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

Therapy fails to show it works better once daily than on/off: Analysis

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by Steve Bryson, PhD |

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Mitsubishi Tanabe Pharma America (MTPA), which had been testing a once-daily regimen of its oral therapy Radicava ORS (edaravone) for amyotrophic lateral sclerosis (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 company press release.

“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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Nearly 2,000 ALS Patients in US Being Treated With Radicava ORS

Post-marketing study fulfills MTPA commitment to FDA

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 earned FDA approval in 2017, and the oral formulation was approved in the U.S. 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’s approval of Radicava ORS was supported by clinical trial results 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 Phase 3b MT-1186-A02 study (NCT04569084) 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 enrolled 384 ALS patients, 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’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.

Our learnings from this study will support further research, including real-world evidence and biomarker data generation.

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 Phase 3b MT-1186-A04 trial (NCT05151471), also will be canceled. Complete trial data will be communicated at a future date, the company noted in its release.