AASLD:GS 9190 and GS 9256 in Combination with Standard of Care Therapies Achieve Substantial Viral Suppression in Phase II Study

press release
Oct. 30, 2010, 9:00 a.m. EDT
Gilead's Investigational Hepatitis C Compounds GS 9190 and GS 9256 in Combination with Standard of Care Therapies Achieve Substantial Viral Suppression in Phase II Study
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-- Compounds Among the Company's Seven HCV Pipeline Candidates Spanning Six Therapeutic Classes --

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BOSTON, Oct 30, 2010 (BUSINESS WIRE) -- Gilead Sciences, Inc. /quotes/comstock/15*!gild/quotes/nls/gild (GILD 39.67, -0.19, -0.48%) today announced data from a Phase IIa study showing that its investigational compounds GS 9190 and GS 9256, used in conjunction with current standard of care therapies, produced substantial suppression of the hepatitis C virus (HCV) within 28 days of treatment. The findings are being presented Monday, November 1, during a latebreaker oral session (#LB-1) at the 61st annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2010) in Boston.

"Patients with chronic hepatitis C urgently need new and better treatment options, particularly combination therapies involving antiviral drugs that employ multiple mechanisms of action to eradicate the virus," said the study's principal investigator, Stefan Zeuzem, MD, JW Goethe University Hospital, Frankfurt, Germany. "The data presented today support the continued clinical evaluation of GS 9190 and GS 9256 in combination with other hepatitis C therapies and provide additional clinical insight into the effect of ribavirin in the absence of interferon."

More than seven million people in industrialized countries are chronically infected with HCV, and as many as three million Americans have the disease. The current standard of care in HCV therapy is the oral antiviral ribavirin (RBV), administered in combination with peg-interferon (Peg-IFN), which is delivered via injection and achieves a sustained therapeutic response in only 40-55 percent of patients with HCV genotype 1, the most common form of HCV in the Americas and Europe.(1)

