October 28, 2003
New Data Highlight Safety and Tolerability Profile of Gilead's Viread for Periods up to Four Years; Data Presented at European AIDS Conference in Warsaw
WARSAW, Poland--(BUSINESS WIRE)--Oct. 28, 2003--Gilead Sciences, Inc. (Nasdaq:GILD) today announced data from two studies evaluating the safety and tolerability of its once-daily antiretroviral agent Viread(R) (tenofovir disoproxil fumarate). These data will be presented this week at the 9th Conference of the European AIDS Clinical Society in Warsaw, Poland.
The first presentation (Abstract 7.3/7) describes data from Study 910, an extension of two pivotal clinical studies of Viread in which treatment-experienced HIV patients received Viread for periods of up to four years. Results show that Viread was associated with a low incidence and severity of adverse events and laboratory abnormalities.
The second presentation (Abstract F8/5) highlights results from the RECOVER study in which 1350 highly treatment-experienced patients substituted Viread for a drug from their existing antiretroviral treatment regimen. Results suggest that the use of Viread may improve dyslipidemia associated with stavudine-based regimens, while maintaining viral suppression.
"Physicians and patients need therapeutic choices that will help to maximize the potential for long-term treatment success," said John Martin, PhD, President and Chief Executive Officer of Gilead Sciences. "Efficacy against HIV is important, but for a drug to be a viable treatment option, it has to be well-tolerated and have a favorable long-term safety profile. These data allow us to better understand the profile of Viread and its utility in addressing many of the issues facing physicians and patients in the management of HIV disease."
Study 910 Results
This study was designed to evaluate the long-term safety profile of Viread in treatment-experienced patients. Study 910 is an extension of two pivotal studies of Viread (Studies 902 and 907) in which Viread was added in a randomized, double-blind, placebo-controlled manner to patients' existing antiretroviral regimens. At baseline, the mean duration of prior antiretroviral use for all patients was approximately five years. Patients received Viread 300 mg (n=443) or placebo (n=210) added to an existing standard antiretroviral therapy during the 24-week double-blind periods of the studies. Including crossovers from placebo to Viread, a total of 687 patients remained on study for a mean of 113 weeks, with a maximum time of 220 weeks.
During the initial 24 weeks, the severity and incidence of adverse events and laboratory abnormalities, as well as the incidence of discontinuations from study for adverse events, were similar (less than or equal to 3 percent) between the Viread and placebo groups. During the extended dosing periods of the studies, the adverse events and laboratory abnormalities remained similar to placebo after accounting for the increased duration of exposure (113 weeks vs. 24 weeks). Serum creatinine elevations and hypophosphatemia were generally sporadic, transient and resolved without interruption to treatment. No patient receiving Viread developed a grade two, three or four (greater than or equal to 2.1 mg/dL) serum creatinine elevation. The incidence of grade three and four hypophosphatemia (less than 1.5 mg/dL) remained similar (1 percent) to that of placebo group through 24 weeks.
RECOVER Study Results
Results from a second study suggest that the use of Viread may improve dyslipidemia associated with stavudine-based regimens, while maintaining viral suppression. This prospective, multi-center study was designed to evaluate the strategy of managing nucleoside reverse transcriptase inhibitor (NRTI) treatment-limiting toxicities by replacing the involved drug with Viread 300 mg in heavily treatment-experienced, virologically-suppressed HIV patients. Of 1350 patients, 65 percent switched from stavudine, 13 percent switched from didanosine, 13 percent switched from zidovudine, 6 percent switched from abacavir, 2 percent switched from lamivudine and 1 percent switched from zalcitabine.
At 12 weeks, data indicate that patients who switched from stavudine to Viread (n=94) because of stavudine-associated lipid side effects experienced rapid and significant decreases in triglyceride levels (a mean decrease of 179.61 mg/dL; p less than 0.001) after switching to Viread. Twenty percent of patients switching to Viread experienced a return to normal triglyceride levels. Mean cholesterol levels also decreased by 34.77 mg/dL after the switch (n=70; p less than 0.001), and no virological rebound was seen in patients who switched to Viread. The RECOVER Study is currently ongoing in 120 Spanish centers. Follow-up will be scheduled with all patients at 48 weeks.
"Physicians and patients are increasingly concerned about the long-term impact of antiretroviral therapy on triglyceride and cholesterol levels and avoiding serious side effects like cardiovascular problems and metabolic conditions such as lipodystrophy," said Pere Domingo, MD, Hospital de Sant Pau, Barcelona, Spain. "The study demonstrates that Viread is an important treatment alternative for doctors and patients with serious concerns about antiretroviral-related dyslipidemia."
In the United States and Europe, Viread is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts in controlled studies of Viread in treatment-naive and treatment-experienced adults. There are no study results demonstrating the effect of Viread on clinical progression of HIV. The use of Viread should be considered for treating adult patients with HIV strains that are expected to be susceptible to tenofovir as assessed by laboratory testing or treatment history.
Viread is the first nucleotide analogue reverse transcriptase inhibitor (NtRTI) approved for the treatment of HIV in the United States and Europe. The drug works by blocking reverse transcriptase, an enzyme involved in the replication of HIV. Viread is dosed as one tablet once daily taken orally. In clinical trials and expanded access programs, approximately 10,000 patients have been treated with Viread alone or in combination with other antiretroviral products for periods up to four years. To date, an estimated 150,000 patients have been prescribed Viread as part of their combination regimen.
Assessment of adverse reactions is based on two studies of treatment-experienced patients and one study of treatment-naive patients. In studies 902 and 907, a total of 653 treatment-experienced patients received treatment with Viread 300 mg (n=443) or placebo (n=210) for 24 weeks followed by extended treatment with the drug. In Study 903, a total of 600 patients received treatment Viread (n=299) or stavudine (n=301) in combination with lamivudine and efavirenz for 48 weeks.
The most common adverse events that occurred in patients receiving Viread with other antiretroviral agents in clinical trials were dizziness and mild to moderate gastrointestinal events, such as nausea, diarrhea, vomiting and flatulence. Adverse events and laboratory abnormalities observed in clinical studies occurred with similar frequency in the Viread and placebo or control groups.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals. Renal impairment has been associated with the use of Viread during post-approval surveillance. The majority of cases occurred in patients with underlying systemic or renal disease, or in patients taking concomitant nephrotoxic agents. Exacerbations of hepatitis B have been reported in patients co-infected with HIV and chronic hepatitis B after discontinuation of Viread.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics to advance the care of patients suffering from life-threatening diseases worldwide. The company has seven marketed products and focuses its research and clinical programs on anti-infectives. Headquartered in Foster City, CA, Gilead has operations in the United States, Europe and Australia.
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors including the risk that in a clinical setting or through longer treatment periods Gilead may not continue to observe the safety data observed in these studies. These risks and uncertainties could cause actual results to differ materially from those referred to in the forward-looking statements. Risks are described in detail in the Gilead Annual Report on Form 10-K for the year ended December 31, 2002 and in Gilead's Quarterly Reports on Form 10-Q, all of which are on file with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead and Gilead assumes no obligation to update any such forward-looking statements.
Viread is a registered trademark of Gilead Sciences, Inc. For complete prescribing information, please visit www.viread.com.
For more information on Gilead Sciences, please visit the company's web site at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
CONTACT: Gilead Sciences, Inc. Investors Susan Hubbard, 650-522-5715 Media Amy Flood, 650-522-5643 (U.S.) James Loduca, +44 77 85 312 353 (Warsaw/E.U.) www.gilead.com SOURCE: Gilead Sciences, Inc.