The filing by Mitsubishi Tanabe Pharma Corp. of a US approval filing for edaravone marks the start of what the mid-sized Japanese firm hopes will be a path to increased sales in a market where it has so far had only a limited direct presence.

The company has applied to the FDA for the approval of the product for use in amyotrophic lateral sclerosis (ALS), in what MTP described as the "first step in accelerating its US business development activities".

The NDA is supported by clinical data from Japan, where edaravone was launched for the inhibition of progression of functional disorders in ALS patients around a year ago, and has been marketed as Radicut since 2001 for various types of acute cerebral infarction.

The free radical-scavenging nootropic and neuroprotective agent was also launched for ALS in South Korea last December, and already has orphan status in this setting in the US and the EU.

The small molecule therapy is thought to relieve the effects of oxidative stress - an imbalance between free radicals and the body's attempts to detoxify these - which is seen as a likely factor in ALS onset and progression, given increases in oxidative stress biomarkers in sufferers.

Oxidative stress in turn is believed to be an outcome of an ischemic environment that leads to the opening of mitochondrial permeability transition pores and eventually causes cell death.

Top-line Phase III results from a 137-patient Japanese study were presented at the American Academy of Neurology meeting this April, which showed less functional loss and quality of life deterioration at six months in treated patients compared to standard of care.

The study met its primary efficacy endpoint of change in ALS Functional Rating Scale-Revised score at week 24, and both groups showed a similar overall incidence of adverse events.

Another abstract presented at the meeting showed benefits for early over later initiation of edaravone therapy.

Laying The Ground

MTP set up a new wholly owned subsidiary in the US, MT Pharma America Inc, in Jersey City, New Jersey, earlier this year, with the aim of conducting in-house sales and marketing activities in this market, initially focusing on edaravone.

All going well, the company is currently expecting a launch sometime in the fiscal year ending March 2017, and a specialist sales force is being built up ahead of that time.

Independent operations and expansion in the US specialty sector form a major pillar of MTP's new mid-term business plan, under which the company is aiming to generate total US sales of JPY80bn ($765m) by March 2021.

MTP does not currently break out its US sales, but has said around JPY200bn will be invested in its US operations over the course of the mid-term plan ([A#28160223004]).

Medical Need

According to data from the US ALS Association cited by MTP, there are around 5,600 diagnoses of ALS (also known as Lou Gehrig's disease) annually in the US, where up to around 30,000 people in total may be affected. The disease is characterized by neuronal degeneration in the brain and spinal cord and voluntary muscle weakness, which can eventually lead to respiratory failure.

ALS is inherited in 5-10% of cases, but causality remains unclear and may also be linked to environmental factors.

Current major therapies include riluzole (Sanofi’s Rilutek and generics), which is thought to inhibit glutamate release and inactivate voltage-dependent sodium channels. Other late-stage candidates include AB Science's platelet-derived growth factor receptor and fibroblast growth factor receptor inhibitor masitinib, and Cytokinetics Inc.'s troponin-targeting tirasemtiv, both now in Phase III, Informa's Biomedtracker shows.

"There is an urgent need for new treatment approaches that may affect the course of this devastating disorder," Dr. Lucie Bruijin, chief scientist of the ALS Association, said in a statement, adding the group is "encouraged by the efforts" of MTP to make its drug available.

Big US Step For Mitsubishi Tanabe As Edaravone Filed For ALS

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