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<a href="https://www.mt-pharma-america.com/">Mitsubishi Tanabe Pharma America</a> (MTPA), which had been testing a once-daily regimen of its oral therapy <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava ORS</a> (edaravone) for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), announced that it is discontinuing the Phase 3b trial and its extension study.
That decision comes after an interim analysis by an independent data monitoring committee (IDMC) showed the once-daily treatment is not likely to work better than the approved on/off regimen.
Still, the IDMC’s recommendation to stop the study was not due to safety or efficacy concerns, and this decision will not impact the commercial availability of Radicava ORS, according to the company.
“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,” Gustavo A. Suarez Zambrano, MD, MTPA’s vice president of medical affairs, said in a <a href="https://www.mt-pharma-america.com/media/news/press-releases/2023/07/31/mitsubishi-tanabe-pharma-america-announces-update-on-global-phase-3b-mt-1186-a02-postmarketing-study-of-oral-edaravone-in-als">company press release</a>.
“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,” Suarez Zambrano added.
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<h3>Post-marketing study fulfills MTPA commitment to FDA</h3>
Edaravone, the active ingredient in Radicava and Radicava ORS, is designed to offset oxidative stress, a type of cellular damage implicated in ALS. The therapy aims to prevent damage to motor neurons — nerve cells that control body movement — thereby slowing disease progression.
The into-the-vein (intravenous) formulation of Radicava <a href="https://alsnewstoday.com/news/fda-approves-radicava-first-new-als-therapy-in-20-years-and-cause-for-hope/">earned</a> FDA approval in 2017, and the oral formulation was <a href="https://alsnewstoday.com/news/fda-approves-radicava-ors-oral-suspension-edaravone-als/">approved in the U.S.</a> last year. A liquid suspension taken either orally or via a feeding tube, Radicava ORS was designed to offer the same efficacy as the original therapy but in a more convenient and less burdensome formulation for patients.
Both are given in 28-week or roughly seven-month cycles. In an initial treatment cycle, patients receive daily treatment for 14 consecutive days, followed by two weeks without treatment. Then, the therapies are taken daily over 10 of the next 14 days, followed by another two-week break.
The FDA&#8217;s approval of Radicava ORS was supported by <a href="https://alsnewstoday.com/news/als-treatment-radicava-ors-fares-well-phase-3-clinical-trial/">clinical trial results</a> demonstrating that 105 mg of the oral formulation delivered similar amounts of edaravone to the body and had the same efficacy in slowing disease progression as the 60 mg used in the intravenous version.
The now-discontinued <a href="https://clinicaltrials.gov/ct2/show/NCT04569084">Phase 3b MT-1186-A02 study (NCT04569084)</a> was conducted to fulfill a post-marketing commitment that MTPA made to the FDA after the regulatory agency approved Radicava’s intravenous formulation. It was designed to evaluate the approved Radicava ORS on/off dosing regimen versus once-daily dosing.
The study <a href="https://alsnewstoday.com/news/post-marketing-als-trial-approved-radicava-ors-fully-enrolled/">enrolled 384 ALS patients</a>, ages 18-75, whose symptoms had started less than two years prior. The trial’s main goal was to evaluate changes in disease progression, as assessed by the ALS Functional Rating Scale-Revised (ALSFRS-R), over 48 weeks, or about one year.
The trial&#8217;s IDMC conducted its pre-planned interim analysis after 190 patients — half of the planned study population — reached the 48-week assessment.
Based on the interim data from the primary endpoint, the IDMC concluded that there is a low statistical probability for the once-daily dosing regimen to be more effective than the current on/off regimen. As a result, study discontinuation was recommended.
[quote=&#8221;center&#8221;]Our learnings from this study will support further research, including real-world evidence and biomarker data generation.[/quote]
Nonetheless, the preliminary data did show that the efficacy of the on/off dosing regimen of Radicava ORS was consistent with data from the clinical trials that supported FDA approval of both Radicava formulations. Also, no new safety concerns were reported.
“Our learnings from this study will support further research, including real-world evidence and biomarker data generation,” Suarez Zambrano said.
Supported by the findings, MTPA was released from its post-marketing commitment to the FDA. The company is now notifying trial investigators at study sites of these findings.
MT-1186-A02’s extension study, the <a href="https://classic.clinicaltrials.gov/ct2/show/NCT05151471">Phase 3b MT-1186-A04 trial (NCT05151471)</a>, also will be canceled. Complete trial data will be communicated at a future date, the company noted in its release.

