An exploratory Phase 1/2 clinical trial in primary progressive multiple sclerosis (PPMS) conducted at the National Institutes of Health (NIH) confirms the safety profile of Raxone (idebenone) at a dose of 2,250 mg daily over two years.
But no difference in effectiveness was found between the Raxone-treated group and the placebo group.
The announcement was made by Santhera Pharmaceuticals, the company developing Raxone.
The trial (NCT00950248) is a double-blind, placebo-controlled study assessing the safety and efficacy of Raxone in PPMS. It is sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH.
The initial aim was to assess the safety, effectiveness, and mechanism of action of Raxone in 85 patients with PPMS over two years. A total of 77 patients were eventually randomized, and 66 completed the trial (33 in the active group and 33 in the placebo group).
The entire trial period combined a one-year observational pre-treatment phase and a two-year treatment period.
There was no difference between Raxone and placebo groups in the occurrence and severity of adverse events.
The study’s primary outcome was to explore the efficacy of Raxone through change in the CombiWISE scale — a disability rating system developed by NINDS investigators.
Combined analysis of CombiWISE data and other clinical assessments and biomarkers indicated that there was no difference between treatment groups on measures of disease progression.
“The long-term study in patients with PPMS confirms the favorable safety profile of idebenone given at higher dose than the currently approved dose for Raxone in Leber’s hereditary optic neuropathy (LHON),” Thomas Meier, chief executive officer of Santhera, said in a press release.
“We thank the NIH team for conducting this long-term pilot study which will add to the knowledge of disease progression and data collection instruments. Clearly, the small sample size is a limitation when studying a therapeutic intervention in such a complex, relentlessly progressing neurological disease.”
In patients with LHON, Raxone (administered at a dose of 900 mg/day) was found to be well-tolerated. The most common side effects were common cold cough, mild-to-moderate diarrhea, and back pain.
The 66 PPMS patients who completed the Phase 1/2 trial will be invited to participate in an open-label extension study (NCT01854359), in which they’ll receive an additional year of treatment with Raxone.
The Phase 1/2 trial is expected to be completed in August 2018 and the extension study a year later, in August 2019.
There is evidence suggesting that oxidative stress may contribute to the damage in PPMS. When energy is produced in mitochondria (the cells’ powerhouses), reactive oxygen species can be produced, causing oxidative stress and leading to cell death.
Raxone is a man-made equivalent of the naturally occurring antioxidant coenzyme Q10. Antioxidants can reduce the level of free reactive oxygen species. This can be particularly helpful to PPMS patients, who studies have shown have significantly lower levels of naturally occurring antioxidants, thus contributing to progression of disease.
Santhera is evaluating whether Raxone can protect the brain and spinal cord from damage that leads to worsening disability in PPMS. Results so far are in line with preclinical-trial studies in mouse models of MS showing that the compound seems to have no effect in preventing or delaying disease symptoms.