Orion Launching Extension Study for ALS Patients Enrolled in Phase 3 REFALS Trial

Amyotrophic lateral sclerosis (ALS) patients who complete the ongoing Phase 3 REFALS clinical trial evaluating levosimendan (also known as ODM-109) will soon have the opportunity to enroll in an open-label extension study.

Levosimendan is an oral treatment developed by Orion that is being investigated for its ability to relieve breathing problems in ALS patients.

The upcoming study, called REFALS-ES, will allow patients to continue treatment with levosimendan for as long as it is needed. The trial will allow researchers to understand the long-term safety and effectiveness of the treatment in ALS patients.

“Oral levosimendan has potential to make an important contribution to treating patients with ALS in the future and it’s really great that Orion is making this long-term commitment to the patients taking part in that research,” Merit Cudkowicz, MD, director of the Healey Center for ALS at Masachusetts General Hospital and the lead investigator of the REFALS and REFALS-ES studies, said in a press release.

Levosimendan is a calcium sensitizer and potassium channel opener marketed under the name Simdax — the therapy is not yet approved in the U.S. As an intravenous (into-the-vein) therapy, levosimendan is prescribed for the acute worsening of severe chronic heart failure but is also able to sensitize skeletal muscles, such as those responsible for breathing, to calcium.

The ongoing REFALS (NCT03505021) trial is still looking for participants, aiming to recruit a total of 450 ALS patients across 105 sites in the U.S., Canada, European Union, and Australia. Enrollment is anticipated to be open until early summer; more information is available here.

The study’s main objective is to investigate the potential benefits of prolonged treatment with levosimendan on the respiratory muscles in ALS patients. The therapy is expected to help stop the deterioration in patients’ ability to breathe and delay the need for ventilation support.

Specifically, researchers will assess changes in lung function, measured by the supine slow vital capacity — the maximum volume of air that can be slowly inhaled or exhaled when in a supine (lying face up) position — after 12 weeks of treatment. This is important because signs of respiratory insufficiency often appear when lying down.

Additional objectives include changes in the Revised ALS Functional Rating Scale (ALSFRS-R) function, an established method for monitoring disability progression in ALS patients, including respiratory function and survival.

Participants are randomly assigned to receive either levosimendan, administered in 1 mg oral capsules, or a placebo once to twice a day for 48 weeks (11 months).

Results from the Phase 2 LEVALS trial (NCT02487407), which randomized 66 ALS patients to treatment with levosimendan (1 mg and 2 mg daily doses) or a placebo for two weeks separated by a wash-out period (19-23 days), showed that the treatment was well-tolerated. After completing the third treatment period, patients continued to an open-label follow-up part for six months.

The most common adverse events were headaches and an increased heart rate.

While the study failed to show differences in the primary objective — changes in slow vital capacity when sitting at nine months — treatment with levosimendan led to promising signals in supine slow vital capacity.

If the results of both REFALS and REFALS-ES are positive, Orion may plan to file for marketing authorization for oral administration of levosimendan in ALS in the U.S. and Europe. The therapy has been designated an orphan drug in both countries.