Margie:
This is from an 8K filed recently.
Item 5. Other Events
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Recent Restructuring
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The Immune Response Corporation (the "Company") announced on June 21,
1999, the implementation of a restructuring plan primarily aimed at reducing
expenses while focusing the majority of the Company's resources on its late
stage programs of immune-based therapeutics for HIV ("REMUNE") and rheumatoid
arthritis. The Company's workforce will be reduced by approximately 30%.
The Immune Response Corporation will take a one-time charge against
earnings in the second quarter of approximately $650,000, or $0.03 per share.
The total decrease in expenses that results from the restructuring will
phase in over several quarters.
REMUNE
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The Immune Response Corporation has drug trials underway in which
REMUNE is used alone or in combination with major antiviral drugs. In
addition, the Company is conducting other clinical trials to obtain
additional data with respect to the use of REMUNE. The following table
summarizes the principal clinical trials The Immune Response Corporation has
recently conducted or is currently conducting with REMUNE.
PRINCIPAL CLINICAL TRIALS USING REMUNE
CURRENT OR RECENTLY COMPLETED
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Intended
Date Patient
Stage Initiated Enrollment Objectives
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Phase 3 1996 2,500 Intended to measure the ability of
Trial 806 (concluded REMUNE to impact HIV disease
May 1999) progression or progression to death. The
primary basis for concluding the trial was
due to lack of efficacy on clinical
endpoints.
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Phase 1 1996 32 Intended to measure safety and ability to
Pediatric stimulate an immune response in children.
Trial 808
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Expanded Access 1996 1,000 Intended to measure long-term safety.
Trial 903
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CURRENT INTERNATIONAL TRIALS
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Intended
Date Patient
Stage Initiated Enrollment Objectives
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Phase 2 1996 300 Intended to measure safety, HIV-specific
Thailand immune response and effects on CD4
Trial 2101 levels and viral load.
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Phase 2 1997 243 Intended to measure safety, HIV-specific
Spain immune response and effects on CD4
Trial 2102 levels and viral load.
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Phase 2 1998 30 Intended to measure HIV-specific
Switzerland immune response and effects on CD4
Trial 2103 levels and viral load during antiviral drug
usage.
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Phase 2 1998 40 Intended to measure HIV-specific
United Kingdom immune response and effects on CD4
Trial 2104 levels and viral load during antiviral drug
usage.
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The Company reported on May 17, 1999, that the Independent Data Safety
Monitoring Board ("DSMB") completed a second interim efficacy analysis of
Trial 806 to evaluate the immune-based therapy REMUNE when used alone or in
combination with other anti-HIV therapy. The primary efficacy endpoint for
this clinical trial was disease progression to an AID's defining condition or
death. The DSMB recommended that Trial 806 be concluded because differences
in clinical endpoints were not observed between treatment groups and because
extending the trial would be unlikely to provide sufficient additional
clinical endpoints to permit statistically significant differences between
the treatment groups to be observed in the near term.
As part of the second interim analysis of Trial 806, the DSMB also
reviewed surrogate marker data. This included some viral load data (level of
HIV RNA in plasma) from a subset of 435 patients, consisting of patients who
at the outset of the trial were taking Highly Active Anti-Retroviral Therapy
("HAART") and had low levels of viral load (baseline HIV-1 RNA less than 400
copies/mL). The data was based on samples drawn every six months, but also
included some additional data from samples drawn every three months from a
small number of these 435 patients. The DSMB determined that in this subset
of patients there was no statistically significant difference in viral load
between those taking HAART and those taking HAART with REMUNE. In addition,
other surrogate marker data was analyzed by the DSMB and significant
differences were observed with respect to lymphocyte proliferation and CD4
cell count. There are a large number of plasma samples that have not been
tested for viral RNA. It is possible, that this additional information might
provide alternative findings and the DSMB encouraged testing these specimens
with additional analyses.
