LONDON--Gilead Sciences, Inc. (Nasdaq: GILD) today announced data from two Phase 2 studies and a compassionate access study in which a regimen containing once-daily Sovaldi® (sofosbuvir) 400 mg was administered for the treatment of chronic hepatitis C virus (HCV) infection in patients with advanced liver disease. These data are being presented this week at the 49th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress 2014) in London.
The first study, Study GS-US-334-0125 (Oral #068), is an ongoing open-label Phase 2 clinical trial evaluating HCV patients with cirrhosis and portal hypertension, with or without decompensation, who were randomized 1:1 to an immediate treatment arm in which Sovaldi and ribavirin (RBV) was administered for 48 weeks (n=25) or to a deferred treatment arm in which this regimen was initiated after a 24-week observation period (n=25). Eighty percent of participants were treatment-experienced.
Of the 22 patients who completed 24 weeks of therapy, 95 percent (n=21/22) achieved virologic suppression on treatment. Additionally, patients taking Sovaldi-based therapy experienced trends in clinical and laboratory parameter improvements compared to patients in the observation arm. Sovaldi-based therapy was well tolerated in the study, and only one patient discontinued treatment due to an adverse event. The most common adverse events occurring in more than 25 percent of patients included nausea and pruritis. Patients in both arms of the study will be followed to determine their 12-week sustained virologic response rates (SVR12) after 48 weeks of Sovaldi-based therapy.
Study GS-US-334-0126 (Poster #1232), was a single-arm open-label Phase 2 trial in which patients with established recurrent HCV infection following liver transplantation received up to 24 weeks of therapy with Sovaldi plus RBV (escalating doses starting at 400 mg/day). The majority of patients had genotype 1-HCV infection (n=33/40) and 88 percent (n=35/40) were treatment-experienced.
Seventy percent (n=28/40) of patients in this study achieved SVR12. The most common adverse events occurring in more than 20 percent of patients were fatigue, headache, arthralgia (joint pain) and diarrhea. There were no deaths, graft losses or episodes of organ rejection among post-liver transplantation patients, and no drug-drug interactions were reported between Sovaldi and immunosuppressive agents.
A third, compassionate access study (Oral #62), evaluated Sovaldi therapy among 104 post-transplant patients with severe recurrent HCV, including fibrosing cholestatic hepatitis, who had exhausted all other treatment options and received pre-approval access to Sovaldi via Gilead's compassionate use program. Patients received up to 48 weeks of Sovaldi plus RBV, with some patients also receiving pegylated interferon (peg-IFN) (180 μg/week) at their physician's discretion. The majority of patients in the study experienced clinical improvements on treatment. Overall, 62 percent of patients achieved SVR12. Sovaldi-based therapy was well tolerated.
"The patients included in these analyses are historically among the most difficult to cure, and many have had no appropriate treatment options until now," said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. "These data demonstrate that Sovaldi-based oral therapy can improve outcomes, has a favorable safety profile and is well tolerated among hepatitis C patients with severe liver disease."
Additional information about Study GS-US-334-0125 and Study GS-US-334-0126 can be found at www.clinicaltrials.gov.
Sovaldi is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. Sovaldi is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication.
Sovaldi was approved in the United States on December 8, 2013 and in the European Union on January 17. In the United States, Sovaldi is approved for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen. Efficacy has been established in subjects with HCV genotype 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection. Treatment response varies based on baseline host and viral factors. Monotherapy is not recommended for treatment of chronic hepatitis C. Studies GS-US-334-0125 and GS-US-334-0126 evaluated investigational uses of Sovaldi, for which safety and efficacy have not yet been established.
IMPORTANT SAFETY INFORMATION
Sovaldi combination treatment with ribavirin or with peginterferon alfa plus ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risk for birth defects and fetal death associated with ribavirin. Contraindications to peginterferon alfa and ribavirin also apply to Sovaldi combination treatment. Refer to the prescribing information of peginterferon alfa and ribavirin for a list of their contraindications.
Warnings and Precautions
- Pregnancy: Use with Ribavirin or Peginterferon Alfa/Ribavirin: Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Female patients of childbearing potential and their male partners must use two forms of non-hormonal contraception during treatment and for at least 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. Refer to the prescribing information for ribavirin.
- Use with Potent P-gp Inducers: Rifampin and St. John's wort should not be used with Sovaldi as they may significantly decrease sofosbuvir plasma concentration, reducing its therapeutic effect.
Most common (≥20 percent, all grades) adverse reactions for:
- Sovaldi + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia, and anemia
- Sovaldi + ribavirin combination therapy were fatigue, and headache
In addition to rifampin and St. John's wort, coadministration of Sovaldi is not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of sofosbuvir, reducing its therapeutic effect.
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 and South America, Europe and Asia Pacific.
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 possibility of unfavorable longer-term results from clinical trials evaluating Sovaldi for the treatment of HCV among patients with advanced liver disease, and the risk that healthcare providers, payers or insurers may not recognize the benefits of Sovaldi over other agents. As Sovaldi is used over longer periods of time by treatment-experienced patients with underlying health problems taking numerous other medicines, Gilead may find new issues such as safety, resistance or drug interaction issues, which may require it to provide additional warnings or contraindications in the label, which could reduce the market acceptance of Sovaldi. 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 Annual Report on Form 10-K for the year ended December 31, 2013, 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 Sovaldi is available at www.gilead.com.
Sovaldi is a registered trademark of Gilead Sciences, Inc.
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