Business Wire - Thursday May 6, 1999
Expanded access programs are part of an effort by government health agencies and the pharmaceutical industry to make investigational drugs available for the treatment of serious or life-threatening diseases. Adefovir dipivoxil is an investigational, once-daily, reverse transcriptase inhibitor being studied in combination with other antiretroviral agents in late-stage Phase III clinical trials for the treatment of HIV infection.
"With more than 7,800 patients enrolled in our U.S. expanded access program for adefovir dipivoxil, there is strong evidence that patients need new antiviral treatments, particularly those that remain active against resistant viral strains," said John C. Martin, President and Chief Executive Officer of Gilead Sciences. "By broadening this program internationally, we hope to provide greater access to adefovir dipivoxil and its unique resistance profile prior to commercial availability."
Program Design
The design of the international expanded access program mirrors Gilead's ongoing U.S. initiative and incorporates input from physicians, regulatory agencies and representatives of the HIV/AIDS patient community. The program will make adefovir dipivoxil available free of charge to HIV-positive patients at least 13 years of age who have failed treatment with at least two nucleoside analog reverse transcriptase inhibitors and one protease inhibitor, regardless of their HIV RNA plasma level or CD4 cell count. Patients will receive a once daily dose of adefovir dipivoxil 60 mg and the nutritional supplement L-carnitine. In addition to adefovir dipivoxil, Gilead advises physicians caring for patients in the expanded access program to add to their patients' regimens at least one new antiretroviral agent that has not been previously administered.
Gilead will administer the international components of the adefovir dipivoxil expanded access program with support from divisions of NeXstar Pharmaceuticals. NeXstar is facilitating drug distribution from the United States to physician sites in France and will provide support as needed throughout Europe and Australia. On March 1, 1999, Gilead and NeXstar announced a definitive merger agreement by which Gilead would acquire NeXstar in a tax-free, stock-for-stock transaction. The transaction is subject to approval of the Securities and Exchange Commission and the stockholders of both companies.
In addition to France and Canada, Gilead is planning to file regulatory applications to make adefovir dipivoxil available through expanded access programs in countries throughout Europe and Australia. Quintiles will serve as the contract research organization for the expanded access program in Europe and Australia, and Kern McNeill International (KMI) will administer the Canadian program.
New Drug Application
In November 1998, the U.S. Food and Drug Administration granted Fast Track designation to adefovir dipivoxil for HIV, which provides for agency review of the New Drug Application (NDA) within six months from the date of final submission. Gilead initiated a rolling NDA submission in January 1999 by filing the Chemistry, Manufacturing and Controls section of the application. In the second quarter of this year, Gilead intends to complete the NDA submission for the accelerated approval of adefovir dipivoxil 60 mg for the treatment of HIV-infected patients with clinical, immunologic or virologic progression despite prior reverse transcriptase inhibitor therapy. Regulatory filings will follow under the centralized procedure in the European Union, where the review process generally requires at least 12 months.
Ongoing Clinical Program
In addition to the ongoing dose comparison trial (Study 417) to evaluate the relative safety and efficacy of the 60 mg and 120 mg doses of adefovir dipivoxil and the trial to evaluate use of the compound in treatment-naive patients (Study 411), Gilead also has initiated several new confirmatory studies of the compound in the United States, Europe, Canada and Australia. These trials are designed to further characterize the long-term efficacy and safety of adefovir dipivoxil 60 mg, explore emerging HIV treatment strategies and satisfy traditional regulatory guidelines for drug approval.
-- Intensification. Study 415 is a multinational, 48-week study designed to evaluate the safety and efficacy of adefovir dipivoxil 60 mg compared to placebo when added to highly active antiretroviral therapy in patients with HIV RNA less than 400 but greater than 50 copies/mL. This confirmatory trial is beginning to enroll patients in the United States, the United Kingdom, France, Germany and Canada.
-- Protease-Sparing Regimens. Study 432 is a 48-week, open-label trial designed to evaluate the safety and efficacy of adefovir dipivoxil 60 mg once daily as part of a protease-sparing treatment strategy. In this study, a regimen combining adefovir dipivoxil, efavirenz (EFV) and lamivudine (3TC) will be compared to EFV, 3TC and stavudine (d4T) in treatment-naive patients.
The study is enrolling patients in the United Kingdom, France, Germany and Australia.
-- Simplified Regimens. Study 434 is a 24-week Canadian trial currently enrolling patients to evaluate the anti-HIV effect of a standard triple drug regimen of indinavir (IDV), lamivudine (3TC) plus zidovudine (ZDV) or stavudine (d4T) compared to a simplified once-daily regimen including adefovir dipivoxil 60 mg, didanosine (ddI), 3TC and nevirapine (NVP).
-- Treatment-Experienced Patients. Study 458 is a 48-week multinational trial designed to evaluate the safety and efficacy of adefovir dipivoxil 60 mg once daily as part of combination therapy for patients who have failed prior treatment with nucleoside reverse transcriptase inhibitors. This confirmatory trial is planned to begin during the second half of this year.
Physician Registration
Physicians who wish to request registration materials and more information about the adefovir dipivoxil expanded access program or ongoing clinical trials may call 1-800-GILEAD-5 (toll-free in the U.S.) or 1-650-522-5850 (from outside the U.S.). For specific information about the expanded access program in Europe and Australia, physicians may call the Quintiles European office directly at 33-3-88-77-45-98. Information about clinical trial locations also may be found by using the Clinical Trial Locator on the Gilead Web site at www.gilead.com.
Safety Profile
During clinical testing, the most common side effects reported with adefovir dipivoxil for HIV have been dose-related gastrointestinal effects, including nausea and loss of appetite. Nephrotoxicity, including changes in serum creatinine and phosphate, is the most important drug-related toxicity. These changes in renal function are generally gradual in onset, asymptomatic, detectable by routine laboratory monitoring and resolvable upon dose reduction or withdrawal. Elevations in liver transaminases have been observed in some patients.
Gilead Sciences
Gilead Sciences is an independent biopharmaceutical company that seeks to provide accelerated treatment solutions for patients and the people who care for them. The company discovers, develops and commercializes proprietary therapeutics for important viral diseases, including a currently marketed product, VISTIDE (cidofovir injection), for the treatment of CMV retinitis, a sight-threatening viral infection in patients with AIDS. In addition, the company is developing products to treat diseases caused by HIV, hepatitis B virus and influenza virus.
This press release contains forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, concerning the timing and nature of potential registration filings for adefovir dipivoxil for HIV and presentation of clinical data at scientific conferences. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective as human therapeutics. Actual results could differ materially from those projected in this release. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Annual Report on Form 10-K for the year ended December 31, 1998 on file with the U.S. Securities and Exchange Commission, copies of which are available from Gilead.
Note to Editors: PREVEON and VISTIDE are registered trademarks of Gilead Sciences, Inc.
To receive more information, please visit the Gilead Web site at www.gilead.com or call Corporate Communications at 1-800-GILEAD-5 (1-800-445-3235)
Contact: Gilead Sciences Susan Hubbard, 650/522-5715 (Investors) Sheryl Meredith, 650/522-5505 (Media)
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