treatment efficacy, there is value in exploring other outcome measures, including survival-related events," said Gustavo A. Suarez Zambrano, M.D., Vice President of Medical Affairs at MTPA. "This post-hoc analysis of our Phase 3 MCI186-19 study allows us to grow our understanding of the benefit of starting early and continued treatment with RADICAVA, and is a reflection of our commitment to ensure people with ALS are at the center of everything we do."

The post-hoc analysis assessed the double-blind, placebo-controlled 24-week Phase 3 MCI186-19 study of RADICAVA, including an additional 24-week open-label period with all study participants receiving RADICAVA first (edaravone-edaravone [EE]) vs. placebo first (placebo-edaravone [PE]). Results from the survival analysis showed:

• A 53% relative risk reduction of the cumulative occurrence of milestone events (death, tracheostomy, PAV or hospitalization due to ALS progression) in the EE group vs. PE group, with a hazard ratio of 0.47 (95% CI, 0.25-0.88, p=0.02).
• ALS survival composite endpoint analyses (ALS/SURV) suggested a treatment benefit (least squares mean difference) for the EE group vs. the PE group at week 24 (0.15±0.05 [95% CI, 0.06-0.25] p<0.01) and week 48 (0.11±0.05 [95% CI, 0.02-0.21] p=0.02).
• There were no deaths during the double-blind period. During the open-label period, there were two deaths in the EE group and four in the PE group.

As these results are from a post-hoc analysis, the results should be interpreted with caution. Additionally, this post-hoc analysis relied on data from weeks 24-48 of the MCI186-19 study, which were not placebo controlled and were not adjusted for statistical multiplicity. Results of this analysis have not been replicated in a double-blind, placebo-controlled trial, and no definitive conclusions can be drawn without additional, appropriately controlled clinical studies. Lastly, the MCI186-19 study was not powered a priori to analyze the novel composite endpoint of death, tracheostomy, PAV, or hospitalization. The understanding of these study limitations is critical to proper application of insights.

"The findings of this post-hoc analysis are encouraging," said Benjamin Rix Brooks, M.D., a longtime leader in ALS research and lead author of the study. "These data reinforce the importance of continuing research that can further support an association between earlier use of RADICAVA and the potential impact on survival-related milestones in ALS."

This analysis was funded and conducted 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 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.^2-4

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/.

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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.
⁴ Data on file. Mitsubishi Tanabe Pharma America, Inc.

SOURCE Mitsubishi Tanabe Pharma America, Inc.