Gilead's three-arm Phase IIa trial (Study 196-0112) evaluated the safety and efficacy of GS 9190, an oral polymerase inhibitor, in combination with GS 9256, an oral protease inhibitor, when used as: 1) a dual antiviral therapy alone; 2) a three-drug regimen with RBV; or 3) a four-drug regimen with RBV and Peg-IFN. The study found that the all-oral regimen of GS 9190, GS 9256 and RBV produced substantial viral suppression, with a median maximal decline from baseline in HCV RNA of 5.1 log10 IU/mL during 28 days of treatment. Among patients given the four-drug regimen of GS 9190, GS 9256, RBV and Peg-IFN, 100 percent (14/14 patients) achieved Rapid Virologic Response (RVR) (HCV RNA < 25 IU/mL) at day 28, with 93 percent (13/14 patients) achieving undetectable viral levels (HCV RNA < 10 IU/mL). No virologic breakthroughs were observed in this arm. "Oral combinations of multiple antiviral agents are expected to become the new standard of care for patients with hepatitis C, and our ultimate goal and vision is to develop a potent and well-tolerated fixed-dose combination product that will eliminate the need for peg-interferon," said John McHutchison, MD, Senior Vice President for Liver Disease Therapeutics at Gilead. "These data strongly support the clinical potential of this oral combination HCV therapy, and we're looking forward to advancing the development of GS 9190 and GS 9256." About Study 196-0112 This Phase IIa, randomized, open-label trial is evaluating GS 9190 and GS 9256 in combination (n=16), and with RBV (n=15) or with RBV/Peg-IFN (n=15). The trial enrolled treatment-naive adults with chronic HCV genotype 1 for a 28-day course of treatment. The primary outcome measures of the trial are the percentage of subjects achieving RVR, defined as HCV RNA < 25 IU/mL at Day 28, as well as the incidence of treatment-related side effects and adverse events. Patients in the two-drug arm of the study received GS 9190 (40 mg twice daily) and GS 9256 (75 mg twice daily). Patients in the three-drug arm received a regimen of GS 9190, GS 9256 and RBV (1,000-1,200 mg total daily dose, administered twice daily), and patients in the four-drug arm also received Peg-IFN (180 g, injected once per week). In the final analysis, one patient in the four-drug arm was excluded due to a protocol violation. A median maximal decline from baseline HCV RNA of 4.1 log10 IU/mL was observed in patients receiving the two-drug combination of GS 9190 and GS 9256. The addition of RBV and RBV/Peg-IFN enhanced these responses, with median maximal RNA declines of 5.1 log10 IU/mL and 5.7 log10 IU/mL, respectively. GS 9190 and GS 9256 were generally well tolerated. The majority of adverse events were Grade 1 or 2 in severity and resolved with continued treatment. The most common adverse events observed in each of the three arms were headache, diarrhea and nausea. Some patients taking the three-drug combination also experienced fatigue and insomnia, and some patients taking the four-drug combination experienced influenza-like illness, fatigue, myalgia and cough. There were two serious adverse events including one case of bursitis and a hospitalization for vasovagal collapse (fainting), which was attributed to gastroenteritis and occurred in a patient who continued therapy and achieved RVR. Elevations in bilirubin were observed across all three study arms, the majority of which were Grade 1 or 2 in severity and none of which resulted in study drug discontinuation. Additional Gilead HCV Pipeline Research In addition to Study 196-0112, data from seven additional studies will be presented at The Liver Meeting highlighting the clinical profile of the company's other HCV pipeline candidates, including another protease inhibitor, GS 9451, and a novel NS5A inhibitor, GS 5885. Gilead's HCV pipeline now includes seven unique molecules spanning six therapeutic classes with different mechanisms of action. Five of these compounds are currently in clinical trials, and two are slated to enter human clinical studies early next year. In a Phase I three-day dose-ranging study (Study 169-0103), GS 9451 was found to be highly potent in terms of anti-HCV activity and demonstrated a long plasma half-life with once-daily dosing potential (Abstract #820). GS 9451 was tested among 33 patients with HCV genotype 1a (GT1a) or 1b (GT1b). GT1a patients received GS 9451 at 60 mg, 200 mg and 400 mg once-daily doses, and the median maximal decline from baseline in HCV RNA was 0.88, 3.2 and 3.6 log10 IU/mL, respectively. GT1b patients received GS 9451 at a 200 mg once-daily dose, and the median maximal reduction was 3.5 log10 IU/mL. The median half-life of GS 9451 at these doses ranged from 14 to 17 hours, which will allow for once-daily dosing. Treatment-emergent adverse events were generally mild to moderate. Adverse events occurring in at least two patients at any dose were headache (n=7) and dyspepsia (n=2). Gilead also presented the first Phase I data on a novel NS5A inhibitor for HCV (Study 256-0101), GS 5885, which suggest that this compound also has once-daily dosing potential (Abstract #1883). In preclinical studies, GS 5885 demonstrated low picomolar potency and a favorable safety and pharmacokinetic profile. The clinical safety profile of GS 5885 was assessed in an escalating, single oral dose trial in 54 healthy volunteers (randomized 8:2 to receive GS 5885 versus placebo). The compound was dosed under fasted conditions at 3 mg, 10 mg, 30 mg (under fasted and fed conditions), 60 mg and 100 mg, and was well tolerated, with no serious adverse events and no treatment-emergent grade 3/4 laboratory abnormalities for one week after a single dose. Adverse events were few and generally mild, and included headache, dizziness, myalgia, dysmenorrhea and contact dermatitis from electrocardiogram (ECG) leads. GS 5885 exposure was proportional over the dosing range and produced a mean terminal half-life of 37 to 45 hours, demonstrating potential for once-daily dosing. Based on the results of the studies presented at The Liver Meeting, Gilead is advancing its HCV pipeline with three new studies slated for initiation before the end of 2010. The first is a Phase IIb clinical trial of GS 9190 and GS 9256 administered with the current standard of care, evaluating the potential to reduce the required duration of HCV therapy (including RBV/Peg-IFN) from 48 to 16 weeks. Similarly, a second Phase IIb trial will assess GS 9190 plus GS 9451 and the current standard of care. Finally, Gilead will be initiating a drug interaction study of GS 5885 in preparation for a Phase IIb study of GS 5885 plus a protease inhibitor and the current standard of care. GS 9190, GS 9256, GS 9451 and GS 5885 are investigational products and have not yet been determined safe or efficacious in humans. 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. Forward-Looking Statement This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, which are subject to risks, uncertainties and other factors, including the risks related to Gilead's ability to complete Phase II clinical trials of GS 9190 and GS 9256 in a timely matter or at all. There may be unfavorable results in ongoing or any further clinical trials of GS 9190, GS 9256, GS 9451 and GS 5885, and Gilead may need to modify, delay or terminate such clinical trials. Gilead may ultimately be unable to obtain FDA and other regulatory approvals, and as a result, GS 9190 and GS 9256 may never be successfully commercialized. In addition, Gilead may choose to advance alternative candidates in its HCV pipeline based on the emerging profile of these compounds in clinical trials. 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 first and second quarters of 2010, 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. 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. (1) National Institutes of Health. Chronic Hepatitis C: Current Disease Management. November 2006. SOURCE: Gilead Sciences, Inc. Gilead Sciences, Inc. Susan Hubbard, 650-522-5715 (Investors) Cara Miller, 650-522-1616 (Media) Copyright Business Wire 2010