Major Advance in HIV Management: Pan European HIV Genotyping Thrust Launched

Roche Announces Collaborative Thrust Into HIV Genotyping;

FORTOVASE Is Launched in European Union

GENEVA, 8 May 1999 – More than 350 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 Roche’s 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 Netherlands.

"Now we can see exactly which mutations are present, and hopefully improve treatment for patients by cutting out the drugs that don’t work as a consequence of resistance; we can add drugs that do. Until now, we’ve 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 support.

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, Roche’s 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 States.

"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.