Trial Provides Hope for Rare Disease Drug Development

Combinations of drugs already approved found to be safe in treatment of rare disease.

Combinations of drugs already approved found to be safe in treatment of rare disease.

Combinations of previously approved drugs showed promise for the treatment of rare diseases in a recent clinical trial.

In a study published recently in the Orphanet Journal of Rare Diseases, researchers examined the re-use of existing drugs for new purposes to evaluate their potential to save time and resources, while also circumventing the limited funding into rare disease drug development. The potential of combination therapy is based on the hypothesis that diseases can be treated more efficiently through the use of multiple disease-relevant targets.

The researchers hope to find treatment options for the presently incurable Charcot-Marie-Tooth type 1A disease (CMT1A), which is a rare genetic condition affecting approximately 1 in 5000 people.

"Considering the debilitating nature of the disease and the absence of treatment, there remains a pressing unmet need for an efficacious and safe treatment for CMT1A,” lead investigator Shahram Attarian of Marseilles University Hospital in France said in a press release. “The study shows that we now have a potential treatment that is safe to use, but also shows some initial promise in being effective. This invaluable insight will be key in designing the next stages of the international phase 3 clinical trial which is set to begin in 2015."

The trial evaluated the potential of PXT3003, which is a low-dose combination of 3 previously approved well-known compounds for other conditions. Baclofen treats spasticity, naltrexone treats opiate and alcohol addiction, and sorbitol treats intestinal disorders.

The phase 2 randomized clinical trial enrolled 80 adult patients with mild-to-moderate CMT1A. The patient groups received twice-daily placebos or 1 of 3 increasing doses of PXT3003 over 12 months.

PXT3003 was found to be safe and tolerable, with the drug showing no indication of negatively influencing vital signs, electrocardiogram measurements, or blood tests. Treatment-related adverse events were similar across all treatment groups including the placebo cohort, with most of the side effects labeled as mild, transient, and benign.

There were also promising preliminary results for the efficacy of the treatment, including improved measurements of everyday activities, sensory and motor symptoms, and arm and leg strength.

Among patients who took 3 increasing doses, in whom symptoms of the disease evolved since childhood, the highest group exhibited consistent improvement after 12 months. These results suggest benefits for the testing of PXT-3003 in children as a preventative treatment.