Antibody Bavituximab Well-Tolerated by HIV/HCV Coinfected People
An experimental monoclonal antibody that inhibits HCV replication
was safe and well-tolerated in a clinical trial of HIV positive
people coinfected with chronic hepatitis C, researchers
reported at EASL 2011.
is an investigational monoclonal antibody that targets phosphatidylserine
(a phospholipid component) on the membrane of virus-infected
cells. Preclinical studies have shown that this type of antibody
can inhibit viral replication and enhance immune response.
Phosphatidylserine is expressed on cells infected with a variety
of viruses -- including hepatitis
C virus (HCV), HIV,
influenza, and herpes viruses -- suggesting that targeted antibodies
could be beneficial in a number of diseases.
Prior studies found that single and twice-weekly intravenous
infusions of bavituximab up to 6 mg/kg were well-tolerated and
showed transient antiviral activity in people with chronic hepatitis
As reported at the European Association for the Study of the
Liver's International Liver Congress (EASL
2011) this month in Berlin, researchers then evaluated the
safety, tolerability, pharmacokinetics, and viral kinetics of
up to 8 weekly infusions of bavituximab in HIV/HCV coinfected
Below is an edited excerpt from a Peregrine
Pharmaceuticals press release describing the study and its findings.
Presents Phase Ib HCV/HIV Data on Single-Agent Bavituximab
Safe and Well Tolerated, Ongoing Phase II Trial Evaluating
Bavituximab With Ribavirin
Tustin, CA, and Berlin, Germany -- April 4, 2011 -- Peregrine
Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical
company developing first-in-class monoclonal antibodies for
the treatment of cancer and viral infections, today announced
data from its Phase Ib dose escalation safety study of bavituximab
in patients coinfected with chronic hepatitis C virus (HCV)
and HIV. In a poster presented at the 46th Annual Meeting
of the European Association for the Study of the Liver (EASL),
data show bavituximab administered as a single agent for 8
weeks was generally safe and well tolerated at all four dose
used as a single agent has demonstrated a consistent, acceptable
safety profile in three Phase I HCV trials to date, and we have
seen enhanced antiviral activity when using bavituximab in combination
with the antiviral agent ribavirin in several preclinical viral
disease models," said Joseph S. Shan, vice president of
clinical and regulatory affairs at Peregrine Pharmaceuticals.
"Our recently initiated randomized Phase II trial will
assess early virology response of genotype 1 HCV patients after
12 weeks of therapy combining bavituximab with ribavirin as
a potential alternative to the current interferon-based regimen."
Peregrine's Phase Ib safety study included 27 patients (85%
genotype 1 HCV) coinfected with HCV and HIV. Coinfected patients
typically have higher HCV viral loads and more rapid progression
compared to patients infected with HCV alone. Patient cohorts
received ascending dose levels of bavituximab weekly (0.3 mg/kg,
1.0 mg/kg, 3 mg/kg and 6 mg/kg) for up to 8 weeks. Adverse events
(AEs) were considered mild or moderate and were consistent with
other bavituximab trials. Three serious adverse events were
reported, two of which were drug-related (rash and hypersensitivity).
Patients were not premedicated. No dose-limiting toxicities
occurred and a maximum tolerated dose of bavituximab was not
reached. Although not a primary endpoint of this safety study,
HCV and HIV antiviral activity (> 0.5 log10 reduction)
were observed in all treatment groups during bavituximab therapy.
In an ongoing randomized Phase II HCV trial, Peregrine is evaluating
the 12-week early virologic response (EVR) rate of previously
untreated genotype-1 HCV patients treated with Peregrine's bavituximab
(0.3 mg/kg or 3 mg/kg) in combination with the antiviral drug
ribavirin (1000 mg) versus current standard of care, pegylated
interferon alpha-2a (180 mcg) and ribavirin. For further information
about this trial, which is being conducted outside of the U.S.,
please visit www.peregrinetrials.com or www.clinicaltrials.gov/ct2/show/NCT01273948?term=bavituximab&rank=3.
A copy of the poster is available at Peregrine's website www.peregrineinc.com/pipeline/cot.html.
About Bavituximab's Antiviral Approach
Bavituximab is the first in a new class of patented antibody
therapeutics that target and bind to phosphatidylserine (PS),
a specific phospholipid component of cell membranes. Bavituximab
helps reactivate and direct the body's immune system to destroy
infected cells and virus particles that exhibit this specific
phospholipid on their surface. Since their target is host-derived
rather than pathogen-derived, PS-targeting antibodies have the
potential for broad-spectrum antiviral activity and are also
expected to be much less susceptible to the viral mutations
that often lead to drug resistance.
Researchers have found that PS is exposed on the outer membrane
of cells infected with HCV, HIV, influenza, herpes viruses,
hemorrhagic fever viruses, respiratory syncytial virus, measles
as well as other viruses. A growing body of scientific publications,
including Nature Medicine and The Journal of Experimental
Medicine, has highlighted data on the role of PS and Peregrine's
PS-targeting therapies in infectious diseases.
About Peregrine Pharmaceuticals
Pharmaceuticals, Inc. is a biopharmaceutical company with a
portfolio of innovative monoclonal antibodies in clinical trials
for the treatment of cancer and serious viral infections. The
company is pursuing multiple clinical programs in cancer and
hepatitis C virus infection with its lead product candidate
bavituximab and novel brain cancer agent Cotara. Peregrine also
has in-house cGMP manufacturing capabilities through its wholly-owned
subsidiary Avid Bioservices, Inc. (www.avidbio.com),
which provides development and biomanufacturing services for
both Peregrine and outside customers. Additional information
about Peregrine can be found at www.peregrineinc.com.
Investigator affiliations: Infectious Diseases, Saint Michael's
Medical Center, Newark, NJ; Center for Viral Hepatitis, John's
Hopkins University, Baltimore, MD; Peregrine Pharmaceuticals,
Inc., Tustin, CA.
J Slim, MS Sulkowski, and JS Shan. Escalating repeat-dose study
of bavituximab in patients co-infected with chronic hepatitis
C virus (HCV) and human immunodeficiency virus. 46th Annual
Meeting of the European Association for the Study of the Liver
(EASL 2011). Berlin. March 30-April 3. Abstract
Peregrine Pharmaceuticals. Peregrine Presents Phase Ib HCV/HIV
Data on Single-Agent Bavituximab at EASL. Press release. April