In ALS, early Radicava lowers risk of ventilation, hospitalization, mortality

Study 19 patients who started on Radicava had slower disease progression

by Patricia Inácio, PhD | August 15, 2023

Early treatment with Radicava (edaravone), an approved therapy for amyotrophic lateral sclerosis (ALS), significantly reduced the risk of hospitalization, need for ventilatory support, or death compared with delaying treatment for six months.

That’s according to analyses of data from Study 19 (NCT01492686), the Phase 3 clinical trial that supported Radicava’s approval, and its open-label extension.

Patients initially assigned to Radicava in the Phase 3 trial tended to have better survival outcomes as well as a lower risk of death or need for ventilation than those who started it in the extension. These results failed to reach statistical significance, however.

“This analysis illustrates the importance of earlier and continued treatment with [Radicava] for patients with ALS in the clinical setting,” the researchers wrote in “The effects of intervention with intravenous edaravone in Study 19 on hospitalization, tracheostomy, ventilation, and death in patients with amyotrophic lateral sclerosis,” which was published in Muscle & Nerve.

Radicava, infused directly into the bloodstream, was approved in the U.S. for ALS in 2017. It’s designed to decrease oxidative stress, a type of cellular damage that’s believed to contribute to nerve cell death in the disease. More recently, the treatment became available as an oral suspension formulation called Radicava ORS.

Radicava’s approval was based on data from Study 19, a clinical trial in Japan that enrolled 137 people with ALS and randomly assigned them to Radicava or a placebo for 24 weeks. The patients who started Radicava earlier continued to have a slower disease progression than those who transitioned from a placebo.

After six months, those given Radicava saw a significantly slower decline in their ability to perform everyday activities, by 33%, over the placebo group.

After completing the randomized part, patients could join an open-label extension (OLE), where all received Radicava for 24 weeks to assess its long-term effectiveness. Those who started it earlier continued to have a slower disease progression than those who transitioned from a placebo.

A team led by researchers at Mitsubishi Tanabe Pharma, the developer of Radicava formulations, conducted a post hoc analysis — or one done after the trial is over and all the results have been gathered — to examine survival and other disease milestones with participants in Study 19 and its OLE.

The analysis included 65 patients who were always on Radicava and 58 who initially received a placebo for 24 weeks and then switched to Radicava until week 48. Almost a third (23%) of those assigned first to Radicava and 41% originally on a placebo discontinued treatment over the 48 weeks.

While no deaths were registered in the 24-week period, two patients always on Radicava and four who started on a placebo died during the OLE. The risk of death was lowered by 52% in the continuous Radicava group, but the findings were not significant, the analyses suggested.

Similarly, starting Radicava earlier tended to extend the time to death, the need for a tube in the neck to help with breathing, or tracheostomy, or the need for permanent assisted ventilation, but that also failed to reach significance.

When the researchers examined the combined risk of events such as death, tracheostomy, permanent assisted ventilation, or hospitalization, there was a significant difference, however. Those continuously on Radicava were 53% less likely to have any of those events over those who started it six months later.

This difference in risk was mainly driven by hospitalizations, the researchers noted. Hospitalizations occurred in 38.2% of those first given a placebo, compared with 27.5% with those always on Radicava.

The findings show into-the-vein Radicava is “associated with a lower rate of death, tracheostomy, PAV [permanent assisted ventilation], or hospitalization during the 48-week trial,” the researchers said, noting more research was recommended to confirm the results.