Edaravone

Unassigned

New Medicines

Radicava · Amyotrophic lateral sclerosis (motor neurone disease)

Information

Radicava
New molecular entity
Mitsubishi Tanabe
Mitsubishi Tanabe

Development and Regulatory status

Filing withdrawn
Filing withdrawn
Launched
Yes
Yes

May 19: Mitsubishi Tanabe has withdrawn the EU Marketing Authorisation Application. At the time of withdrawal, and following expert consultation, the CHMP was of the provisional opinion that the drug could not have been approved, because the trial data were insufficient to prove effectiveness. CHMP considered the possibility of Conditional Approval, which mandates the company to provide more supporting data to prove effectiveness, however the company does not appear to have agreed to this route. In view of this, the Committee considered that on the data available, the benefits of the drug did not outweigh its risks [10].


Jun 18: Filed in EU using centralised procedure [9].


Aug 17: Launched in US [8].


May 17: Mitsubishi Tanabe currently has no plans to market edaravone in the EU [7].


May 17: FDA approves edaravone. This makes it the first drug approved in the US for treatment of ALS (also known as Lou Gehrigs disease) since Rilutek in 1995. Approval was granted based on trial results from Japan. Each infusion has a list price of $1,086 (approx annual cost $145,000) [4].


Jun 16: Edaravone has orphan drug status in EU [3].


Jun 16: Filed in US. Has been granted orphan drug status in the US, and its filing is supported by the same data that secured its regulatory approval in Japan and South Korea last year. The PIII trial met its primary endpoint of mean change in the ALS Functional Rating Scale-Revised at 24 weeks versus the standard of care [1].

Category

Free radical scavenger that is believed to relieve the effects of oxidative stress, a likely factor in the onset and progression of ALS.
ALS is the most common form of motor neurone disease; annual incidence of about 2 cases per 100,000 population and prevalence is about 5-7 per 100,000 [2].
Amyotrophic lateral sclerosis (motor neurone disease)
Intravenous infusion

Trial or other data

May 17: FDA granted approval of edaravone (Radicava) based on the 6-month PIII trial results (NCT01492686) from Japan. In the trial, 137 participants were randomised to receive edaravone or placebo. Primary efficacy endpoint was change in ALS Functional Rating Scale-Revised (ALSFRS-R) score at week 24. At Week 24, mean change (±SE) in ALSFRS-R score was -7.50±0.66 (placebo) and -5.01±0.64 (edaravone): a between group difference of 2.49±0.76 (P=0.001). The most common adverse reactions reported by participants receiving edaravone were bruising (contusion), dysphagia and gait disturbance [5,6].


Jun 16: A long-term extension study (NCT00424463) to assess the efficacy and safety of long-term intermittent therapy with edaravone 60mg in patients with ALS in 140 patients in Japan, plus a PIII trial assessing edaravone (60mg, once-daily IV drip) in patients with grade III ALS, based on the changes in ALSFRS-R scores after 24 weeks (NCT00415519) have also been completed [3].


Jun 16: Mitsubishi Tanabe Pharma has previosuly also completed a PIII trial of edaravone in 206 patients with ALS in Japan (NCT00330681). The primary objective was to confirm the efficacy of edaravone (60mg, once-daily IV infusion) in patients with ALS based on changes in ALSFRS-R scores after 24 weeks administration; this study also examined drug safety [3].


Oct 14: A randomised, double-blind placebo-controlled PIII trial investigating efficacy and safety of once-daily edaravone 60mg, given by IV drip, in patients with ALS completes (MCI186-19; NCT01492686). 137 patients were enrolled in Japan. Compared with placebo, there was less functional loss in patients receiving edaravone [3].