physicians, journalists and
AIDS treatment advocates from across Europe met today to learn about genotyping, a new
technology that will give doctors and patients unprecedented ability to maintain their
attack on HIV. Researchers at a workshop sponsored by F. Hoffmann La Roche Ltd of
Basel, Switzerland, also provided attendees with extensive data on Roches powerful
new protease inhibitor, FORTOVASE« (saquinavir), which is now being launched
across the European Union. FORTOVASE is an enhanced formulation of INVIRASE«
(saquinavir mesylate), which was the first-generation formulation of saquinavir.
Genotype testing applies the cutting-edge technologies of PCR and DNA sequencing to
generate data that tells physicians and patients which mutations have developed in an
individual's HIV strain. These mutations, which can lead to resistance to various anti-HIV
drugs, may have developed over time in response to therapy or may have already existed in
the HIV strain when a person was first infected.
"By diagnosing these mutations early, before the number of mutations begins to
escalate, genotype testing offers physicians and patients the unprecedented ability to
maximize anti-HIV therapy for each patient according to his or her needs," said Prof.
Charles Boucher of the Department of Virology, University Hospital, Utrecht, The
"Now we can see exactly which mutations are present, and hopefully improve
treatment for patients by cutting out the drugs that dont work as a consequence of
resistance; we can add drugs that do. Until now, weve had to change all of the
drugs, forcing patients to rapidly use up the repertoire of available drugs."
Experts Collaborate to Facilitate Use of Genotype Testing -- the GREAT Study
While experts are excited about the insight that genotype testing offers, the field
itself is complex. In order to ensure that genotype data is used in the most effective way
for the patient, Roche is collaborating with Virology Networks of Utrecht, The
Netherlands, and the company that recently launched its HIV Genotyping System, PE
Biosystems of Foster City, California.
The collaboration centers around the GREAT trial -- Genotypic Resistance Evaluation to
Aid Therapy-switching -- a Virology Networks trial that will evaluate the benefit of
resistance testing in the HIV treatment setting, and will include a variety of different
treatment approaches and a wide range of anti-HIV medications.
The GREAT trial will also test the prototype RetroGram Decision Support Software
in real-world settings. This experimental software, designed jointly by Virology Networks
and Roche and developed by UK-based decision support specialists InferMed, uses an
electronic rule-based algorithm to interpret genotype data and guide physicians and
patients in treatment decisions.
"Interpreting complex genotype data -- which specific genes have specific
mutations, what those mutations mean for the potential success of individual drugs -- can
be very challenging," said Jonathan Schapiro, MD, Clinical Instructor in Medicine at
the Stanford University School of Medicine, in Stanford, California, and Director, AIDS
Services at the National Hemophilia Center in Tel Hashomer, Israel. "The great
complexity of understanding specific resistance patterns may make the clinical use of
genotypic assay results difficult for the busy practicing physician. Systems interpreting
these patterns would therefore assist in making this truly a clinical tool."
Roche is providing funding to Virology Networks for the GREAT study; the company is
also providing AMPLICOR HIV-1 MONITOR viral load and proviral DNA tests. PE
Biosystems is collaborating with Virology Networks and Roche in the GREAT study by
supplying its research-use-only HIV Genotyping System, instruments and expert technical
FORTOVASE, Powerful New Protease Inhibitor, Is Launched in the E.U.
In addition to the GREAT trial, Roche is sponsoring several initiatives to help
physicians and patients understand how genotyping fits into the HIV treatment paradigm. A
number of these initiatives will include FORTOVASE, Roches newly available protease
inhibitor, to demonstrate how genotyping can help optimize treatment choices at all stages
of HIV infection.
FORTOVASE has been extensively studied in a variety of patient populations and in
combination with other agents. These trials have shown its improved efficacy compared to
its predecessor, INVIRASE; demonstrated its power and durability when compared to the
leading protease inhibitor, indinavir; and proven its flexibility and tolerability in
combination with three-drug and four-drug regimens.
Roche has presented data from six studies in which FORTOVASE treatment was initiated in
combination with two nucleoside analogs, at least one of which was new for the patient. In
this "standard of care" setting, FORTOVASE showed impressive, consistent results
with 76%to 90% of antiretroviral-na´ve patients achieving suppression of viral load to
below the limit of detection of the AMPLICOR HIV-1 MONITOR PCR assay at
24 weeks (on-treatment analysis <400 copies/ml; 55-83% <400 copies/ml by the more
stringent intent-to-treat analysis, in which missing values are considered failures).
In those studies that included nucleoside-analog pre-treated patients, 64%-74% of
patients achieved a viral load reduction to below the limit of quantification by
on-treatment analysis and 53%-64% by intent to treat.
The pivotal activity trial for FORTOVASE demonstrated durability of benefit out to 72
weeks of FORTOVASE therapy, with 80% of patients achieving a reduction in HIV-RNA to
<400 copies/ml by on-treatment analysis and 50% by intent-to-treat analysis.
FORTOVASE is already available in several markets worldwide, including the United
"These studies have confirmed the usefulness of FORTOVASE for patients who are
treatment-na´ve as well as for those who are treatment-experienced and need additional
options. Physicians and patients need to know that there are effective and durable
treatment options available during the course of HIV disease," said Dr. Peter Carey
of the Department of Genitourinary Medicine, Royal Liverpool University Hospital,
Liverpool, United Kingdom. Dr. Carey is a lead investigator in the Roche TIDBID study,
which compared twice-daily FORTOVASE dosing to the standard three times-daily dose.
Thirty-two week data from the TIDBID study indicate that twice-daily dosing with
FORTOVASE may provide effective treatment option for patients who want the flexibility of
twice-daily versus three times-daily dosing.
The Roche Group is a world leader in research-based health care with principal
businesses in pharmaceuticals, diagnostics, vitamins, and fragrances and flavors. Roche
discovers, develops, and markets prescription drugs in key therapeutic areas such as
virology, infectious diseases, cardiology, oncology, transplantation, and obesity.