Edaravone formulation FAB122 fails to slow ALS progression

Ferrer to cancel open-label extension ADOREXT, following results

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Note: This story was updated Jan 24, 2024, to correct that Radicava and Radicava Oral Suspension are available in Switzerland but not in other European countries.

FAB122, an oral formulation of edaravone developed by Ferrer, failed to slow disease progression or extend survival in adults with amyotrophic lateral sclerosis (ALS) who took part in a Phase 3 clinical trial.

The ADORE trial (NCT05178810), running across dozens of sites in Europe, was testing the formulation against a placebo, given as a daily dose of 100 mg for 48 weeks, on top of the standard of care for ALS.

“We are disappointed with this outcome and would like to thank the people with ALS, caregivers, investigators, and clinical trial staff for their participation in [the] ADORE clinical trial,” Tatjana Naranda, PhD, Ferrer’s chief research and development officer, said in a company press release.

The company will terminate ADOREXT (NCT05866926), an open-label extension to the ADORE trial that was testing the long-term safety of FAB122 for up to three years.

“Although the results are not what we hoped for, our work to advance potentially transformative therapies in areas of high unmet need for people living with ALS will not stop,” Naranda said.

Edaravone protects nerve cells by neutralizing unstable molecules produced during metabolism called reactive oxygen species. When those unstable molecules build up in excess, they can damage nerve cells and contribute to the neurodegeneration seen in ALS.

The medication is available in the U.S. as Radicava, which is infused into the bloodstream, and as Radicava ORS, an oral suspension taken by mouth or via a feeding tube. Except for Switzerland, no European countries have approved either of these therapies.

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What were the goals of the ADORE trial?

FAB122, also called FNP122 and TWoo1, is a distinct formulation of edaravone that’s made of granules packaged in sachets to be dissolved in water. It was developed by the Dutch company Treeway, who licensed it to Ferrer for clinical testing in Europe and some Asian countries.

ADORE recruited about 300 adults, ages 18-80, who’d had their first ALS symptoms within the last two years. It was conducted with the support of Treatment Research Initiative to Cure ALS (TRICALS), an European research initiative.

The trial’s main goal was to determine if adding FAB122 to standard ALS treatment could significantly slow disease progression, as assessed with the Revised ALS Functional Rating Scale (ALSFRS-R). Safety and the treatment’s impact on the Combined Assessment of Function and Survival (CAFS) were secondary measures. CAFS is a composite measure that ranks clinical outcomes based on survival and the rate of ALSFRS-R decline.

The treatment was safe and well tolerated, but failed to slow disease progression at 48 weeks compared with a placebo and didn’t improve CAFS outcomes at 48 and 72 weeks.

“At TRICALS, we had hoped for a different outcome of the ADORE study and are disappointed that this is not the positive result we all wanted,” said Leonard van den Berg, MD, PhD, chair of TRICALS. “We will continue to do our utmost to find a treatment for ALS as soon as possible.” Van den Berg is also professor of neurology at the University Medical Centre Utrecht in the Netherlands and was the trial’s principal investigator.

Mitsubishi Tanabe Pharma America, the developer of Radicava and Radicava ORS, said FAB122 contains a distinct formulation of edaravone than that found in its products.

The clinical trial also had “many significant differences” from the Phase 3 trial that supported Radicava’s approval, so “any data and/or conclusions relative to FNP122 (FAB122) cannot be directly compared to [Radicava] or Radicava ORS,” the company said in a press release.