Date: 2016-10-16
Type of information: Recruitment of the first patient
phase: 3
Announcement: recruitment of the first patient
Company: Santhera Pharmaceuticals (Switzerland)
Product: Raxone®
Action
mechanism: benzoquinone analog/quinone. Raxone® (idebenone), a synthetic short-chain benzoquinone and a cofactor for the enzyme NAD(P)H:quinone oxidoreductase (NQO1), is capable of transferring electrons directly onto complex III of the mitochondrial electron transport chain, thereby circumventing the complex I defect and restoring cellular energy levels in retinal ganglion cells and promoting recovery of visual acuity. Nerve and muscle cells, including heart muscle cells, are particularly energy-demanding and are, therefore, more prone to rapid cell damage or death due to mitochondrial dysfunction. Through preserving mitochondrial function and protecting cells from oxidative stress, it is believed that Raxone®/Catena® can prevent cell damage and increase the production of energy within impaired nerve and muscle tissue in Friedreich's Ataxia and Duchenne patients. Idebenone has been granted orphan drug designation for DMD in Europe and the US and has use patent protection until 2026 in Europe and 2027 in the US. The FDA recently granted Fast Track designation for Raxone®(idebenone) for the treatment of DMD.
Disease: Duchenne muscular dystrophy (DMD)
Therapeutic area: Rare diseases - Genetic diseases - Neuromuscular diseases
Country: Austria, Belgium, France, Germany, Italy, Netherlands, Spain, Sweden, Switzerland, UK, USA
Trial
details: SIDEROS is a phase III, double-blind, randomized, placebo-controlled trial with Raxone in approximately 260 DMD patients receiving concomitant glucocorticoids. Patients with declining respiratory function on any stable glucocorticoid treatment scheme and irrespective of the underlying dystrophin mutation or ambulatory status will be eligible. Study participants will receive either Raxone (900 mg/day; given as 2 tablets 3 times a day with meals) or placebo for 78 weeks (18 months). The primary endpoint of the trial is change from baseline to week 78 in forced vital capacity % predicted (FVC%p). Secondary endpoints include changes from baseline in % predicted peak expiratory flow (PEF%p), time to first 10% decline in FVC and change from baseline in inspiratory flow reserve. Patients completing the trial will be offered the opportunity to enroll in an open label extension study where all patients receive Raxone. The study will be conducted at about 50 centers in the United States and Europe. (NCT02814019)
Latest
news: * On September 28, 2016, Santhera Pharmaceuticals announced that the first patient has been enrolled at the University of Kansas Medical Center (KUMC), Department of Neurology, Kansas (USA) in Santhera's randomized, double-blind, placebo-controlled phase III (SIDEROS) trial. The trial will assess the efficacy of Raxone® in slowing the rate of respiratory function decline in Duchenne muscular dystrophy (DMD) patients receiving concomitant glucocorticoids.
"We first observed the efficacy of Raxone in slowing the rate of respiratory function decline in DMD patients in both glucocorticoid-using and non-using patients in the phase II DELPHI study," commented Thomas Meier, PhD, CEO of Santhera. "The successful Phase III DELOS trial which enrolled glucocorticoid non-using patients then confirmed a clinically relevant and statistically significant benefit of Raxone® treatment on pulmonary function. The now initiated Phase III SIDEROS trial is designed to confirm the efficacy of Raxone® in patients experiencing respiratory function decline that are currently taking glucocorticoids. If successful, this study will provide data that support use of Raxone® in all DMD patients experiencing respiratory decline irrespective of their glucocorticoid use. The high level of interest from investigators and the patient community should allow us to recruit this study quickly."
The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) is currently assessing a Marketing Authorization Application (MAA) for Raxone® in DMD patients with respiratory function decline who are not taking concomitant glucocorticoids. The indication would include patients who previously were treated with glucocorticoids or in whom glucocorticoid treatment is not desired, not tolerated or is contraindicated. The MAA was submitted as a Type II variation of the company's existing marketing authorization for Raxone® for the treatment of visual impairment in patients with Leber's hereditary optic neuropathy (LHON).
