-- Once-Daily Single Tablet Regimen Eliminates the
Need for Interferon and Ribavirin for Patients with Genotype 1 and 4
Hepatitis C without Cirrhosis or with Compensated Cirrhosis --
FOSTER CITY, Calif.--(BUSINESS WIRE)--Nov. 18, 2014--
Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the European
Commission has granted marketing authorization for Harvoni®
(ledipasvir 90 mg/sofosbuvir 400 mg), the first once-daily single tablet
regimen to treat the majority of chronic hepatitis C genotype 1 and 4
infection in adults. Harvoni combines the NS5A inhibitor ledipasvir
(LDV) with the nucleotide analog polymerase inhibitor sofosbuvir (SOF),
approved by the European Commission under the tradename Sovaldi®
in January 2014.
Harvoni is indicated for the treatment of chronic hepatitis C virus
(HCV) in adults and is recommended in treatment-naïve and
treatment-experienced cirrhotic and non-cirrhotic genotype 1 and 4
patients with a treatment duration of 12 or 24 weeks depending on prior
treatment history and cirrhosis status. Eight weeks of treatment with
Harvoni may be considered in non-cirrhotic treatment-naïve genotype 1
patients. In genotype 1 and 4 patients with decompensated cirrhosis, and
genotype 3 patients with cirrhosis and/or prior treatment failure,
Harvoni should be used in combination with ribavirin for 24 weeks.
Harvoni is also indicated for patients with HCV who have HIV
Today’s marketing authorization is based on the clinical development
program that included more than 2,000 patients with HCV infection, and
follows an accelerated assessment by the European Medicines Agency, a
designation that is granted to new medicines of major public health
interest. It allows for the marketing of Harvoni in all 28 countries of
the European Union (EU).
“Genotype 1 patients living with hepatitis C in Europe and the
physicians who treat them have been waiting for a treatment advance like
this for decades,” said Graham Foster, MD, Professor of Hepatology,
Queen Mary University of London. “With Harvoni, we have the potential to
transform the way we treat people living with the most prevalent form of
hepatitis C in Europe. We can now expect very high SVR rates, and for
many patients, we can eliminate the need for interferon injections and
ribavirin and offer a cure in a once-daily tablet.”
The marketing authorization is supported primarily by data from three
Phase 3 studies, ION-1, ION-2 and ION-3. These studies evaluated eight,
12 or 24 weeks of treatment with Harvoni, with or without ribavirin,
among nearly 2,000 genotype 1 HCV patients with compensated liver
These studies included non-cirrhotic treatment-naïve patients (ION-3),
cirrhotic and non-cirrhotic treatment-naïve patients (ION-1) and
cirrhotic and non-cirrhotic patients who failed prior therapy with an
interferon-based regimen, including regimens containing an HCV protease
The primary endpoint for each study was sustained
virologic response (HCV undetectable) 12 weeks after completing therapy
(SVR12). Patients who achieve SVR12 are considered cured of HCV. In
these studies, ribavirin was not shown to increase response rates. Trial
participants in the ribavirin-free arms (n=1,080) achieved SVR12 rates
of 94 to 99 percent.
The approval was also supported by preliminary data from the SOLAR-1
trial, which evaluated difficult to treat patients with decompensated
cirrhosis and patients who have undergone liver transplantation, and
from the ERADICATE trial, which evaluated genotype 1 HCV patients
co-infected with HIV. The primary endpoint in these studies was SVR12.
At the time of submission, only preliminary results were available. In
the SOLAR-1 trial, participants with decompensated cirrhosis receiving a
12-week treatment regimen of Harvoni plus ribavirin had an SVR4 rate of
90 percent (n=45/50). In post-liver transplant patients without
decompensated liver disease, SVR4 rates were greater than 95 percent
(n=109). In an interim analysis of the ERADICATE trial, 40 of the 50
patients had reached 12 weeks post treatment and had SVR12 rates of 98
The ELECTRON-2 trial, a Phase 2 open-label study, provided preliminary
data on genotype 3 infected HCV patients demonstrating 100 percent
(n=26/26) SVR12 when Harvoni was used in combination with ribavirin for
In these clinical studies, fatigue and headache were more common in
patients treated with Harvoni compared to placebo.
Harvoni was approved by the U.S. Food and Drug Administration and Health
Canada in October 2014 and in New Zealand in November 2014. Regulatory
submissions for Harvoni are pending in Japan and Switzerland. Sovaldi as
a single agent is approved for use in the European Union and in the
United States, Canada, Australia, New Zealand, Egypt, Switzerland and
Important Safety Information
The summary of product characteristics of co-prescribed medicinal
products should be consulted before starting therapy with Harvoni.
About Gilead Sciences
- Harvoni should not be administered concomitantly with other medicinal
products containing sofosbuvir.
- In clinical studies, fatigue and headache were more common in patients
treated with Harvoni compared to placebo.
- Contraindications include hypersensitivity to the active substances or
to any of the excipients. Co-administration with rosuvastatin or St.
John’s wort (Hypericum perforatum) is contraindicated.
Co-administration with certain P-glycoprotein (P-gp) inducers (e.g.
rifampicin, carbamazepine and phenytoin) is not recommended. Monitoring
of digoxin and dabigatran is recommended when used with Harvoni. Caution
and frequent renal monitoring is recommended for co-administration with
certain HIV antiretroviral regimens.
- Safety has not been established in
patients with severe renal impairment. For patients on statins dose
reduction should be considered and careful monitoring for statin adverse
events (myopathy and rhabdomyolysis) should be undertaken. A Summary of
Product Characteristics is available at www.ema.europa.eu.
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
- See more at: http://gilead.com/news/press-releases/2014/11/european-commission-grants-marketing-authorization-for-gileads-harvoni-ledipasvirsofosbuvir-the-first-single-tablet-regimen-to-treat-the-majority-of-chronic-hepatitis-c-patients-with-genotype-1-and-4#sthash.YcamaUon.dpuf
Labels: EU commission approval, GT1, GT4, Harvoni