HCV
Bavituximab Shows Promising Anti-Viral Activity in Monotherapy HCV Trial
By Peregrine Pharmaceuticals, Inc
Jun 8, 2006 - 6:18:00 AM

Peregrine Pharmaceuticals, a biopharmaceutical company developing targeted therapeutics for the treatment of cancer and hepatitis C virus infections, today reported top-line results on the effect of bavituximab (formerly Tarvacin) on viral RNA serum titers when administered as single dose monotherapy in a Phase Ia study in patients with chronic hepatitis C virus (HCV) infection. In this analysis, bavituximab showed signs of anti-viral activity at all four study dose levels, and it also showed evidence of a prolonged anti-viral effect.

These preliminary efficacy data follow positive safety data from the Phase Ia study that Peregrine reported on February 27, 2006, indicating that bavituximab was well tolerated, with no dose limiting toxicities observed. Peregrine also announced today two additional milestones in the bavituximab HCV clinical program. First, the company has completed the treatment phase of an additional, higher dose cohort that was added to the Phase Ia HCV study after the first four cohorts were complete, and second, it has begun dosing patients in a new Phase Ib repeat dose study in HCV patients.

In the Phase Ia study, more than 90% of the subjects were infected with the genotype 1 form of HCV, which is the most common and difficult to treat strain of the virus. All participants had failed or relapsed after receiving standard-of-care treatments. Subjects were administered bavituximab at 0.1, 0.3, 1 or 3 milligram per kilogram (mg/kg) of body weight.

After a single dose of bavituximab, among patients treated with the higher 1mg/kg and 3mg/kg dose levels, 50% achieved a greater than 75% (0.6 log) reduction in serum HCV RNA with a maximum 97% (1.5 log) reduction. These patients had an average reduction in serum HCV RNA levels of 0.8 log during the course of the 12-week follow-up period. Signs of anti-viral activity were seen at all dose levels including the initial dose of 0.1mg/kg. Even at this low dose, one-third of patients experienced a greater than 75% (0.6 log) reduction in serum HCV RNA levels.

Bavituximab also showed signs of durable anti-viral activity after a single dose, with some subjects achieving a greater than 80% (0.7 log) reduction in viral load by day four and maintaining a greater than 60% reduction in serum HCV levels up through the end of the study at week 12.

"This preliminary evidence of anti-viral activity in this first-in-human single dose study of bavituximab is very encouraging," said Dr. Eliot W. Godofsky, principal investigator of the Phase Ia study, and director of the University Hepatitis Center in Sarasota Florida. "Bavituximab is a potentially novel approach to treating chronic hepatitis C infection, one with a unique mechanism of action that should complement both existing and investigational therapies in development. Based on its safety profile to date and these promising signs of anti-viral activity, we look forward to working with Peregrine to assess bavituximab in the repeat dose trial, as well as its potential for use in combination regimens to control and ultimately eradicate HCV."

These initial efficacy findings for a single dose of bavituximab are noteworthy for several reasons. First, the rapid virus production and turnover characterizing HCV infection typically limit the impact of a single dose of any anti-viral drug. Second, preclinical data supports that bavituximab's unique mechanism of action, which mobilizes the body's immune system to attack the hepatitis C virus, is likely to be most effective when administered as part of a multiple dose regimen. Third, most other investigational drugs for HCV infection have reported initial efficacy results following multiple dose or combination regimens that include standard-of-care therapies. In this study bavituximab was administered as monotherapy to patients who had failed standard treatment. In view of these factors, the anti-viral activity demonstrated in this single dose, monotherapy study is all the more encouraging.

"We are delighted with these first positive indicators of bavituximab's anti-viral potential in HCV patients," said Steven W. King, president and CEO of Peregrine. "The initial human results for this first-in-class novel agent are very promising. Its excellent overall safety profile to date, early evidence of anti-viral activity and signs of prolonged duration of activity give additional impetus to our efforts to advance bavituximab as a potential new therapy for the treatment of HCV and other serous viral infections."

Joseph Shan, Peregrine's executive director of clinical and regulatory affairs, added, "These first efficacy results in humans are particularly exciting because researchers did not expect to see much anti-viral activity after a single dose of drug, based on our experience in lethal animal disease models such as Lassa fever. Bavituximab demonstrated good anti-viral activity in these studies, but only after administration of multiple doses. Based on the results reported today, the drug's anti-viral potential may be even more promising in humans than the animal models suggest."

Patients in the fifth dosing cohort (6mg/kg) of the Phase Ia HCV study are currently in the 12-week follow-up period, and data from this group will be available later this year. The repeat dose Phase Ib HCV study that is underway is designed to evaluate multiple doses of bavituximab for safety as well as assessing changes in serum HCV RNA levels. Enrollment in this study is expected to be completed by the end of the year.

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