Patient trials under way on ALS treatment to support breathing capacity

The REFALS trial is studying the effects of oral levosimendan in patients with amyotrophic lateral sclerosis (ALS).

Levosimendan, a proprietary medicinal product developed by Orion, has already been used for the treatment of acute decompensated heart failure for a long time. The idea of using levosimendan for the treatment of ALS symptoms arose when its effects were studied more extensively in both preclinical studies and on healthy volunteers, and it was found to improve not only cardiac but also diaphragmatic contractility.

According to Orion’s medical specialist, Valtteri Aho, MD, the discovery encouraged the researchers to study the use of levosimendan in the treatment of ALS. Poor respiratory function is one of the biggest challenges in ALS and a major cause of disability, fatigue, morbidity and - eventually - mortality in ALS.

“There is no cure for ALS, and levosimendan will not stop its progress either. However, we want to help support the patients’ respiratory function and in this way enhance their daily function. There is currently no efficacious medicinal treatment for the respiratory problems, and patients have to rely on assisted ventilation when the symptoms get worse.”

Patient recruitment has been completed

Orion’s LEVALS pilot study with 66 patients was completed in 2017. Although the primary endpoint of the trial was not met, supine slow vital capacity (SVC), which reflects respiratory function, improved after two weeks of treatment in a significant and clinically relevant manner.

“We used two different dosages of levosimendan, both of which produced a significantly better response than placebo. After the double-blind stage, the pilot then continued as an open extension for six months, which provided us with information about the good tolerability of the treatment.”

Encouraged by the positive results, Orion launched the extensive REFALS phase 3 study on 450 patients in summer 2018 with the aim of applying for marketing authorisation. A total of 104 study centres in North America, Europe and Australia are responsible for treating the patients.

“The patients had ALS symptoms for 1 to 4 years and a measurable decline in respiratory function even if they didn’t have actual respiratory symptoms at the time of recruitment. But they must not have been using assisted ventilation yet,” Aho says.

“The trial will last for about one year. The primary variable will be supine SVC reflecting respiratory function. Questionnaires will also be used to find out the patients’ overall functionality and symptoms. The effects of levosimendan and placebo on these variables will be compared.”

After the 12-month trial, the patients will be able to continue the levosimendan treatment in an open extension trial as long as necessary.

A major effort for Orion

As a medical specialist, Valtteri Aho is responsible for the medical quality of the trial.

“I have participated in the planning from the very beginning and cooperated with the authorities and research ethics committees. Instructing and training the study centres taking part in the trial is also a central part of my job,” he says.

“I work in close cooperation with the study sites advising on medical questions, for example those related to patient enrolment. I will also closely monitor any new information that arises during the trial, especially with regard to the safety of the treatment.”

Aho has worked at Orion for over ten years now with proprietary products.

“This is a relatively large clinical trial, which we are running on our own. We’ll do our best to make it a success for both our patients and at the study centres. Our aim is to visit every study site to gain a true picture of how the trial is being conducted in practice, which will allow us to assist in any challenges they are facing.”

 

Study locations

A list of study locations is available at clinicaltrials.gov

 

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