Mitsubishi Tanabe’s Radicava (edaravone) is currently one of only two approved disease-modifying therapies (DMTs) for amyotrophic lateral sclerosis (ALS), having been approved by the US Food and Drug Administration (FDA) in 2017. Key opinion leaders (KOLs) previously interviewed by GlobalData, however, expressed concerns over whether the benefits of Radicava treatment are outweighed by its intense dosing schedule, intravenous (IV) route of administration, side effect profile and high annual cost of therapy (ACOT).

Given the importance of Radicava in the treatment algorithm for ALS, as well as its limitations, it is not surprising that edaravone was one of the hot topics in ALS at the recent American Academy of Neurology (AAN) 2022 annual meeting, with five abstracts on the topic. This included both further data on the benefits of Radicava treatment and data on the development of a novel oral formulation of edaravone, MT-1186.

During the session ‘P2: Neuromuscular Disease: Amyotrophic Lateral Sclerosis 2’, data presented from real-world analysis from a US Administrative Claims Database showed that continued use of Radicava resulted in increased overall survival among ALS patients: the risk of death during the analysed timeframe was 27% lower in patients who had received Radicava versus patients who had not. Although this data bolsters the known modest benefits of Radicava treatment in ALS, the product may soon begin to struggle with increased competition from generics, as its patent expiration is expected in 2024 in the US, and cannibalisation from an upcoming oral formulation of edaravone.

A key limitation of Radicava is its IV administration. This requires patients to visit an infusion centre, which may be difficult for patients who are suffering from mobility issues, and thus could result in patients being unwilling to start therapy. As such, Mitsubishi Tanabe is developing an oral formulation of edaravone, MT-1186, which will not only help to increase the number of patients willing to take the drug through a more convenient route of administration, but is also expected to have a lower ACOT and fewer side effects.

The development of this novel formulation of edaravone is also a key strategy from Mitsubishi Tanabe to extend the life cycle of the drug, with the IV formulation facing patent expiry in 2024. During a session at AAN 2022 (P1: Neuromuscular Disease: Amyotrophic Lateral Sclerosis 1), 24-week data from a Phase III safety study of MT-1186 (NCT04165824) was presented. The study found that, overall, MT-1186 was well-tolerated, with a side effect profile consistent with other clinical trials on Radicava.

Although this pivotal clinical trial for MT-1186 is ongoing, with a total treatment period of 48 weeks, the FDA has already accepted Mitsubishi’s new drug application for the drug based on the interim 24-week data, with a Prescription Drug User Fee Act (PDUFA) action date of 12 May. GlobalData expects that when it launches, MT-1186 will gain a significant portion of the ALS market, with global sales of $180m forecast by 2029. In contrast, GlobalData forecasts that, with the entry of generics, IV Radicava will experience a decline in global sales from peak sales of $293m in 2024 to $160m in 2029.