Finnish drugmaker Orion Pharma is pressing ahead with a pivotal trial for its amyotrophic lateral sclerosis drug ODM-109, despite mixed results in a phase 2 trial.
The first patients have now been recruited into its phase 3 trial of ODM-109—an oral formulation of Orion’s heart failure drug Simdax (levosimendan)—in the hope of showing that it can help support breathing function in patients with the devastating neurodegenerative disease.
Orion said it plans to enroll 450 subjects in the placebo-controlled trial at sites in Europe, North America and Australia, with patients taking the drug for a year to see if it can slow down the respiratory difficulties that are the usual cause of death in ALS.
In a phase 2 trial involving 66 ALS patients, ODM-109 missed its primary endpoint of an improvement in sitting slow vital capacity (SVC)—a measure of lung function—but was able to improve SVC when patients were lying on their backs.
“If the results of the [phase 3] trial are positive, the aim is to file for marketing authorization in the U.S. and Europe,” according to Orion. Results from the study are due in 2020.
For years, ALS only had one FDA-approved therapy—Sanofi’s Rilutek (riluzole)—which has limited efficacy, with most patients still dying three to five years after diagnosis. In 2017, Mitsubishi Tanabe got FDA approval for free radical scavenger Radicava (edaravone), after filing the drug at the agency’s request, based on a six-month study that showed a slower decline in physical function compared to placebo.
Not all are convinced by the data for Radicava just yet, however, and it’s widely recognized that other new therapies are desperately needed that can definitively slow down the loss of function in ALS.
Prospects for a new therapy for ALS took a big knock last year after the high-profile failure in phase 3 of Cytokinetics’ tirasemtiv, despite major tweaks to the trial protocol, but the company is hoping a clutch of new drugs, along with ODM-019, could end the drought.
Another European biotech, France’s AB Science, had a marketing application for its masitinib drug for ALS provisionally turned down in Europe in April, with regulators saying a phase 2/3 trial that showed efficacy at the highest dose used wasn’t sufficient to support approval. The company has filed additional information to the EMA and is planning a confirmatory trial that it hopes will also support a U.S. filing.
Meanwhile, some of the other players in the field include Biogen and Ionis, which have a SOD1-targeting antisense drug called BIIB067 in phase 1/2 trials, Amylyx with AMX0035 (sodium phenylbutyrate and tauroursodeoxycholic acid) in phase 2 with results due later this year, and new startup QurAlis. Another company active in this area is Brainstorm Cell Therapeutics, which has stem cell-based NurOwn in phase 3 for ALS after showing a benefit in mid-stage testing.