Japan's Ministry of Health, Labour and Welfare Approves Gilead's Harvoni®, the First Once-Daily Single Tablet Regimen for the Treatment of Genotype 1 Chronic Hepatitis C

FOSTER CITY, Calif.--(BUSINESS WIRE)--Jul. 3, 2015-- Gilead Sciences, Inc. (NASDAQ:GILD) today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg), the first once-daily single tablet regimen for the treatment of chronic hepatitis C genotype 1 infection in adults. Harvoni combines the NS5A inhibitor ledipasvir with the nucleotide analog polymerase inhibitor sofosbuvir, approved by the MHLW under the trade name Sovaldi® in March 2015. Harvoni is indicated for the suppression of viremia in patients with genotype 1 chronic hepatitis C virus (HCV) infection with or without compensated cirrhosis, with a treatment duration of 12 weeks.

"Today's approval significantly advances the standard of care for chronic hepatitis C in Japan, as it eliminates the need for interferon and ribavirin, which can be difficult to take and to tolerate, and offers the majority of people with genotype 1 infection to be cured in as little as 12 weeks with a once-daily pill," said Professor Masashi Mizokami, MD, PhD, The Research Center for Hepatitis and ImmunologyNational Center for Global Health and MedicineIchikawaJapan.

Primarily due to HCV, Japan has one of the highest rates of liver cancer of any industrialized country. Of the more than one million people in Japan chronically infected with HCV, 70-80 percent are infected with the genotype 1 strain of the virus.

Harvoni's approval in Japan is supported by data from 318 treatment-naïve and treatment-experienced Japanese patients with genotype 1 HCV infection randomized to ledipasvir/sofosbuvir (n=157) or ledipasvir/sofosbuvir plus ribavirin (n=161) in the Phase 3 clinical trial GS-US-337-0113. Of the 318 patients enrolled in this study, 34 percent were ages 65 years or older and 23 percent had cirrhosis.

Among patients receiving 12 weeks of ledipasvir/sofosbuvir without ribavirin, 100 percent (n=78/78) of treatment-naïve and 100 percent (n=79/79) of treatment-experienced patients achieved sustained virologic response 12 weeks after completing therapy (SVR12). Adverse events observed with ledipasvir/sofosbuvir without ribavirin were generally mild and included nasopharyngitis (29 percent), headache (7 percent) and malaise (6 percent).

The approval is also supported by results from three Phase 3 studies (ION-1, ION-2 and ION-3) evaluating eight, 12 or 24 weeks of ledipasvir/sofosbuvir among genotype 1 HCV patients. Trial participants included patients from the United StatesEurope and Puerto Rico who were treatment-naïve or who had failed previous treatment, including protease inhibitor-based regimens, and also included patients with compensated cirrhosis. Trial participants in the ribavirin-free arms (n=1,080) achieved SVR12 rates of 94 to 99 percent.

"Harvoni is a safe, simple and well-tolerated treatment. With cure rates of up to 100 percent and without the need for interferon or ribavirin, it offers genotype 1-infected patients a high likelihood of cure," said Norbert Bischofberger, PhD, Gilead's Executive Vice President, Research and Development, and Chief Scientific Officer. "We are pleased to have partnered with the medical community in Japan to demonstrate the safety and efficacy of two significant advances in the treatment of chronic hepatitis C – Harvoni for genotype 1 infection and Sovaldi for genotype 2 infection, which was approved just three months ago. We look forward to making Harvoni available in Japan as quickly as possible."

Important Safety Information About Harvoni in Japan

Warnings
Treatment with Harvoni should be initiated by a physician with sufficient knowledge and experience in the management of patients with viral liver diseases who are appropriately diagnosed to receive the treatment.

Contraindications
Harvoni is contraindicated in the following patients: Patients with a history of hypersensitivity to the active substances or to any of the excipients; patients with severe renal function impairment (eGFR<30mL/min/1.73m2) or patients with renal insufficiency requiring dialysis.

Contraindications for Coadministration

Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Carbamazepine, phenytoin, rifampin and St. John's wort should not be administered with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.

Important Precautions

Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with Harvoni due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.

Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi).

Adverse Reactions
The major adverse reactions were pruritus (3.2 percent), nausea (2.5 percent) and stomatitis (2.5 percent).

Drug Interactions
In addition to carbamazepine, phenytoin, rifampin and St. John's wort, coadministration of Harvoni is also not recommended with antacids, H2-receptor antagonists, proton-pump inhibitors, rifabutin and phenobarbital. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni.

Coadministration of Harvoni is not recommended with digoxin because the plasma concentration of digoxin may be increased. Coadministration is also not recommended with rosuvastatin or regimens containing tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.

Important Safety Information About Sovaldi in Japan

Warnings
Treatment with Sovaldi should be initiated by a physician with sufficient knowledge and experience in the management of patients with viral liver diseases who are appropriately diagnosed to receive the treatment.

Contraindications
Sovaldi is contraindicated in the following patients: Patients with a history of hypersensitivity to the active substances or to any of the excipients; patients with severe renal function impairment (eGFR<30mL/min/1.73m2) or patients with renal insufficiency requiring dialysis.

Contraindications for Coadministration

Risk of Reduced Therapeutic Effect of Sovaldi Due to P-gp Inducers: Carbamazepine, phenytoin, rifampin and St. John's wort should not be used with Sovaldi as they may significantly decrease sofosbuvir plasma concentration, reducing its therapeutic effect.

Important Precautions
Since Sovaldi is recommended for use in combination with ribavirin, the PRECAUTIONS of the ribavirin package insert, including Warnings, Contraindications, Careful Administration, Important Precautions, and Clinically Significant Adverse Reactions, must be consulted.

Adverse Reactions
The major adverse reactions observed in combination with ribavirin were anemia/hemoglobin decreased (15.0 percent), headache (5.0 percent), malaise (4.3 percent), nausea (4.3 percent) and pruritus (4.3 percent).

Drug Interactions
In addition to carbamazepine, phenytoin, rifampin and St. John's wort, coadministration of Sovaldi is not recommended with phenobarbital and rifabutin. Such coadministration is expected to decrease the concentration of sofosbuvir, reducing its therapeutic effect.

About Gilead
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. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

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