FDA Approves Oral Version of Edaravone for ALS

The FDA has approved an oral formulation of edaravone, marketed as Radicava ORS (Mitsubishi Tanabe Pharma America), for the treatment of amyotrophic lateral sclerosis (ALS). The formulation, which can be given by mouth or feeding tube, expands upon the usage of a previously approved intravenous version.

The drug, which is meant to slow loss of physical function in ALS, can now be administered in several ways to best accomodate the different needs of patients with ALS.

“ALS is a progressive disease that, due to its heterogenous nature, impacts patients at different rates with varying symptoms,” said Tulio Bertorini, MD, professor of neurology, The University of Tennessee Health Science Center, in a statement. “Therefore, it is crucial that patients have treatment and formulation options that accommodate their own unique needs, and Radicava ORS provides HCPs who have prescribed their ALS patients edaravone with an alternate delivery option.”

The new oral formulation—which offers the same efficacy as the intravenous version—is designed for ease of use, with a 5 mL dose contained in a portable bottle that does not require refrigeration or reconstitution.

The approval is supported by evidence from the IV edaravone phase 3 pivotal trial, Study 19 (NCT01492686), which evaluated 137 patients with ALS, demonstrating that treatment with edaravone slowed loss of physical function by 33% compared with placebo at 24 weeks based on the ALS Functional Rating Scale-Revised. Additional safety and efficacy data were collected from several phase 1 trials as well as an additional global phase 3 trial (NCT04165824). An ongoing phase 3 study (NCT04577404) is also examining the long-term safety and tolerbility of oral edaravone over 96 weeks.

The original intravenous formulation was FDA-approved on May 5, 2017, and is administered in 28-day cycles, with each patient receiving a 60 mg dose over the course of a 60-minute infusion. The oral formulation requires a 14-day induction period of daily administration followed by a 2-week drug-free period. This initial cycle is followed by a 10-day treatment cycle every 14 days, which is followed by a 14-day drug-free period.

The most common adverse events associated with edaravone are bruising, gait disturbances, and headache, as well as fatigue.

In addition to the ongoing long-term phase 3 trial, Mitsubishi Tanabe has also recently launched the phase 4 REFINE-ALS trial (NCT04259255), which is anticipated to enroll approximately 300 patients with ALS who have begun treatment with edaravone. The 24-week study will include a total of 6 treatment cycles, each spanning 28 days, with 60 mg of edaravone administered by IV infusion for 14 days of the initial treatment cycle and followed by daily dosing on 10 out of 14 days in subsequent cycles. Biomarkers will be assessed for oxidative stress, inflammation, and neuronal and muscle injury, prior to treatment initiation, at treatment start, and again at cycles 1, 3, and 6 over the course of the study period.

Mitsubishi Tanabe Pharma's new drug application for oral edaravone was accepted for priority review by the FDA on January 24, 2022. The drug also received orphan drug and fast track designations.

REFERENCE

Mitsubishi Tanabe Pharma America Announces FDA Approval of RADICAVA ORS® (edaravone) for the Treatment of ALS. News release. Mitsubishi Tanabe Pharma America. May 13, 2022. https://www.prnewswire.com/news-releases/mitsubishi-tanabe-pharma-america-announces-fda-approval-of-radicava-ors-edaravone-for-the-treatment-of-als-301546937.html