June 13, 2003
96-Week Data from Gilead's Study 903 Show Low Rate of Virologic Failure among Patients Taking Viread
LOS CABOS, Mexico--(BUSINESS WIRE)--June 13, 2003--Gilead Sciences, Inc. (Nasdaq:GILD) today announced 96-week data from an ongoing clinical trial demonstrating that resistance to Viread(R) (tenofovir disoproxil fumarate) among treatment-naive patients occurs infrequently. These findings are consistent with data from Gilead's studies in treatment-experienced patients. The data were presented today (Abstract #135) by Michael Miller, PhD, Director of Clinical Virology at Gilead Sciences, at the 12th International HIV Drug Resistance Workshop in Los Cabos, Mexico.
The data are from Study 903, an ongoing three-year randomized, double-blind trial, which is being conducted in the United States, Europe and South America. The study was designed to compare the efficacy and safety of a treatment regimen of Viread, lamivudine (3TC) and efavirenz to a regimen of stavudine (d4T), lamivudine and efavirenz in 600 antiretroviral-naive HIV-1 infected patients. In addition, patients with evidence of efficacy failure had their HIV genotyped and phenotyped to characterize the development of resistance mutations.
"These 96-week resistance data confirm the favorable resistance profile of the Viread regimen evaluated in this study," explained Dr. Miller. "Less than three percent of patients developed a Viread-associated mutation. While these patients did experience low-level changes in Viread susceptibility, their long-term treatment options, including remaining on Viread, were not significantly limited and their physicians were able to design successful second-line regimens."
In vitro and earlier clinical trials show that Viread infrequently selects for the K65R mutation, a reverse transcriptase mutation. In this 96-week analysis, virologic failure developed in approximately 12 percent of all patients (74/600), with no statistically significant difference between the two treatment arms. Resistance to efavirenz and 3TC were observed most frequently (6.5 and 4.5 percent, respectively) and without a significant difference between study arms. Through 48 weeks, the K65R mutation developed in seven Viread-treated patients (2.3 percent) versus two patients (0.7 percent) in the d4T arm. From week 48 through week 96, the K65R mutation developed in one additional Viread-treated patient resulting in a total of 2.7 percent of patients through 96 weeks versus 0.7 percent in the d4T arm. Development of efavirenz resistance either preceded or accompanied development of K65R in all cases.
Among the eight Viread-treated patients who developed K65R, there were only low-level changes in susceptibility to Viread and all were within the 4 fold cut-off that is associated with reduced clinical response to Viread. The K65R virus from these patients showed increased susceptibility for zidovudine (AZT), low-level changes for other nucleoside reverse transcriptase inhibitors (NRTIs) and decreased replication capacity in vitro. The patients who did not develop K65R showed no changes in susceptibility to Viread.
All eight Viread-treated patients who developed K65R began a new treatment regimen with a protease inhibitor and other NRTIs. Five of these eight patients, two of whom remained on Viread, achieved HIV RNA less than 50 copies/mL and no cases of virologic failure have been observed (median follow-up 76 weeks), two patients were without follow-up and one patient was non-adherent.
"These results underscore that, even after two years, treatment with Viread infrequently results in the development of resistance in treatment-naive patients," said John C. Martin, PhD, President and Chief Executive Officer, Gilead Sciences. "Resistance to antiretroviral therapies has emerged as a significant issue in the field of HIV. Viread's unique resistance profile provides physicians and their patients with an efficacious and reliable tool for the durable treatment of AIDS."
Gilead designed Study 903 as a three-year trial to gather a wide variety of data on Viread's efficacy and safety profile in a controlled manner over time. Study 903 is being conducted in the United States, Europe and South America. Twenty-six percent of the study participants are women, and 36 percent are people of color. According to the U.S. Centers for Disease Control, women now account for 30 percent of new HIV infections in the United States, while nearly three-fourths of new HIV infections affect non-Caucasians.
Viread is the first nucleotide analogue reverse transcriptase inhibitor (NtRTI) approved for the treatment of HIV in the United States and Europe. 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 110,000 patients have been prescribed Viread as part of their combination regimen. 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 with a meal.
Assessment of adverse reactions is based on two studies (902 and 907) in which 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. Adverse event rates in the Viread group were similar to those in the placebo-treated patients. The most common adverse events in these patients were mild to moderate gastrointestinal events, such as nausea, diarrhea, vomiting and flatulence. Laboratory abnormalities observed in clinical studies occurred with similar frequency in the Viread and placebo-treated groups.
In clinical practice, a number of adverse events, including renal impairment, nausea, rash and asthenia (weakness) have been reported. Renal impairment occurred most often in patients with underlying systemic or renal disease, or in patients taking concomitant nephrotoxic agents. 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.
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 six 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 a higher rate of resistance to Viread may occur following longer periods of treatment. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other 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.
Note to Editors: 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. Susan Hubbard, 650/522-5715 (Investors) Erin Edgley, 650/522-5635 (Media) SOURCE: Gilead Sciences, Inc.