Raxone Delays Assisted Ventilation in DMD Patients by 3 Years, Phase 3 Trial Results Show

José Lopes, PhD avatar

by José Lopes, PhD |

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Treatment of Duchenne muscular dystrophy (DMD) patients with Raxone (idebenone) delays the need for assisted ventilation by three years, new data from a Phase 3 clinical trial show.

Trial results also demonstrate that measuring the air flow speed in and out of the lungs, or peak expiratory flow (PEF), predicts respiratory decline in these patients.

Santhera Pharmaceuticals, Raxone’s developer, recently presented the data at the 15th International Congress on Neuromuscular Diseases in Vienna. The company’s presentations at the conference included a symposium where a panel of experts discussed the trial results.

“We are delighted that the expert panel participating at our symposium will present novel data which demonstrate that decline in PEF is a direct indicator of time to initiation of assisted ventilation and risk of death and can serve as a measure for disease progression,” Thomas Meier, PhD, CEO of Santhera, said in a press release before the event.

The DELOS Phase 3 trial (NCT01027884) was a pivotal, double-blind, 52-week study in 64 DMD patients who were not taking steroids. The participants were randomized to receive either 900 mg/day of Raxone or a placebo three times a day.

According to Santhera, the results showed that PEF as percent predicted (PEF%p) is a sensitive and early marker of respiratory decline in DMD patients of different ages.

Moreover, both PEF and forced vital capacity (FVC) — the amount of air exhaled after a deep breath — predict how long it takes for clinically relevant events, such as hospitalization due to respiratory causes, assisted ventilation and death, to occur.

Comparing results of the trial with natural history data, Raxone can be associated with a delay in assisted ventilation by three years.

“As our knowledge of the natural history of respiratory function decline in DMD increases, the understanding of the clinical relevance of different respiratory function measures continues to evolve,” said Oscar H Mayer, MD, a professor of clinical pediatrics at the University of Pennsylvania.

“The most recent work is showing that both PEF and FVC are equally important predictors of time to life-altering events such as assisted ventilation and death,” added Mayer, who is also the medical director of the Pulmonary Function Testing Laboratory at the Children’s Hospital of Philadelphia.

“Today glucocorticoid steroids are recommended standard of care, particularly in young patients with DMD, primarily to maintain upper and lower limb strength,” said Thomas Voit, MD, PhD, one of the investigators in DELOS.

Regarding respiratory function, Voit, who chaired the symposium in Vienna, said data showed that steroids delay the onset of respiratory decline, but not the rate of decline. “Our priority must be to develop therapeutic options that can reduce the rate of respiratory decline in the hope of delaying the time to subsequent life-altering events,” he said.

Santhera is now conducting another Phase 3 trial called SIDEROS (NCT02814019), to assess whether Raxone is able to prevent respiratory decline in DMD patients not using glucocorticoid steroids. It is enrolling an estimated 266 patients at sites across the U.S., Europe and Israel. Results are expected in late 2019.

Raxone is a synthetic analog of ubiquinone, which is believed to play an antioxidant role in cells, while also being involved in the function of mitochondria, which provide energy to cells.

According to Meier, the new data are “highly relevant” for Raxone’s marketing authorization applications in the U.S and Europe, which the company is currently preparing to submit.

Recently, the U.K.’s Medicines and Healthcare products Regulatory Agency renewed its Early Access to Medicines Scheme (EAMS) with Santhera, extending access to Raxone for DMD patients in the U.K.

In the U.S., the medication is available to eligible DMD patients through Santhera’s expanded access program.

In January 2018, the European Medicines Agency issued a second negative recommendation against extending Raxone for the treatment of DMD, beyond its approval in Europe for Leber’s hereditary optic neuropathy. The agency released its first negative opinion in September 2017, based on doubts that the DELOS results provided enough evidence of Raxone’s effectiveness.