Gilead Announces 24-Week Results from Phase II Study of Investigational HIV Integrase Inhibitor GS 9137
- Category: Small Molecules
- Published on Monday, 05 March 2007 02:00
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LOS ANGELES, CA, USA | Mar 01, 2007 | Gilead Sciences, Inc. (Nasdaq:GILD) today announced 24-week data from a Phase II clinical trial evaluating three doses of GS 9137 (elvitegravir), a novel oral HIV integrase inhibitor. The data, presented this week at the 14th Conference on Retroviruses and Opportunistic Infections (CROI) by Andrew Zolopa, MD, Associate Professor, Stanford School of Medicine (Abstract #J-1007, Late Breaker #143LB), show statistically superior reductions in viral load among HIV-positive treatment-experienced patients receiving 125 mg of once-daily GS 9137 boosted with 100 mg of ritonavir, compared to those receiving a boosted protease inhibitor, both in combination with an optimized background regimen.
"Integrase inhibitors represent a promising new class in the field of HIV treatment, and I am encouraged by these Phase II data for once-daily GS 9137," said Dr. Zolopa. "As a clinician, I am frequently reminded of the importance of expanding simplified treatment options for people living with HIV, particularly among treatment-experienced patients who have developed resistance to many existing medications."
Integrase inhibitors are an investigational class of antiretrovirals that interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. Novel classes of HIV-fighting drugs are needed as patients live longer and exhaust currently available treatment options.
About the Study
This ongoing Phase II study is a partially-blinded, randomized, active-controlled, 48-week clinical trial to evaluate the non-inferiority of once-daily GS 9137 versus boosted comparator protease inhibitors (CPI/r) in HIV-infected treatment-experienced patients. Two hundred and seventy-eight (278) patients were randomized and received either once-daily GS 9137 20 mg (n=71), 50 mg (n=71) or 125 mg (n=73), each with 100 mg of ritonavir, or CPI/r (n=63), all in combination with an optimized background regimen of two or more nucleoside reverse transcriptase inhibitors (NRTIs) with or without the fusion inhibitor T-20. Patients receiving T-20 as part of their background regimen were stratified across treatment arms. At study entry, patients were required to have HIV RNA (viral load) of at least 1,000 copies/mL and at least one protease resistance mutation. There was no CD4 cell count entry criterion for study participants.
At baseline, study participants had a mean viral load of 4.59 log10 copies/mL, a mean CD4 cell count of 185 cells/mm3 and HIV isolated from patients exhibited a median of 11 protease resistance mutations. The independent data safety monitoring board reviewed week eight data and based on its recommendation, the GS 9137 20 mg arm was closed due to a high rate of virologic failure. Patients in this arm of the study were offered open-label GS 9137 125 mg. The addition of darunavir or tipranavir to the GS 9137 study arms was also permitted at week eight following the availability of data demonstrating a lack of drug interactions between both protease inhibitors and GS 9137. These interaction data were unavailable at the initiation of the study, precluding the use of protease inhibitors in the optimized background regimen in the GS 9137 arms at study entry. Prior to week 24, 15 percent of patients in the GS 9137 50 and 125 mg arms of the study added either darunavir or tipranavir and 37 percent of patients in the CPI/r arm who met protocol-defined criteria for virologic failure were switched to open-label GS 9137.
Rapid and potent antiviral activity was observed in the 50 and 125 mg GS 9137 arms of the study. The primary endpoint of the study was DAVG24, a measure of viral load reduction over 24 weeks. The mean DAVG24 for patients receiving 50 mg of once-daily boosted GS 9137 was -1.4 log10 copies/mL versus -1.2 log10 copies/mL for the comparator arm (95% confidence interval, -0.6, 0.2; p=0.27). The mean DAVG24 for patients receiving 125 mg of once-daily boosted GS 9137 was -1.7 log10 copies/mL versus -1.2 log10 copies/mL for the comparator arm (95% confidence interval, -0.8, -0.05; p=0.02).
Among patients who received GS 9137 125 mg, the durability of antiviral response was related to having active agents in the optimized background regimen. In the GS 9137 125 mg arm, patients receiving T-20 for the first time, or those who had at least one active NRTI in their background regimen (n=47), experienced significantly greater mean reductions in viral load at 24 weeks compared to those with no active NRTIs and no first use of T-20 (n=26; -2.1 log10 copies/mL versus -0.7 log10 copies/mL, respectively; p less than 0.001). Active agents were determined using Genotypic Susceptibility Scores (GSS), a measure of viral susceptibility to an antiretroviral agent.
At 16 weeks, 38 percent (27/71) of patients in GS 9137 50 mg arm and 40 percent (29/73) of patients in the GS 9137 125 mg arm achieved HIV RNA less than 50 copies/mL compared to 30 percent (19/63) of patients in the CPI/r arm of the study, using an intent to treat analysis where missing equals failure. At 24 weeks, 32 percent (23/71) of patients in the GS 9137 50 mg arm and 36 percent (26/73) of patients in the GS 9137 125 mg arm achieved HIV RNA less than 50 copies/mL compared to 27 percent (17/63) of patients in the CPI/r arm. At 16 weeks, mean increases in CD4 cell count among patients receiving 50 mg and 125 mg of GS 9137 were 52 and 61 cells/mm3 versus 28 cells/mm3 for the comparator arm. At 24 weeks, the increase in CD4 cells was also similar across the arms (53 and 57 versus 53 cells/mm3, respectively). These differences were not statistically significant.
GS 9137 was well tolerated. No dose relationship was observed in treatment-emergent Grade 3 or 4 adverse events, laboratory abnormalities or discontinuations of study drug, and incidences of events across these safety and tolerability parameters were similar between the GS 9137 and CPI/r arms of the study.
"We are very encouraged by the rapid and potent antiviral activity observed with the 125 mg dose of GS 9137, particularly in this heavily treatment-experienced population," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development, Gilead Sciences. "We are currently in the process of reviewing the full data set from this study with the FDA, along with plans for registrational studies."
About GS 9137
GS 9137, also known as JTK-303, was licensed by Gilead from Japan Tobacco Inc. (JT) in March 2005. Under the terms of the company's agreement with JT, Gilead has exclusive rights to develop and commercialize GS 9137 in all countries of the world, excluding Japan where JT retains rights. As an investigational compound, GS 9137 has not yet been determined safe or efficacious in humans for its ultimate intended use.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, 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 risks related to Gilead's ability to successfully develop and commercialize GS 9137. For example, the safety and efficacy data from additional clinical studies may not warrant further development of this compound, and initiating and completing clinical trials may take longer or cost more than expected. Future discussions with the FDA may impact the amount of data needed and timelines for review, and Gilead's clinical trial protocol design, clinical endpoint and statistical analyses for any additional trials will be subject to FDA review and approval. In addition, integrase inhibitors represent a relatively new class of compounds that has not had a long history of clinical research and development. Therefore, Gilead may face challenges in clinical trial protocol design and trial enrollment, and the results of clinical trials involving integrase inhibitors may be less predictable than with other drug candidates for the treatment of HIV. 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's Annual Report on Form 10-K for the year ended December 31, 2005 and Reports on Form 10-Q for the first three quarters of 2006, filed 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.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
CONTACT: Gilead Sciences, Inc.
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SOURCE: Gilead Sciences, Inc.