Interferon gamma (Actimmune®)
Interferon gamma (Actimmune) is a drug that is approved for treatment of other rare diseases – chronic granulomatous disease (CGD) and severe, malignant osteopetrosis. It was identified as potential therapeutic for the treatment of FA because of data in model systems showing that it upregulated frataxin expression in vitro and in vivo.
DISCONTINUED: Stages of Development for Interferon gamma (Actimmune®)
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.
Interferon gamma (IFN-γ) increased frataxin mRNA and protein levels in patient cells. Treatment with interferon gamma also increased frataxin protein in dorsal root ganglia (DRG) neurons from the YG8R FRDA mouse model. Mice treated with IFN-γ demonstrated enhancements of locomotor activity, improvements in motor coordination and prevention of DRG degeneration.
Early 2013: Roberto Testi carried out a pilot study of interferon gamma in FA patients. This study evaluated the safety and tolerability of multiple doses of interferon gamma in individuals with FA and changes in frataxin levels.
Late 2013: Dr. David Lynch ran an open-label study of IFNg in late 2013. This study evaluated safety, tolerability, and efficacy in children with FA. FARA funded this study and Vidara Pharmaceuticals generously donated study drug.
In the Lynch study, there were small non-significant change in frataxin levels that varied between tissues.
The clinical data obtained from the study which showed a significant improvement in neurological function measured by the Friedreich Ataxia Rating Scale (FARS). No statistically significant relationships were observed between frataxin protein levels, FARS scores, and in vivo IFN-γ levels. In addition, this study did not have a control or placebo group as it was a short, open label pilot study.
April 2015: Horizon Pharma announced that they were granted Fast Track Designation from the FDA for ACTIMMUNE® (interferon gamma-1b) in the treatment of Friedreich’s ataxia.
June 2015: Horizon announced the initiation of a Phase III Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich’s Ataxia study (“STEADFAST”) of ACTIMMUNE (interferon gamma-1b) for the treatment of people with Friedreich’s Ataxia. This study enrolled individuals with FA, ages 10-25 years.
No differences were noted between the groups after 6 months of treatment in the mFARS or secondary outcome measures. No change was noted in buccal cell or whole blood frataxin levels. However, during an open‐label extension period, subjects had a more stable course than expected based on natural history data.
This study provides no direct evidence for a beneficial effect of IFN‐γ1b in FA. The modest stabilization compared to natural history data leaves open the possibility that longer studies may demonstrate benefit.