MTPA to stop Phase 3 trial of approved Radicava ORS for ALS

A Phase 3b study evaluating the long-term safety and effectiveness of two dosing regimens of <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava ORS</a> (edaravone) — an approved oral formulation of the medicine — in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) is now fully enrolled.
The study was designed to fulfill a post-marketing commitment that <a href="https://www.mt-pharma-america.com/">Mitsubishi Tanabe Pharma America</a> (MTPA) made to the U.S. Food and and Drug Administration (FDA) after the regulatory agency <a href="https://alsnewstoday.com/news/fda-approves-radicava-first-new-als-therapy-in-20-years-and-cause-for-hope/">approved</a> the into-the-vein (intravenous) formulation of Radicava in 2017.
The medication&#8217;s oral formulation, Radicava ORS, <a href="https://alsnewstoday.com/news/fda-approves-radicava-ors-oral-suspension-edaravone-als/">earned</a> its U.S. approval in 2022.
&#8220;We&#8217;re very pleased to announce the completion of trial enrollment in our Phase 3b study of Radicava ORS, representing an important achievement in our ongoing commitment to the fight against ALS,&#8221; Atsushi Fujimoto, president of MTPA, said in a <a href="https://www.prnewswire.com/news-releases/mitsubishi-tanabe-pharma-america-announces-enrollment-completion-for-global-phase-3b-study-of-radicava-ors-edaravone-in-als-301779833.html">company press release</a>.
&#8220;We are deeply grateful to the study participants and their families, as well as study investigators and clinical staff for working so diligently to help us meet this milestone,&#8221; Fujimoto added.
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<h3>Phase 3b study testing 2 different doses of oral therapy</h3>
Radicava ORS is a liquid suspension taken either orally or via a feeding tube. As with the intravenous formulation, it is given in 28-day cycles.
The first cycle consists of daily treatment for 14 days followed by a two-week period (a second 14 days) without the medication. In subsequent cycles, Radicava is taken daily for 10 of the next 14 days, followed again by two weeks without treatment.
Approval of Radicava ORS was based on <a href="https://alsnewstoday.com/news/als-treatment-radicava-ors-fares-well-phase-3-clinical-trial/">clinical trial data</a> indicating that a 105 mg dose of the oral treatment delivers similar amounts of edaravone — Radicava&#8217;s active ingredient — to the body and is as good at slowing disease progression as the intravenous version (60 mg).
Now, the global <a href="https://clinicaltrials.gov/ct2/show/NCT04569084">MT-1186-A02 study (NCT04569084)</a> is designed to compare the approved Radicava ORS on/off dosing regimen against once-daily dosing.
A total of 384 ALS patients, ages 18-75, whose symptoms emerged in the two years prior to the trial, were enrolled across 80 sites in the U.S., Canada, Europe, and Asia.
After an eight-week screening period, participants will either receive Radicava ORS every day, or be given the medication and a placebo. In the medication/placebo group, patients will receive Radicava ORS for 14 days and a placebo for 14 days in the first 28-day cycle, followed by 10 days of treatment and 18 days on a placebo for the next cycles.
The trial&#8217;s main goal is to evaluate changes in disease progression, as assessed by the ALS Functional Rating Scale-Revised (ALSFRS-R), over 48 weeks, or nearly one year. Secondary goals include changes in lung function and in measures of patient-reported quality of life, as well as the time patients live without requiring ventilatory support.
Top-line results from the trial, which already is underway, are expected in 2024.
&#8220;We look forward to seeing how the results of this study evaluating an alternative dosing regimen for Radicava ORS build upon our existing data to support its long-term efficacy and safety profile for people living with ALS, and how it may increase our understanding of the full potential of the medication as a treatment option,&#8221; said Michael D. Weiss, MD, of the University of Washington Medical Center, who is the study&#8217;s lead investigator.
Radicava works by combating oxidative stress, a type of cellular damage that&#8217;s been implicated in ALS. In doing so, it&#8217;s expected to protect nerve cells from damage and slow disease progression.
Intravenous Radicava also is approved in Japan, South Korea, Canada, and Switzerland, among other countries. The oral version has approvals in the U.S., Canada, and Japan.

Tag: post-marketing study

MTPA to stop Phase 3 trial of approved Radicava ORS for ALS

Post-marketing trial of 2 Radicava ORS doses now fully enrolled