Pegylated interferon lambda 1a (also called IL-29) has fewer side-effects compared to its close cousin pegylated interferon alfa, besides higher level activity against hepatitis C virus infection, said developers of the drug Bristol-Myers Squibb and ZymoGenetics.
Pegylated interferon lambda 1a, when administered once-weekly or once every 2 weeks with or without daily ribavirin, demonstrated potent activity against hepatitis C virus (HCV) in genotype 1 patients.
Compared with pegylated interferon alfa, however, interferon lambda caused fewer flu-like and hematological (blood-related) side effects.
Interferon lambda 1a is a member of the type 3/lambda interferon family, which binds to a receptor with a more restricted distribution than the receptor for interferon alfa/type 1 interferons, and therefore potentially has a more favorable toxicity profile.
Interferon lambda is generated by the immune system in response to viral infection. IL-29 is a member of the type 3 Interferon family, which includes IL-28A and IL-28B, and signals through the same receptor as IL-28A and IL-28B.
Like pegylated interferon alfa (Pegasys or PegIntron) — the approved standard therapy for hepatitis C — pegylated interferon lambda 1a (or PEG-interferon lambda) is formulated to last longer in the body than non-pegylated forms.
In a Phase 1b study presented at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, Bristol-Myers Squibb Company and ZymoGenetics, Inc. included data on 56 patients in the study.
The Phase 1b clinical trial was designed to evaluate the safety and antiviral activity of PEG-Interferon lambda when given as a single agent or in combination with ribavirin in genotype 1 HCV patients with relapsed disease and in treatment-naive patients.
Interferon lambda 1a showed antiviral activity at all dose levels tested.
“We are pursuing this investigational pathway to address the fact that although current interferons have been the backbone of therapy with meaningful efficacy, they are often poorly tolerated, leading to dose reductions, poor compliance and avoidance of treatment,”
stated Brian Daniels, MD, senior vice president, Global Development & Medical Affairs, Bristol-Myers Squibb.
A majority of patients across all PEG-Interferon lambda treatment arms achieved a greater than 2 log reduction in HCV RNA.
Of the patients in the single agent arm of the study, all 12 of those patients receiving 1.5 mcg/kg and 3.0 mcg/kg weekly for four weeks achieved a greater than 2 log decrease in HCV RNA. Five of the 12 patients receiving 1.5 mcg/kg and 3.00 mcg/kg every two weeks for four weeks achieved a greater than 2 log decrease in HCV RNA.
At PEG-Interferon lambda doses of 0.75 mcg/kg, 1.5 mcg/kg and 2.25 mcg/kg administered in combination with ribavirin in treatment-relapsed patients (n=18), a greater than 3 log mean maximum decrease in viral load was observed. Of those patients, eleven (61%) had less than 1,000 HCV RNA copies at Day 29.
Treatment-naive patients, who were treated with 1.5 mcg/kg of PEG-Interferon lambda in combination with ribavirin (n=7), also had a greater than 3 log mean maximum decrease in viral load and two patients (29%) achieved a rapid virologic response (RVR), or undetectable HCV RNA copies, at 4 weeks.
The most common adverse events were fatigue (29%) and nausea (13%). There were minimal effects on neutrophil counts. Minimal constitutional symptoms or hematologic effects were observed with PEG-Interferon lambda given as a single agent or in combination with ribavirin.
Interferon lambda (IL-29) is a type 3 interferon that binds to a unique receptor with more restricted distribution than the receptors targeted by type 1 interferons, such as interferon alpha. It is in development for hepatitis C.
Bristol-Myers Squibb is a global biopharmaceutical company.
ZymoGenetics markets Recothrom Thrombin, topical (Recombinant), a synthetic version of a human blood-clotting enzyme used to stop bleeding during surgery. Interleukin-21 is a novel cytokine in clinical development for the treatment of metastatic melanoma and renal cell carcinoma. Several other proprietary product candidates are in preclinical development. In addition, ZymoGenetics has licensed rights to multiple clinical and preclinical drug candidates being developed by other companies.