The AIDS treatment research establishment is FINALLY
admitting that they are shutting down T-cell proliferation
and suppressing the immune system. When will they finally
admit that the viral load test is an invalid marker for
predicting disease progression when it is manipulated by
shutting down immune responses?
Many months ago I posted a commentary with the statement that
the protease inhibitors were interfering with the metabolism
of the cells similar to cancer chemotherapies. In response,
Carlton Hogan, who is involved in AIDS drug clinical trials
and often speaks on behalf of the drug activist crowd, said
that I didn’t know what I was talking about. Well, Carlton,
here are some of the lead researchers in AIDS saying the
exact same thing. Any questions now?
For example, the article points out:
"As BCX-34 acts selectively on replicating T-cells, and
not on resting T-cells, it may preferentially target
rapidly multiplying infected T-cells in vivo to help
reduce viral load in HIV patients. Our in vitro
research in peripheral blood cells infected with HIV
showed that BCX-34 significantly inhibited viral
replication."
Two big problems: (1) we need to activate T-cells to handle
antigen presentation and maintain a competent immune
response, and (2) the focus on T-cells as the single factory
of HIV production is outdated.
Now they admit:
"This particular trial will evaluate BCX-34 in patients
with early stage disease in which a reversible change in
T-cell counts should not compromise the patient’s immune
system,…"
They are admitting that they will be LOWERING the population
of T-cells as a desirable therapy in those who are healthy
and recently infected. As usual, they claim that this is yet
another therapy that "should not" compromise the patient’s
immune system. Excuse me, but can anyone explain how
suppressing the activation of T-cells will NOT compromise the
immune system?
Clean, simple and honest: STOP THE PROLIFERATION OF T CELLS
RESPONDING TO INFECTIONS!!!!
At least researcher George Shaw is being honest:
"As BCX-34 acts selectively on replicating T-cells, and
not on resting T-cells, it may preferentially target
rapidly multiplying infected T-cells in vivo to help
reduce viral load in HIV patients. Our in vitro
research in peripheral blood cells infected with HIV
showed that BCX-34 significantly inhibited viral
replication."
Unfortunately, there will be plenty of fools lining up to be
"saved" by these idiots who are simply using HIV+
undesirables as an experimental platform for cancer drugs.
And they will be led to their early demise by the drug
activist ACT UP sell-out organizations, the drug company
information clearing house known as Project MisInform and
with the cooperation of anti-science idiots like John James
of the AIDS Treatment News.
===================================
BIRMINGHAM, Ala.–(BW HealthWire)–April 30, 1997–
Preclinical Studies Support Novel Immunomodulatory
Therapeutic Approach
BioCryst Pharmaceuticals (Nasdaq: BCRX) today announced the
initiation of a Phase I feasibility study using an oral
formulation of its lead drug, BCX-34, for the treatment of
HIV in combination with standard antiretroviral therapy. BCX-
34 is a small-molecule drug that modulates the proliferation
of T-cells. Based on preclinical studies, scientists at the
University of Alabama at Birmingham (UAB) and BioCryst
theorize that BCX-34 may reduce HIV load in the bloodstream
by inhibiting the replication of infected T-cells. The study,
which is being conducted under Michael S. Saag, M.D. at UAB,
is designed to obtain safety, pharmacology and biological
data.
"Plasma HIV load increases through the proliferation of
infected T-cells, which replicate at a faster rate than
healthy T-cells," said George M. Shaw, M.D., Ph.D.,
Professor of Medicine and Microbiology, and Deputy Director,
Center for AIDS Research at UAB, who conducted the
preclinical research using BCX-34 against HIV. "As BCX-34
acts selectively on replicating T-cells, and not on resting
T-cells, it may preferentially target rapidly multiplying
infected T-cells in vivo to help reduce viral load in HIV
patients. Our in vitro research in peripheral blood cells
infected with HIV showed that BCX-34 significantly inhibited
viral replication."
