Gilead Sciences, Inc. (Nasdaq: GILD) today announced two-year Phase 3 clinical trial results showing that the integrase inhibitor elvitegravir dosed once daily is non-inferior to raltegravir dosed twice daily among treatment-experienced HIV patients. These findings will be presented today in an oral session (abstract #TUAB0105) at the 19th International AIDS Conference (AIDS 2012) in Washington, D.C. “As patients are living with HIV longer, there is a continued need for new treatment options – particularly those that are effective against strains of the virus that have developed resistance to currently available therapies,” said Richard Elion, MD, Clinical Research Director, Whitman-Walker Health, and principal investigator of the study. “In this study, elvitegravir demonstrated similar efficacy and tolerability as raltegravir among a difficult-to-treat patient population.” In the trial (Study 145), patients received elvitegravir or raltegravir, each with a background regimen that included a ritonavir-boosted protease inhibitor and another antiretroviral. At 96 weeks of treatment, 48 percent of elvitegravir patients compared to 45 percent of raltegravir patients achieved and maintained HIV RNA (viral load) levels less than 50 copies/mL, based on the U.S. Food and Drug Administration (FDA) Time to Loss of Virologic Response (TLOVR) algorithm (Intent-to-Treat (ITT) population; 95 percent CI for the difference: -4.6 percent to +9.9 percent; predefined criterion for non-inferiority was the lower bound of a two -sided 95 percent CI of -10 percent). Rates of adverse events, discontinuations due to adverse events and development of resistance were similar for elvitegravir and raltegravir, though Grade 2-4 diarrhea was more frequent among elvitegravir patients (13 percent) than raltegravir patients (8 percent) (p=0.02). On June 27, 2012, Gilead submitted a marketing application to FDA for elvitegravir. Elvitegravir is also under regulatory review by the European Medicines Agency. Topline 96-week results from Study 145 were announced on December 9, 2011. About Study 145 Study 145 is a randomized (1:1), double-blind, double-dummy, active-controlled Phase 3 clinical trial comparing the efficacy and safety of elvitegravir (n=354) versus raltegravir (n=358), each administered with a ritonavir-boosted background regimen. Eligible participants were HIV-infected treatment-experienced patients with HIV RNA (viral load) of greater than or equal to 1,000 copies/mL and were required to have documented viral resistance and/or at least six months of treatment experience with two or more different classes of antiretrovirals prior to enrollment.
Trial participants received either once-daily elvitegravir (150 mg or 85 mg) or twice-daily raltegravir (400 mg). Patients’ background regimens were based on the results of resistance testing and included a fully-active ritonavir-boosted protease inhibitor, and a second agent that was permitted to be a nucleoside or nucleotide reverse transcriptase inhibitor, etravirine, maraviroc or enfuvirtide. Due to known pharmacokinetic interactions, patients randomized to elvitegravir whose background protease inhibitor was either atazanavir or lopinavir received an 85 mg dose of elvitegravir.In January 2011, Gilead announced that it would extend the blinded, randomized period of Study 145 from the originally planned 48 weeks to 96 weeks in order to obtain longer-term safety and efficacy data. Based on the achievement of the non-inferiority endpoint at 48 weeks, patients continued to receive the regimen to which they were originally randomized in a blinded fashion through 96 weeks. Secondary endpoints included additional measures of the efficacy, safety and tolerability of the two treatment regimens. At baseline, the median HIV RNA in the elvitegravir and raltegravir arms, respectively, was 4.35 log 10 copies/mL and 4.42 log 10 copies/mL. Median CD4 cell counts were 227 cells/mm 3 and 215 cells/mm 3 for the elvitegravir and raltegravir arms, respectively. Mean increases in CD4 cell counts at Week 96 were 205 cells/mm 3 for elvitegravir patients and 198 cells/mm 3 for raltegravir patients. Virologic failure rates were similar in both arms: 26 percent for elvitegravir patients and 29 percent for raltegravir patients. Of those patients randomized, 7 percent of patients in each arm developed an integrase resistance mutation. The most common Grade 2-4 adverse events occurring in greater than or equal to 5 percent of patients in either treatment arm were diarrhea, back pain, depression, bronchitis, upper respiratory tract infection, sinusitis, arthralgia and urinary tract infection. The incidence of these adverse events was similar in both treatment arms with the exception of diarrhea, which was more common in the elvitegravir arm (p=0.02).
Three percent and 4 percent of elvitegravir and raltegravir patients, respectively, discontinued treatment due to adverse events. The frequency of serious adverse events was similar in both arms. The most common serious adverse events occurring in three or more patients in either group were pneumonia, cellulitis, suicidal ideation, dyspnea, bronchitis, chest pain and hepatitis.Laboratory abnormalities (Grade 3-4) occurring in greater than or equal to 5 percent of patients in either treatment arm were total bilirubin, AST, ALT, GGT, amylase, creatine kinase, total cholesterol and hematuria. The frequency of laboratory abnormalities was also similar in both treatment arms with the exception of Grade 3-4 liver abnormalities, which were higher among patients taking raltegravir (7 percent GGT; 5 percent ALT; 6 percent AST) as compared to elvitegravir (3 percent GGT; 2 percent ALT; 2 percent AST) with p-values less than or equal to 0.05 for all liver tests. Additional information about the study can be found at www.clinicaltrials.gov. About Elvitegravir Integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. Elvitegravir was licensed by Gilead from Japan Tobacco Inc. (JT) in March 2005. Under the terms of Gilead's agreement with JT, Gilead has exclusive rights to develop and commercialize elvitegravir in all countries of the world, excluding Japan, where JT retains rights. Elvitegravir is also a component of the Quad single tablet regimen. About Quad The Quad contains elvitegravir, cobicistat (a pharmacoenhancing or “boosting” agent that enables once-daily dosing of elvitegravir), and Truvada ® (emtricitabine and tenofovir disoproxil fumarate). In October 2011, Gilead submitted a New Drug Application to FDA for the Quad for the treatment of HIV. FDA has set a target action date for the Quad under the Prescription Drug User Fee Act (PDUFA) of August 27, 2012. Elvitegravir, cobicistat and the Quad are investigational products and have not yet been determined safe or efficacious in humans.
About Gilead SciencesGilead 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 Asia Pacific. Forward-Looking Statement 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 Gilead may fail to obtain approvals for elvitegravir or Quad from regulatory authorities and any marketing approvals, if granted, may have significant limitations on their use. As a result, elvitegravir and Quad may never be successfully commercialized. In addition, Gilead may make a strategic decision to discontinue development of elvitegravir or Quad if, for example, it believes commercialization will be difficult relative to other opportunities in its pipeline. 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 Gilead's Quarterly Report on Form 10-Q for the quarter ended March 31, 2012, as 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. U.S. full prescribing information for Truvada is available at www.Truvada.com . Truvada is a registered trademark of Gilead Sciences, Inc. For more information on Gilead Sciences, please visit the company’s website at www.gilead.com , follow Gilead on Twitter ( @GileadSciences ) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.