Raxone (Idebenone) Shows Promise as DMD Therapy in SYROS Trial

Long-term treatment with Raxone (idebenone) slows down loss of respiratory function in Duchenne muscular dystrophy (DMD) patients for up to six years, according to recent results from Santhera Pharmaceuticals’ SYROS trial.

The company is recruiting participants for the SIDEROS-E Phase 3 study (NCT03603288). It aims to assess the long-term safety and efficacy of Raxone in DMD patients who completed the SIDEROS study (NCT02814019).

The study’s findings will be presented at the April 13-17 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in Orlando, Florida. Researchers are also planning to publish their results in a peer-reviewed journal.

Currently under investigation for the treatment of DMD, Raxone is a synthetic analog of ubiquinone, a key antioxidant that also plays a role in the cellular production of energy.

The chemical compound increases energy output of mitochondria (cells’ powerhouse) by carrying and dropping off negatively charged particles (electrons) within mitochondria, which use them to generate energy. Its antioxidant properties mean that the compound helps fight off harmful free radical molecules.

Ultimately, the investigational drug allows muscle cells to maintain their cellular energy supply, which has been compromised by disease-specific lack of dystrophin.

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In 2015, Santhera designed a double-blind, randomized, placebo-controlled Phase 3 trial called DELOS (NCT01027884). A total of 64 patients (ages 10–18) were randomly assigned to receive either Raxone (900 mg/day) or placebo three times a day with meals for 52 weeks. Results demonstrated that Raxone reduced the loss of respiratory function, delaying the need for  assisted ventilation by three years.

In the SYROS trial, investigators collected long-term, retrospective real-world data from the 18 patients who completed the DELOS study and continued Raxone treatment (same dose) for about 4.2 years (range 2.4–6.1 years).

Patients were able to use the investigational therapy because of an Expanded Access Program (EAP), also known as “compassionate use,” which provides a pathway for subjects to access pre-approval drugs, biologics, and medical devices used to diagnose, monitor, or treat patients with serious diseases for which there are no comparable or satisfactory therapy options available outside clinical trials.

In the U.S., the therapy is available through the U.S. Food and Drug Administration-authorized EAP BreatheDMD. 

SYROS assessed patients’ respiratory function for up to six years and compared it to when the patients were not on Raxone (before the DELOS study).

In line with DELOS’ findings, SYROS shows that Raxone reduces respiratory function decline by 50 percent, considering the predicted forced vital capacity of each patient.

Forced vital capacity refers to the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible; doctors can predict a normal value for it based on a patient’s age, height, race, and gender.

Importantly, Raxone’s beneficial effect was maintained for up to six years. The therapy was also associated with a lower rate of lung-related adverse events and hospital admissions.

Inspiratory and expiratory respiratory function was conserved for a longer period while on Raxone, compared to patients’ clinical status before DELOS.

“We are very excited to see that the significant treatment effect with idebenone observed in our 52- week Phase 3 DELOS study is maintained over the long term,” Kristina Sjöblom Nygren, MD, chief medical officer and head of development at Santhera, said in a news release.

“The new findings are highly relevant for DMD patients in respiratory decline who have an urgent need for a therapy to modify the declining course of respiratory function decline and ultimately delay the need for assisted ventilation.”