Radicava

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What is it?

Radicava is a trade name of the Mitsubishi Tanabe Pharma Corporation for edaravone, which is a powerful antioxidant. It was originally developed in Japan to help stroke patients recover and is thought to limit oxidative stress on neurons, which is believed to be one of the factors that kills motor neurons in people with ALS. 


The evidence of its effectiveness is certainly not overwhelming, but despite that in 2017 it became the second drug approved to treat ALS in the U.S. Given the high cost and burden of administering the treatment I wanted to review all the ALS-related trials for this drug but I couldn't find a source that did that. Here is my summary of them all, in order of most recent to first:

Trials 4 & 5

Trial Name: 

Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (Trial 4) and a follow-on study (Trial 5)


ClinicalTrials.gov Identifier:

NCT01492686 (Trial 4 only)


Summary: 

Trial 4 involved 137 patients and was completed in October 2014. The approval of Radicava as a treatment was based primarily on the Trial 4 results. A 24-week follow-on study period was added for 123 Trial 4 alumni, which I've called Trial 5. This extended study doesn't appear to be listed on ClinicalTrials.gov or have a separate NCT#, but is written up here


Effectiveness as measured by ALSFRS-R score change

In Trial 4, 137 patients completed the observation period. Of those, 69 were randomly assigned to receive Radicava, and 68 were randomly assigned to receive placebo. The 68 patients taking Radicava (we'll call them Group 1) and 66 taking placebo (Group 2) were included in the primary efficacy analysis, which was change in ALSFRS-R score. The average change in ALSFRS-R  score was -5.01 in Group 1 and -7.50 in Group 2 over 24 weeks. The difference between groups was 2.49 in favor of Radicava.


Trial 5 was the 24-week follow on study period where 123 patients that finished Trial 4 were allowed to continue on Radicava. The difference in ALSFRS-R scores continued to increase to 4.1 points total at week 48 from baseline at week 0, further in favor of Radicava. The group with 48 weeks of continued treatment (Group 1) had a total change of -10.16  and Group 2 (24 weeks placebo + 24 weeks of treatment) had a total change of  -14.33.


Effectiveness as measured by change in FVC%: 

I haven’t found FVC values for Trial 4 alone, but at the end of 24 weeks of treatment in the extended study (equaling 48 total weeks for Trials 4 & 5 combined), Group 1 had a total change of -28.24% while Group 2 had a change of -40.12%  from baseline at week 0.  That is an 11.88% difference in favor of continued Radicava treatment.


Safety: 

In Trial 4, the percentage of patients in Group 1 and Group 2 reporting adverse events during the trial was exactly the same at 84%, indicating the drug was no worse than the placebo. 

Radicava Trial 3, 2, and 1

I will be adding more information on these trials soon.