DISCONTINUED: Stages of Development for Etravirine

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.

Link to Study

  • Roberto Testi and his team at the University of Rome and the company Fratagene reported results of a drug screening study. They developed a cell-based assay to conduct a high-throughput screening of 853 FDA-approved drugs in search of drugs that could increase frataxin protein levels in the assay. Among the potentially interesting drugs identified as apparently able to increase frataxin protein levels in the cell-based assay, the team focused on etravirine for the next step.
  • The team then introduced the drug to some fibroblasts (skin cells) and lymphoblasts (blood cells) derived from FA patients. In those cells, etravirine seemed able to increase frataxin protein levels to some extent and restore activity of an iron-sulfur-cluster-containing enzyme, aconitase, that is decreased with frataxin deficiency.
  • Etravirine also appeared able to protect FA patient-derived cells from oxidative stress. Initial studies to clarify the mechanism of action indicated that etravirine might be able to increase the translation of frataxin messenger RNA (mRNA) into frataxin protein.

  • Andrea Martinuzzi at the IRCCS Eugenio Medea conducted a Phase II trial of etravirine in individuals with FA. This was an open-label, phase II clinical trial aimed at assessing the safety and efficacy of etravirine in FA. Two doses of etravirine were evaluated over 4 months. The primary efficacy endpoint was changes in peak VO2 as measured by incremental cycle ergometer exercise test. Secondary endpoints included maximal workload, SARA score, cardiac measures, frataxin protein levels in peripheral blood mononuclear cells and molecular analysis of frataxin mRNA translation efficiency.
  • No results of the trial have been posted.