The biopharmaceutical company Repligen Corp., headquartered in Waltham, Mass., has launched a phase 1 clinical trial to test its experimental compound, RG2833, in adults with Friedreich's ataxia (FA). The trial is the first of a therapy specifically developed to treat the underlying molecular cause of FA.
The phase 1 trial is being conducted at San Luigi Gonzaga University Hospital in Turin, Italy, and will test the safety of the drug.
Favorable results from the trial could pave the way for later-stage trials both in Europe and the United States — a necessary step in obtaining U.S. Food and Drug Administration (FDA) approval of RG2833 for the treatment of FA.
Repligen expects to enroll approximately 20 adults with FA in the trial. Each will receive a single dose of RG2833. (A range of doses will be tested.) The trial is double-blinded, meaning neither the investigators nor trial participants will know what dose each participant receives.
The main focus of the trial is to establish the safety and tolerability of RG2833 in people with FA. However, investigators also will evaluate the drug's pharmacokinetics profile (the ways in which the body works on the drug) and its pharmacodynamics (the effects the drug has on the body).
The underlying cause of FA is a defect in the frataxin gene that causes it to be abnormally "turned off," leading to a deficiency of the frataxin protein. It's long been thought that increasing frataxin levels, or finding ways to replicate the functions normally performed by the missing protein, potentially may serve as effective therapeutic strategies in FA. (For more about the causes of FA, read FA: A Case of Impaired Ironworks, Quest, January-March 2011.)
RG2833 belongs to a class of drugs called histone deacetylase (HDAC) inhibitors. The compound is thought to work by "turning back on" the frataxin gene, allowing cellular machinery to read its genetic instructions and produce the needed frataxin protein.
Previous studies in mice with a disease resembling FA have confirmed that RG2833 is most potent against the enzyme HDAC3, and that blocking or inhibiting that enzyme increases frataxin production.
The FDA has granted RG2833 orphan drug designation, which may qualify Repligen to receive seven years of market exclusivity in the United States, providing it is the first company to receive FDA approval of RG2833 for treating FA.
The phase 1 Italian trial is expected to assess the safety of RG2833 use in humans, and help researchers design later-stage trials to test its efficacy as a therapeutic strategy in FA.
"MDA is pleased to see that its early investment in Repligen's efforts to develop RG2833 as a therapy for FA has helped propel the experimental therapy to the stage where it's now ready to be tested in humans," said MDA Vice President of Research Sanjay Bidichandani.
"This trial is a solid step forward in the development of a therapy for FA and represents a promising advance for people with FA worldwide."
MDA has awarded Repligen two grants to fund development of RG2833 for FA. The first, awarded in late 2007, totaled nearly $1 million. In December 2009, MDA awarded Repligen a supplemental grant of $731,534 to support ongoing development and completion of the preclinical testing required to advance the experimental drug toward human clinical trials. The awards were made through MDA Venture Philanthropy, the drug development arm of MDA's translational research program.
In addition to MDA support, Repligen's development of RG2833 has been supported by the Scripps Research Institute in La Jolla, Calif.; the Friedreich's Ataxia Research Alliance (FARA), headquartered in Springfield, Va.; and the National Ataxia Foundation, based in Minneapolis, Minn.