The Company also previously reported that a separate analysis by the
Company and Agouron Pharmaceuticals, Inc. ("Agouron"), a wholly owned
subsidiary of Warner-Lambert Company, of a cohort of 250 patients randomly
pre-selected from Trial 806 for surrogate marker analysis, showed a
significantly greater reduction in viral load after 48, 96 and 120 weeks of
treatment and significantly greater increases in lymphocyte proliferation in
those who received REMUNE compared with those who did not. The data was
based on samples drawn from the patients in the 250 patient cohort every
three months. Since the 250 patient cohort was randomly pre-selected, the
Company believes that it was
representative of the 2,500 patients in the study and included both patients
who were and were not using HAART at the outset of the trial and thus had
varying viral load levels. The analysis of this 250-patient cohort was
completed after the DSMB had reached its findings and was not reviewed by the
DSMB. It is possible that the results can be used, in conjunction with other
data, to support an application for the marketing of REMUNE in the U.S. This
data has not yet been presented to the United States Food and Drug
Administration ("FDA"), but the Company and Agouron plan on submitting the
results to the FDA for its consideration.
The Company is considering additional analyses to better understand the
disparate viral load findings between the different patient populations
analyzed in Trial 806.
Agouron has advised the Company that it plans to initiate two pivotal
trials of REMUNE in light of an understanding previously reached with the FDA
that an application for the marketing of REMUNE could be submitted based upon
favorable virological endpoints. If successfully concluded, these trials
could possibly be used to support an application for marketing REMUNE in the
U.S. Agouron also advised the Company that it expects to commence enrollment
in North America and Europe for one of these trials in the third quarter of
1999 and enrollment in the other trial in the year 2000. If initiated and
successfully concluded, the results from these trials will not be available
until mid-2001.
Trinity Medical Group Co., Ltd. ("Trinity"), of Bangkok, has license
rights to develop, market and distribute REMUNE in Thailand and other
Southeast Asian countries pursuant to an agreement with The Immune Response
Corporation. Trinity is sponsoring its own independent ongoing Phase 2,
double-blind, placebo-controlled clinical trial with approximately 300
HIV-infected individuals. This clinical trial is being conducted by
investigators from Mahidol University in Bangkok, Thailand, and is monitored
by an independent data safety monitoring board and conducted under the
guidelines of the Thailand Ministry of Public Health.
The Company is currently conducting a 243 patient double-blind,
placebo-controlled clinical trial in Spain which was initiated in 1997 and is
intended to study virologic endpoints and CD4 levels. The trial was not
submitted as a pivotal trial to the FDA, when it was initiated, because the
FDA did not accept virologic endpoints as a basis to support an application
for marketing at the time; however, the protocol was submitted to the FDA
under the REMUNE Investigational New Drug ("IND") application. If
successfully concluded, it is possible that the results from this trial can
be used, in conjunction with other data, to support an application for the
marketing of REMUNE in the U.S.
In addition, REMUNE is being tested in Trials 808 and 903 in the United
States and in Trials 2103, and 2104 with other HIV therapies in Switzerland
and the United Kingdom. The Company does not believe that any of these
trials, other than the trials to be initiated by Agouron and possibly the
trial in Spain, can be used as pivotal trials for an application for the
marketing of REMUNE in the U.S; however, the Company does believe that the
data from some of these trials might be used to support applications for the
marketing of REMUNE in countries other than the U.S.
The Immune Response Corporation is also continuing its efforts to move
ahead from its non-binding terms of collaboration with the University of
Maryland Biotechnology Institute, announced May 10, 1999, toward a binding
agreement regarding selected chemokines and HAF (hCG associated factor)
technology discovered by Dr. Robert Gallo and his associates at the Institute
of Human Virology ("IHV"). The Company expects to seek additional funding to
support this collaboration.
This Form 8-K contains forward-looking statements. Actual results
could vary materially from those expected due to a variety of risk factors,
including whether or when Agouron will initiate or successfully complete
additional pivotal trials of REMUNE, whether, even if successfully completed,
the data from these trials would support an application for the marketing of
REMUNE, whether REMUNE will receive necessary regulatory approval, whether
the Company will enter into a binding agreement with the University of
Maryland Biotechnology Institute and those risks set forth from time to time
in The Immune Response Corporation's SEC filings, including but not limited
to its report on Form 10-K for the year ended December 31, 1998. The Company
undertakes no obligation to publicly release the result of any revisions to
these forward-looking statements which may be made to reflect events or
circumstances after the date hereof or to reflect the occurrence of
unanticipated events.
Walt |
