Biopharmaceutical company Raptor Pharmaceutical Corp. has submitted an investigational new drug application (IND) to the US Food and Drug Administration (FDA) for the clinical development of RP103 as a potential treatment for Leigh syndrome and other mitochondrial disorders. RP103 is currently marketed in the US as Procysbi (cysteamine bitartrate) delayed-release capsules for the management of nephropathic cystinosis in adults and children 6 years and older.

"Leigh syndrome is one of the most devastating of mitochondrial disorders and the RP103-MITO-001 trial will explore a new mechanism of action against this deadly illness," said the trial's lead investigator, Bruce H Cohen, MD, Professor of Paediatrics and Director of Neurology at Akron Children's Hospital. "RP103 may stimulate steady and continuous depletion of reactive oxygen species which are toxic to cellular function and structure. These reactive oxygen species are abnormally high in patients with Leigh syndrome."

The RP103-MITO-001 trial is designed to evaluate the safety, tolerability and efficacy of RP103 in patients with genetically confirmed Leigh syndrome and other mitochondrial disorders. The clinical plan includes an open label, 24 week, phase IIb study in 32 patients (up to a maximum of 64 patients). Patients with Leigh syndrome are expected to comprise two-thirds of the enrolled population in the study. Initiation of the clinical trial is planned for the first quarter of 2014 at four clinical sites in the US. Based on an adaptive design statistical plan, Raptor will conduct two interim analyses, after 12 patients and then 24 patients have completed the study to determine final sample size. The primary endpoint of the study will be the change from baseline in the Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) at 24 weeks. Secondary endpoints will include observations of myopathy, dystonia, seizures, motor development, dyskinesia, quality of life, and activities of daily living. Interim results from the initial 24 patients are expected by the end of 2014.

In addition to providing an antioxidant activity directly, RP103 is believed to increase mitochondrial glutathione which acts as a scavenging agent of reactive oxygen species. Reactive oxygen species are a byproduct of mitochondrial energy production and place oxidative stress on cells. In patients with mitochondrial dysfunction, these reactive oxygen species are produced at dangerously high levels. By increasing levels of the antioxidant glutathione in the mitochondria, RP103 may reduce the toxic oxidative stress typically associated with mitochondrial disorders.

"RP103 is already approved, both in the US and in the EU, for the treatment of another deadly illness, nephropathic cystinosis," said Patrice Rioux, MD, Ph.D., Raptor's chief medical officer. "Our extensive understanding of the mechanisms of action of RP103 coupled with its potential tolerability, pharmacokinetics and pharmacodynamics is generating substantial rationale to conduct further studies in other orphan diseases. In addition to mitochondrial disorders including Leigh syndrome, we are already conducting clinical trials of RP103 in NAFLD and Huntington's disease, and we will consider additional indications as the science emerges."

Leigh syndrome is a severe neurological disorder caused by genetic defects in mitochondrial or nuclear DNA affecting respiratory chain function that typically results in death within the first decade of life. The condition causes increased production of reactive oxygen species which disrupts mitochondrial electron transport and affects cellular function in a variety of tissues. Typically observed during the first year of life, Leigh syndrome is characterized by a failure to thrive, lack of coordination, involuntary and sustained muscle contraction, muscle wasting, and multiple organ failure.

Raptor Pharmaceutical Corp. is a biopharmaceutical company focused on developing and commercializing life-altering therapeutics that treat rare, debilitating and often fatal diseases.