Clinical research has shown that viral load in the
bloodstream correlates with disease stage, can predict
subsequent clinical outcome, and acts as a direct indicator
of the effect of antiretroviral treatments. While potent
combination antiviral drug therapy has led to significant
clinical improvements in patients with late stage disease, it
is not clear that these same effects can be achieved in
earlier-stage patients where the benefit to risk ratio of
combination antiretroviral therapy may be less. In addition,
there is growing recognition that replication of infected T-
cells plays an important role in sustaining HIV-1 production
in vivo at all stages of disease, raising the possibility
that inhibition of T-cell activation can potentially
complement antiretroviral therapy. Still another potential
advantage gained by inhibiting T-cell activation and HIV
replication may come from a delay in the emergence of drug-
resistant virus, an outcome that limits the effectiveness of
all currently approved antiretroviral therapies. Thus, BCX-34
could potentiate the effectiveness of all currently available
antiretroviral drugs and drug combinations.
"Unlike anti-viral therapies targeting HIV, BCX-34 acts
against the virus’ T-cell host and consequently should not be
affected by drug resistance resulting from viral mutation,"
said George A. Omura, M.D., Vice President, Clinical
Development and Medical Director at BioCryst. "Ongoing open
label studies with oral BCX-34 in other indications have
shown the drug to be safe and to have reversible
immunosuppressant properties. We therefore believe it
presents a safe and potentially effective approach to
reducing viral load in HIV-infected patients.
"This particular trial will evaluate BCX-34 in patients with
early stage disease in which a reversible change in T-cell
counts should not compromise the patient’s immune system, and
where combination immunomodulatory and antiviral therapy may
have the greatest clinical impact. Patients will be closely
monitored through the treatment regimen to ensure that their
T-cell counts remain stable," he added.
Cohorts of seven HIV-infected patients with CD4 T-cell counts
greater than 400 cells/mm3 will be enrolled in the Phase I
study. Five patients will be dosed with oral BCX-34 and two
will receive placebo. Patients in the initial drug cohort
will receive a daily dose totaling 20mg (10mg per dose twice
daily) for 14 consecutive days, followed by a two week
observation period, with an increasing dose to 40mg in a
subsequent course. Over the course of the trial, subsequent
cohorts will receive a higher dose level, until the maximum
tolerated dose is established. Patients will also be treated
with other antiretroviral drugs AZT and 3TC. BCX-34 therapy
will be discontinued in any patient whose overall CD4 T-cell
count decreases more than 25 percent from baseline.
"It is our hope that this feasibility study will duplicate
the proof of principle obtained in preclinical studies and
will support the clinical utility of oral BCX-34 as an anti-
HIV therapy," said J. Claude Bennett, M.D., President and
Chief Operating Officer of BioCryst. "HIV represents the
third disease target for our oral BCX-34 clinical program
targeting aberrant T-cell proliferation and autoimmune
diseases. We are currently preparing IND applications for
additional indications and may begin other clinical trials
later this year."
BioCryst’s lead drug, BCX-34, is in clinical trials with both
topical and oral formulations. The Company is currently
conducting two multi-center Phase III clinical trials with
topical BCX-34 for the treatment of cutaneous T-cell lymphoma
(CTCL) and psoriasis, and two Phase I/II clinical trials with
an oral formulation of BCX-34 to treat T-cell cancers and
psoriasis. These diseases and other disorders, including
rheumatoid arthritis and transplant rejection, are associated
with the proliferation of T-cells.
Founded in 1986, BioCryst Pharmaceuticals, Inc. designs and
develops novel small-molecule pharmaceuticals using
structure-based drug design, an approach to drug discovery
that integrates advanced biology, biophysics and medicinal
chemistry. The Company is developing drug treatments for
immunological and viral diseases. In addition to its T-cell
inhibition program, the Company is advancing two preclinical
programs to develop drugs to inhibit the influenza
neuraminidase enzyme associated with flu infection, and
activation of the complement signaling pathway implicated in
a number of immunological and cardiovascular diseases.
This press release contains projections or other forward-
looking statements regarding future events or the future
financial performance of the Company. These statements are
only predictions and the actual events or results may differ
materially. Please refer to the documents BioCryst files from
time to time with the Securities and Exchange Commission,
specifically BioCryst’s most recent Form 10-K and Form 10-Q.
These documents contain and identify important factors that
could cause the actual results to differ materially from
those contained in the projections or forward-looking
statements.
BW1101 APR 30,1997