HOW DOES A DRUG GET DEVELOPED?

DISCONTINUED: Stages of Development for BMN 290

The drug development process can be thought of as a series of stages, and drugs must successfully pass through each stage to become available to patients. This treatment has been evaluated, and the program has been discontinued. Thus, it is not in the pipeline.

BioMarin

Dr. Joel Gottesfeld at the Scripps Institute and RepliGen worked together to design novel HDAC inhibitors that act at the DNA/gene level and increase frataxin protein production in cells from FA patients and in FA animal models. The Repligen Corporation licensed these HDAC inhibitors from Scripps for the purposes of advancing them through preclinical development and clinical trials in FA. Repligen and Dr. Gottesfeld, with support from FARA, MDA and GoFAR, and with the FA mouse-model investigators, worked to develop an HDAC inhibitor for FA.

April 2013: RepliGen identified a lead candidate (RG2833) and a follow-on candidate (RG3250). RG2833 completed a Phase 1 clinical trial in FA patients in Torino, Italy in April, 2013. This trial was designed to study dose and safety. There were four cohorts of subjects who were given single escalating doses of the drug and monitored with various blood and biophysical tests. In the third and fourth cohorts, which were the highest dose levels, the treatment was well tolerated and there was an increase in frataxin mRNA (a measure of frataxin gene expression).

RG2833 did not continue clinical trials with longer term exposure because metabolites formed from the compound has safety liabilities. RepliGen continued working on follow-on compounds with better access to the central nervous system, better metabolic stability, and that increased frataxin similarly to RG2833.

January 2014: Repligen announced that BioMarin acquired the HDAC inhibitor program. BioMarin continued work to identify a new lead candidate with improved characteristics over RG2833.

BioMarin nominated a new clinical candidate BMN 290.

August 2019: BioMarin announced plans to discontinue preclinical studies in the BMN 290 program for Friedreich’s Ataxia.