The Immune Response Corporation Announces Publication of Study
Suggesting That REMUNE(TM) Induces HIV-1 Specific T Helper Immune
Responses That Correlate With Control of Virus
CARLSBAD, Calif., April 23 /PRNewswire Interactive News Release/ -- The Immune
Response Corporation (Nasdaq: IMNR) announced the publication of data today that
suggest REMUNE(TM) (HIV-1 Immunogen), an investigational immune-based therapy,
induces HIV specific (T helper cells) immune responses that correlate with
control of virus (viral load, the amount of HIV in the bloodstream) in
HIV-positive individuals. An analysis of a protocol defined random cohort from a
Phase 3 study showed that patients treated with REMUNE demonstrated a
statistically significant reduction in viral load at multiple time points
throughout the trial, regardless of concomitant antiretroviral drug therapy. The
results of the study appear in the April edition of HIV Medicine
(www.BlackwellScientific.com), the official Journal of the European AIDS
Clinical Society and the British HIV Association.
The protocol defined random cohort involved 252 HIV-positive individuals who
received injections of either REMUNE or a placebo (Incomplete Freund's Adjuvant)
in addition to un-restricted anti-retroviral drug use. A 2500-patient,
multi-center, double-blind, adjuvant-controlled, clinical endpoint Phase 3 study
begun in 1996 included this cohort study that was designed to determine the
relationship between viral load (amount of virus in the blood) and HIV-specific
immunity.
Viral load was measured as HIV-1 plasma RNA levels every 12 weeks, more
frequently than in other patients in the larger study (whose viral load was
measured every 24 weeks). In the REMUNE treated group, a significantly greater
decline in viral load (p<0.05) at multiple time points was observed. These
differences in viral load were not significant for the first two time-points but
were observed at week 36 (p=0.01), and were maintained at weeks 48 (p=0.02), 60
(p=0.02), 84 (p=0.001), 96 (p=0.004), and 120 (p=0.03). The authors believe that
the apparent 36-week "lag time" between the initial treatment with REMUNE and a
significant reduction in viral load may suggest that the immune system requires
a period of time after immunization to organize specific immune forces against
the virus. Lymphocyte Proliferation Assays (LPAs) were also performed on blood
samples taken every 24 weeks. LPAs are a common measure of the ability of the
immune system to respond to HIV via T helper cells. LPA test results indicated
that HIV-specific T helper cell immune responses were generated only in the
REMUNE treated group (p<0.0001). In the REMUNE treated group, LPA to HIV
antigens after immunization (24 weeks) correlated with the amount of virus in
the blood (week 24, r=-0.32, p=0.002; week 48, r=-0.42, p=0.001; week 72,
r=-0.29, p=0.05; week 96, r=-0.35, p=0.003; week 120, r=-0.53, p=0.001).
"Since many of these patients were taking potent antiretroviral drugs and were
permitted to switch drugs ad lib, we expected to see a decrease in viral load in
both the placebo group and the REMUNE group," said John Turner, M.D., of the
Graduate Hospital (Philadelphia, PA) and principal author of the study. "The
data indicate, however, that patients treated with REMUNE tended to exhibit an
even greater decrease in viral load when compared to the placebo group. The
random cohort was sampled every three months for viral load. I believe that it
is possible that the less frequent viral load sampling on the larger cohort
which was obtained every six months (including a majority of the 435 patients on
potent antiretroviral therapies at the beginning of the study), where little
difference between the treatment groups was observed, impacted on the ability to
detect effects of immunization on viral load. This is most likely due to the
multiple antiviral drug switching which occurred during this trial. Most
importantly, there was a correlation between the induced HIV specific T helper
immune responses and control of the amount of virus in the blood. These findings
further support the plausibility of the results in the random cohort. As the
leading enrolling investigator in study 806, I am pleased that the details of
this important information have been peer reviewed by HIV clinical experts and
are now available to the HIV and scientific communities."
"Most HIV-positive individuals lose the ability to recognize and respond to HIV
soon after becoming infected despite treatment with antiretroviral drugs. The
LPA results indicate that REMUNE may restore HIV specific T helper immune
responses," said Dr. Turner. "This is significant because HIV-1 specific immune
responses, as shown by other investigators, are associated with the ability to
control the level of virus in the blood in HIV-positive individuals who do not
progress to AIDS. We observed for the first time a correlation between
vaccine-induced HIV specific T helper responses in chronic HIV infection and
control of virus."
The 252 HIV-positive individuals involved in the published study were a randomly
selected subset from a larger 2500-patient, multi-center, double-blind,
adjuvant-controlled Phase 3 clinical study begun in 1996. All participants in
the study were asymptomatic and had CD4 cell counts of 300-549cc/mm(3). There
were no prerequisites as to the use of antiretroviral drug therapy; patients
were allowed to take any combination of drugs and to switch combinations
throughout the duration of the trial. Patients were randomized to receive
intramuscular injections of either REMUNE or a placebo (Incomplete Freund's
Adjuvant) once every 12 weeks for 120 weeks. The trial was discontinued in May
of 1999 when an independent data safety monitoring board determined that the
trial would not reach statistical significance on the primary endpoints of
progression to AIDS related illnesses or death (see Company Form 8-K dated May
14, 1999 and filed with the SEC on July 6, 1999). The trial was designed for a
6% per year rate of progression to AIDS or death as endpoints. During the trial,
because of the fewer than expected clinical events, the endpoint definition was
modified to include non-AIDS defining events. When the trial was stopped it was
determined that the actual rate of progression to AIDS or deaths was <1% per
year.
REMUNE is currently the subject of several clinical trials, including a Phase 2
trial being conducted in Spain and a Phase 3 trial sponsored by the Company's
partner Agouron Pharmaceuticals, Inc. (a Pfizer company) to evaluate REMUNE's
effect on viral load when administered in combination with potent antiviral drug
therapy. Impact on viral load is now a measure of efficacy that is accepted by
the Food and Drug Administration for approval of REMUNE. |
