Interferon gamma

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Compound Name:Interferon gamma-1bMolecular Target:Type II interferon receptorsMolecular Structure:recombinant, humanLicensed Indication:chronic granulomatous disease; severe, malignant osteopetrosisManufacturer and/or Distributor:InterMuneInitial FDA Approval:1999Summary:Interferon gamma-1b (Actimmune) is a recombinant human Type II interferon produced in E. coli. Type II interferon binds to specific receptors found on all cell types. Type II interferon can thus have a wide variety of potential physiological effects that are anti-viral, anti-bacterial, anti-apoptotic, anti-tumor, and immunomodulatory. Interferon gamma-1b is administered by subcutaneous injection three times a week. Interferon gamma-1b was first FDA approved in 1999 for treatment of chronic granulomatous disease (CGD). An indication for severe, malignant, osteopetrosis was added in 2000. October 2014, the FDA has granted orphan drug status to Actimmune for the treatment of Friedreich’s Ataxia (FA). In CGD interferon gamma-1b leads to a substantial reduction in the frequency of serious infections. In April 2015, Actimmune was granted Fast Track status for FA by the FDA. In osteopetrosis, it delays disease progression, as indicated by decreased bone density, decreased infections, and increased hemoglobin levels. The mechanisms of the clinical benefits in both conditions have not been established. The National Cancer Comprehensive Network recommends use of Actimmune in mycosis fungoides and Sézary syndrome. Two randomized clinical trials assessing the results of interferon gamma-1b treatment in idiopathic pulmonary fibrosis showed no statistically significant differences in the clinical endpoint of overall survival between interferon gamma-1b and placebo. Safety concerns include hypersensitivity, neurologic and cardiac disorders, cytopenias, and hepatic toxicity. Reversible neutropenia and thrombocytopenia have also been observed during Actimmune therapy.References

Package Insert: http://www.actimmune.com/pdf/ACTIMMUNE_PI_Effective_US%207-16.pdf

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5. The NCCN Drugs and Biologics Compendium (NCCN Compendium^TM) http://www.nccn.org/professionals/drug_compendium/content/contents.asp

6. Richeldi L. Clinical trials of investigational agents for IPF: a review of a Coshrane report. Respir Res. 2013;14 Suppl 1:S4. http://www.ncbi.nlm.nih.gov/pubmed/23734867

7. Seyer L, Greeley N, Foerster D, Strawser C, Gelbard S et al. Open-label pilot study of interferon gamma-1b in Friedreich ataxia. Acta Neurol Scand. 2014 Oct 21. http://www.ncbi.nlm.nih.gov/pubmed/25335475

8. Yiu EM, Tai G, Peverill RE, Lee KJ et al. An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels. J Neurol. 2015. 262(5):1344-1353. http://www.ncbi.nlm.nih.gov/pubmed/25845763

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