The FDA has granted orphan drug status to pegylated interferon lambda 1a (Lambda, Eiger Bio, Inc.) as a potential treatment for chronic hepatitis delta virus (HDV) infection.
Hepatitis delta is caused by infection with HDV and is considered to be one of the most severe forms of viral hepatitis in humans. Hepatitis delta occurs only as a coinfection in individuals harboring hepatitis B virus (HBV). Hepatitis delta leads to more severe liver disease than HBV alone and is associated with accelerated liver fibrosis, liver cancer, and liver failure. Hepatitis delta is a disease with a significant impact on global health; it may affect as many as 15–20 million people worldwide. The prevalence of HDV varies among different parts of the world. Globally, HDV infection is reported to be present in approximately 4.3% to 5.7% of chronic hepatitis B carriers. The prevalence of HDV in patients infected with chronic HBV is even higher in certain regions, including parts of Mongolia, China, Russia, Central Asia, Pakistan, Turkey, Africa, the Middle East, and South America, with an HDV prevalence as high as 60% being reported in HBV-infected patients in Mongolia and Pakistan.
Pegylated interferon lambda 1a is a late-stage, first-in-class, type III interferon (IFN) that stimulates immune responses critical for the development of host protection during viral infections. Pegylated interferon lambda 1a targets type III IFN receptors, which are distinct from the type I IFN receptors targeted by IFN alfa. These type III receptors are highly expressed on hepatocytes with limited expression on hematopoietic and central nervous system cells, which may reduce off-target effects and improve tolerability of pegylated interferon lambda 1a. Although it does not use the IFN alfa receptor, signaling through either the IFN lambda or IFN alfa receptor complexes results in the activation of the same Jak-STAT signal transduction cascade.
Eiger licensed worldwide rights to Lambda from Bristol-Myers Squibb in April 2016. Pegylated interferon lambda 1a has been administered in HBV and hepatitis C virus clinical trials involving more than 3,000 patients, but has not yet been approved for any indication.
Source: Eiger; September 5, 2017.