Saquinavir: newest weapon in the antiviral arsenal.

AIDS: Saquinavir, the first of the protease inhibitors on the market, is a product of both an innovative product design and a growing dissatisfaction with the other anti-HIV products on the market. Saquinavir received Food and Drug Administration (FDA) approval in record time, 97 days. The design process for the drug is detailed, including specifications. Saquinavir, sold under the Hoffman-LaRoche label, Invirase, was computer-designed because of its ability to cleave to a protease site. Large-scale studies are currently underway, and the manufacturer has made the drug available through a compassionate treatment program since April 1994. Saquinavir's limited availability due to manufacturing problems appears to be resolved, and Hoffman-LaRoche reports that the synthesis process now takes less than a year.^ieng

Europe out of step with the US.

AIDS: The disparity in the availability of AIDS drugs between the United States and Europe is frustrating to members of the European AIDS Treatment Group, among others. It is hoped that the newly-created European Medicines Evaluation Agency (EMEA) will streamline drug approval for the European Union overall, since previous approvals were done on a country-by-country basis. Although alternative methods of drug approval in Europe cause apprehension, it is hoped that a system will be created that will deliver drugs quickly without sacrificing the physician and patient guideline requirements.^ieng

Saquinavir (Invirase): first protease inhibitor approved--reimbursement, information hotline numbers.

AIDS: Saquinavir, developed by Hoffmann-LaRoche under the trade name Invirase, is the first protease inhibitor to be approved by the Food and Drug Administration (FDA) for use in combination with one or more unspecified nucleoside analogs. Rifampin should not be taken with saquinavir, and rifabutin should be only cautiously used in combination with saquinavir. Protease inhibitors have shown T-cell increases and viral load reductions similar to AZT when taken at the present low dosage. Research is being done on a new formulation which would deliver more effective amounts. The cost of saquinavir and other new drugs may be prohibitive, especially as the standard treatment changes from one drug (AZT) to combinations of drugs. Physicians and patients should call the Roche HIV Therapy Assistance Program for more information.^ieng

European hurdles for saquinavir.

AIDS: European authorities want Hoffmann-LaRoche to offer a higher dose of saquinavir than what is currently offered (1,800 mg). A Stanford University study will lead U.S. physicians to prescribe 3,600 mg or even 7,200 mg per day to achieve greater antiviral effect. Hoffmann-LaRoche argues that it has no large-scale data supporting larger dosages. Activists urge the company to look at a nested data collection study within the expanded access program to alleviate questions about safety. Meanwhile, the company is supplying Europe with saquinavir on a compassionate-release basis.^ieng

Lottery opens 2,000 slots for protease trial.

AIDS: Hoffman-LaRoche has announced the opening of a second patient lottery for its Invirase International Compassionate Use Program. The lottery is for protocol SV14974, which is studying saquinavir treatment, both as a monotherapy and in combination with other antiretroviral drugs. Interested physicians should call the Roche Data Coordinating Center for more information.^ieng

Protease inhibitor: Roche lottery deadline July 21.

AIDS: Hoffmann-La Roche has announced details of the Invirase International Compassionate Treatment Program, which will distribute saquinavir (brand name, Invirase), a protease inhibitor. Saquinavir will be made available to 2,280 U.S. patients with a CD4 (T-helper) count under 300 who no longer benefit from approved antiretroviral drugs (AZT, ddI, ddC, and d4T), and who meet other criteria. Sixty percent of the slots will be reserved for persons with a T-helper count under fifty. In addition, Roche has set up a lottery in case more people apply for the drug. Physicians must enter their patients by July 21, 1995. The author notes, however, that previous data on saquinavir at the suggested dosage levels to be used in this program have not been significant. The drug appears to be safe and effective, but at larger doses. Roche may make saquinavir a better drug by using new data to show doctors how to use it more effectively. There are concerns that patients using saquinavir alone are more likely to develop resistance to it, which means they may not be able to benefit from future protease inhibitors. However, Roche claims that new data shows that saquinavir does not cause resistance to other protease inhibitors, and that the development of resistance to saquinavir itself can be reduced by using it in combination with AZT.^ieng

Hoffmann-LaRoche announces international compassionate treatment program for saquinavir.

AIDS: Hoffman-LaRoche has decided to supply saquinavir to 4,000 patients who are not eligible to enroll in ongoing clinical trials but who may benefit from the investigational treatment. The plan is an open-label safety program that is international in scope. U.S. patients can enroll in the program through their physician. Due to the limited supply of saquinavir, a patient lottery system has been developed to distribute the drug in the U.S. and Canada. Information on the specifics of the program are available by calling (800) 332-2144 or faxing (800) 332-7644. Information on the Canadian arm, which has different lottery criteria, can be obtained by calling (800) 257-3741. To be considered for the U.S. lottery, registration forms must reach the Roche Data Coordinating Center at Parexel by 5pm, EDT, July 21, 1995.^ieng