WALTHAM, Mass.--(BUSINESS WIRE)--
Repligen Corporation (NASDAQ:RGEN - News) announced today that it has enrolled its first patient in a Phase 1 clinical trial of RG2833 in adult patients with Friedreichs ataxia (FA). FA is an inherited neurodegenerative disease caused by low levels of the protein frataxin which results in symptoms that typically present in childhood and lead to progressive loss of muscle and nerve function, often resulting in loss of life by early adulthood. RG2833 is an orally bioavailable, class 1 histone deacetylase inhibitor (HDACi) specifically designed to increase frataxin production in patients with FA. This study is being conducted in Turin, Italy and is the first clinical trial of a drug that targets the core genetic defect in FA.
The Phase 1 trial is a single ascending dose, crossover study in up to 20 adult FA patients. It is designed to evaluate the pharmacokinetic and safety profile of RG2833. Importantly, this study will also evaluate the pharmacodynamic response of RG2833 on various cellular and molecular biomarkers, including frataxin mRNA and frataxin protein.
This Phase 1 trial in patients will generate valuable information on the safety and pharmacology of RG2833, said Walter C. Herlihy, Ph.D., President and Chief Executive Officer of Repligen. In addition, this study has the potential to provide early evidence of clinical activity for RG2833 in the treatment of Friedreichs ataxia.
RG2833 is an attractive drug candidate, given its oral bioavailability and potential to target and activate the defective gene responsible for Friedreichs ataxia, said lead investigator Luca Durelli, M.D., Chief of Neurology at San Luigi Gonzaga University Hospital in Turin, Italy and lead investigator for the Phase 1 trial. The effects of FA are devastating for our young patients and their families. I am happy to be involved with the study and to help address the critical need for a therapy that has the potential to slow disease progression.
Friedreich's ataxia is caused by a single gene defect that results in inadequate production of the frataxin protein. Low levels of frataxin impair the function of nerves coordinating muscle movements in the arms and legs and the nerve tissue in the spinal cord and can lead to a life-shortening cardiomyopathy. RG2833 is a Class 1 HDAC inhibitor that has been designed to upregulate the frataxin gene and has been shown in preclinical studies in animal models and patients cells to increase production of this key protein. These results indicate that RG2833 may increase frataxin production in patients and has the potential to be an important treatment for Friedreichs ataxia.
Friedreichs ataxia disease biology provides evidence that a small increase in expression of the defective gene could potentially slow disease progression, said James R. Rusche, Ph.D., Senior Vice President, Research and Development at Repligen. RG2833 is the first compound that targets activation of this defective gene. If our unique approach of using small molecules for protein replacement is successful, it has the potential to significantly improve outcomes for patients with FA. We are hopeful that the Phase 1 trial will elucidate the role for HDAC inhibition in FA, and inform future efficacy studies.
RG2833 is a new chemical entity that is the subject of a composition of matter patent and will remain in force until 2029 prior to any patent term extensions. Portions of this clinical trial are supported by a grant from the Italy based patient advocacy group GoFAR. Repligens additional research efforts in FA have been partially funded with grants from the Friedreichs Ataxia Research Alliance (FARA), GoFAR, the Muscular Dystrophy Association, the European Friedreichs Ataxia Consortium for Translations Studies (EFACTS) and the National Ataxia Foundation (NAF). RG2833 has been developed in collaboration with scientists from The Scripps Research Institute and a broad international network of scientific thought leaders. Repligen is also evaluating other HDAC inhibitors in animal models of Huntingtons disease and cognition.
Orphan Drug Designations
Repligen has previously received U.S. Orphan Drug and European Orphan Medicinal Product designations for RG2833 for the treatment of Friedreichs ataxia. Both orphan programs provide incentives for the research, development and marketing of products intended to diagnose, prevent or treat rare conditions and/or serious or debilitating diseases with unmet medical needs. Orphan designation grants the sponsor exclusive marketing rights for seven years in the U.S. and ten years in the EU following regulatory approval of the designated product.
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Repligen Initiates Phase 1 Clinical Trial of RG2833 in Patients with Friedreich’s Ataxia