Avid Bioservices Inc (CDMO)

[jazzbeerman]

Sean,




I thought it was covered nicely by Godofsky.
(below)



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http://www.hcvadvocate.org/news/reports/AASLD_2006/Abstracts/parallel%20session%2018_HCV%20preclinic...


127. Phase I single-dose study of bavituximab, a chimeric anti-phosphatidylserine monoclonal antibody, in subjects with chronic hepatitis C.

E. W. Godofsky; J. S. Shan.

Background:

Bavituximab is a novel monoclonal antibody that specifically targets phosphatidylserine (PS) on the outer surface of the plasma membrane of virally infected cells and enveloped viruses. Once bound, it is believed to direct the host’s immune system to clear virally infected cells and viruses. Its antiviral activity has been previously demonstrated in animal models of murine cytomegalovirus and pichinde virus.



Aim:

To determine the safety, tolerability and pharmacokinetics of a single intravenous (IV) infusion of bavituximab in a phase I, open-label, dose-escalation study in subjects with chronic HCV infection who failed to respond to or relapsed after pegylated interferon plus ribavirin combination therapy.



Methods:

Sequential cohorts of 6 subjects were given a single 90 min IV infusion of bavituximab at 0.1, 0.3, 1, 3 or 6 mg/kg and were followed for 12 weeks. Vital signs, physical exams, safety laboratory parameters, serum bavituximab levels were monitored and serum HCV RNA levels were measured by NGI SuperQuant.



Results:

The infusion was safe and well tolerated by all subjects. All adverse events were mild or moderate in severity, except for 1 report of severe headache at 1 mg/kg and 1 of severe vertigo at 3mg/kg, both unrelated to study drug. The majority of AEs were considered not related to study drug, with the most common being injection site bruises, nausea, rhinitis, and headache. There were no laboratory AEs except for expected subclinical transient prolongation of aPTT for the 3 and 6 mg/kg dose groups on day 1 postdose. After IV infusion, bavituximab reaches Cmax at 1h postdose with a mean elimination half-life of ~31h. There was a trend towards a bimodal decrease in mean serum HCV RNA levels. The first decrease was seen within 24 hours postdose and the second began around day 4 and appeared sustained up to several weeks in some subjects. Serum cytokine analyses are ongoing.



Conclusions:

Single IV doses of bavituximab up to 6 mg/kg were safe and well tolerated. It has a predictable pharmacokinetic profile. The transient reductions in serum viral load were consistent with the proposed mechanism of immune stimulation. Unlike conventional therapy, bavituximab is a unique therapeutic that targets viruses and virally infected cells by channeling host’s defense against them. Since it does not target viral proteins, bavituximab is unlikely to elicit traditional viral resistance.




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