Positive Results From Peregrine Pharmaceuticals' Bavituximab Phase l HCV Trial Presented at AASLD Meeting
The multiple dose, open label study was designed to assess the safety andpharmacokinetic properties of ascending dose levels of bavituximabadministered as monotherapy in patients with chronic HCV infection. Otherstudy objectives included evaluation of anti-viral activity as measured bychanges in serum HCV virus levels and an exploratory analysis of changes inserum cytokine levels as a measure of bavituximab's ability to stimulatecertain components of the immune system.
Results indicate that bavituximab was generally safe and well tolerated,with no dose limiting toxicities or serious adverse events reported.Anti-viral activity (decline of greater than or equal to 0.5 log10 reductionin HCV RNA) was observed at all dose levels and was most consistent inpatients receiving 3 mg/kg of bavituximab. In this cohort, 83% of thepatients demonstrated anti-viral activity. An assessment of the cytokineprofile in this cohort also suggests bavituximab induces a pro-inflammatorycytokine profile, defined as an increase in the ratio of TNF alpha and TGFbeta. Stimulating an immune response is a key proposed anti-viral mechanismof action of bavituximab.
"Meeting all of the objectives of this Phase l trial was an importantmilestone for the bavituximab HCV program," said Steven W. King, president andCEO of Peregrine. "We are particularly pleased with bavituximab's positivesafety profile at all doses tested, its predictable and consistentpharmacokinetic characteristics, and the signs of anti-viral activity andimmune system stimulation that were observed. Based on these results, we havebeen able to identify a target dose range of 3 mg/kg for future clinicalstudies."
Twenty-four patients received bavituximab twice weekly for two weeks atescalating dose levels of 0.3, 1, 3, or 6 mg/kg of body weight. They werefollowed through week 12 of the study. All study patients had chronic HCVinfection based on their medical history and the presence of detectable serumHCV RNA and elevated liver enzymes. More than half of the patients hadgenotype 1 HCV, the most difficult-to-treat strain. This study includedtreatment naive patients, patients who were partial responders to standardinterferon/ribavirin HCV treatment regimens, and patients who werenon-responders or treatment failures when given standard HCV regimens.
"Future hepatitis C therapy will likely require multiple mechanisms ofaction, including an immune modulating agent," said Dr. Lawitz. "Bavituximabhas a novel targeted immunomodulatory mechanism and if proven effective, ithas the potential to be complementary to emerging new anti-viral therapies forHCV infection."
Peregrine has initiated a new bavituximab trial in HCV patientsco-infected with HIV and is planning additional combination therapy HCVstudies.
Bavituximab is the first investigational agent in a new class ofanti-phosphotidylserine (PS) monoclonal antibody immunotherapeutics thattarget and bind to cellular components that are normally not present on theoutside of cells, but which become exposed on certain virally infected cellsand on the surface of enveloped viruses. Bavituximab helps stimulate thebody's immune defenses to destroy both the virus particles and the infectedcells. Since bavituximab
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