About Pegylated-Interferon-Lambda

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About Pegylated-Interferon-Lambda 2017-02-05T20:39:17+00:00

Pegylated-interferon-lambda (PEG-IFN-λ) is a well-characterized, late-stage, first in class, type III interferon that stimulates cell-mediated immune responses that are critical for the development of host protection during viral infections.  IFN-λ targets type III IFN receptors which are distinct from the type I IFN receptors targeted by IFN-α.  These type III receptors are highly expressed on hepatocytes with limited expression on hematopoietic and central nervous system cells, which may reduce the off-target effects associated with other interferons and improve the tolerability of PEG-IFN-λ.  Although IFN-λ does not use the IFN-a receptor complex for signaling, signaling through either the IFN-λ or IFN-a receptor complexes results in the activation of the same Jak-STAT signal transduction cascade.1

Potential Impact of Limited Lambda Receptor Distribution

IFN-λ and IFN-a Signals Through Same Downstream Signaling Pathway2

Eiger is studying PEG-IFN-λ as an investigational therapy for hepatitis delta virus (HDV) infection.  PEG-IFN-λ has been administered in phase 1, 2 and phase 3 in healthy volunteers, HCV and HBV clinical trials involving over 3,000 subjects.  PEG-IFN-λ has not been approved for any indication.  Eiger plans to evaluate PEG-IFN-λ as a potential monotherapy and combination treatment for chronic HDV infection in the second half of 2016.

Clinical Data for PEG-IFN-λ Suggests an Improved Tolerability Profile Relative to PEG-IFN-α.

PEG-IFN-λ and PEG-IFN-α has been evaluated in a Phase 2 clinical study in 163 individuals infected with hepatitis B virus (HBV).3  PEG-IFN-λ treatment resulted in lower rates of headache, flu-like symptoms, and neutropenia compared to PEG-IFN-α.

Flu-like symptoms and neutropenia, occurred less frequently in 16.3% and 2.5% of patients treated with PEG-IFN-λ, compared to 54.2% and 20.7% of patients in the PEG-IFN-α group.  Grade 3-4 increases in transaminases occurred more frequently in patients treated with PEG-IFN-λ (33.8 – 41.3%) compared to patients treated with PEG-IFN-α (18.3 – 23.2%).  In total, 15.0% of patients treated with PEG-IFN-λ required dose reductions compared to a rate of 27.7% with PEG-IFN-α.  These results suggest a promising and potentially better tolerated interferon therapy for HDV.

PEG-IFN- λ Lambda Suppresses HDV RNA in Human Liver-Chimeric Mice

The antiviral effect of PEG-IFN-λ on HDV was demonstrated in human liver-chimeric uPA/SCID mice.  Chronic HBV/HDV co-infected mice were treated with PEG-IFN-λ for 4 weeks.  PEG-IFN-λ decreased HDV-RNA by 1.5-logs as determined by qRT-PCR.4

  1. Donnelly R et al, J Interferon Cytokine Res, 2010, 30(8): 555.
  2. Miller et al, Cytokine Therapies, Ann NY Acad Sci, 2009, 1182: 69.
  3. Chan et al, J Hepatology, 2016, 64: 1011.
  4. Giersch et al, EASL 2013 Monothematic Conference, Poster.

Hepatitis Delta (HDV)

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