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Gilead Announces Scientific Presentations Demonstrating Efficacy of Harvoni® (Ledipasvir/Sofosbuvir) in Special Patient Populations With HCV Infection


Gilead Sciences, Inc. (NASDAQ:GILD) today announced results from two
Phase 2 studies evaluating Harvoni® (ledipasvir 90
mg/sofosbuvir 400 mg, LDV/SOF) tablets in chronic hepatitis C virus
(HCV)-infected patient populations not previously studied in dedicated
clinical trials with direct-acting antiviral therapies. The studies
demonstrated HCV cure rates of 99 percent in children aged 6 to 11 years
(#PS-101), and 100 percent in adult patients co-infected with HCV and
hepatitis B virus (HBV) (#PS-098). Detailed results from these studies
were presented this week at The International Liver CongressTM
2017 in Amsterdam.

Harvoni is approved in the United States for the treatment of genotype
1, 4, 5, or 6 chronic HCV infection in adults and pediatric patients 12
years of age or older or weighing at least 35 kilograms. Harvoni is
indicated with ribavirin (RBV) for the treatment of chronic HCV genotype
1 or 4 HCV infection in liver transplant recipients without cirrhosis or
with compensated cirrhosis and for genotype 1 HCV-infected patients with
decompensated cirrhosis.

Harvoni has a boxed warning in its product label regarding the risk of
hepatitis B virus reactivation in HCV/HBV co-infected patients. See
below for important safety information.

"Gilead continues to study the safety and efficacy of our medicines in
HCV-infected patients with unmet medical need, to help realize the
potential for cure," said Norbert Bischofberger, PhD, Executive Vice
President of Research and Development and Chief Scientific Officer,
Gilead Sciences. "In these studies of younger children with hepatitis C
and HCV/HBV co-infected patients, Harvoni achieved high cure rates and
demonstrated safety consistent with the known profile of the drug."

Children Aged 6 to 11 Years with Chronic HCV

The estimated prevalence of HCV infection in children is up to 0.4
percent in Europe and the United States and up to 6 percent in
resource-limited countries. For children 6-11 years of age weighing less
than 35 kilograms, interferon plus RBV for up to 48 weeks remains the
standard of care.

Results from an open-label Phase 2 study, led by Karen F. Murray, MD,
Professor of Pediatrics at Seattle Children's Hospital in Seattle,
Washington, evaluating an investigational dosage strength of a
once-daily single tablet of Harvoni (ledipasvir 45 mg/sofosbuvir 200 mg)
in HCV-infected children aged 6 to 11 years, demonstrated cure rates of
99 percent (n=89/90). Genotype 1 patients received 12 weeks of treatment
(n=85); one genotype 1 patient who had cirrhosis and prior treatment
failure with pegylated interferon plus RBV received 24 weeks of
treatment; genotype 3 patients (n=2) received Harvoni plus RBV for 24
weeks; genotype 4 patients (n=2) received Harvoni for 12 weeks. One
treatment-naïve genotype 1 patient relapsed; all other patients achieved
SVR12, the primary efficacy endpoint. The most common adverse events
(>10 percent) all of which were mild to moderate in severity, were
abdominal pain, headache, diarrhea, vomiting, nausea, fatigue, pyrexia,
cough and oropharyngeal pain. No patients discontinued therapy.

HCV/HBV Co-infected Patients

The global prevalence of HCV/HBV co-infection is estimated to be 1.7–3.9
million. Reactivation of HBV infection during treatment of HCV infection
with direct-acting antiviral agents has been reported in the
postmarketing setting. However, clinical trials to more systematically
assess the safety and efficacy of direct-acting antiviral therapy in
HCV/HBV co-infected patients with active HBV infection have not been

This Phase 2, open-label study led by Chun-Jen Liu, Professor of
Medicine at National Taiwan University in Taipei, Taiwan, evaluated 12
weeks of Harvoni in 111 genotype 1 or 2 HCV-infected patients in Taiwan
with active HBV co-infection (hepatitis B surface antigen positive), who
were not receiving HBV treatment. All patients achieved SVR12 (100
percent, 111/111) including 68 genotype 1 HCV-infected patients, 43
genotype 2 HCV-infected patients, 17 patients with compensated cirrhosis
and 37 with prior HCV treatment failure.

Three patients had serious adverse events that were not considered to be
drug-related, including optic neuritis, post-procedural bleeding and
duodenal ulcer bleeding. The most common adverse events reported (≥5
percent of patients) were headache, upper respiratory infection and

Of the 111 patients enrolled, 23 (21 percent) experienced an increase in
HBV DNA of at least 2 log10 IU/mL during or following Harvoni treatment.
However, no patient experienced a grade 3 or 4 ALT increase or any
clinical manifestations suggestive of HBV reactivation. There were two
patients that started HBV treatment based on increases in HBV DNA and
mild elevations in ALT without symptoms.

Further information about the clinical studies described above can be
found at

Certain uses for Harvoni highlighted above are investigational and have
not been determined to be safe or efficacious.

U.S. Important Safety Information for Harvoni


Test all patients for evidence of current or prior hepatitis B virus
(HBV) infection before initiating treatment with Harvoni.

HBV reactivation has been reported in HCV/HBV coinfected patients who
were undergoing or had completed treatment with HCV direct acting
antivirals (DAAs) and were not receiving HBV antiviral therapy. Some
cases have resulted in fulminant hepatitis, hepatic failure, and death.

Cases have been reported in patients who are HBsAg positive, in
patients with serologic evidence of resolved HBV, and also in patients
receiving certain immunosuppressant or chemotherapeutic agents; the risk
of HBV reactivation associated with treatment with HCV DAAs may be
increased in patients taking these other agents.

Monitor HCV/HBV coinfected patients for hepatitis flare or HBV
reactivation during HCV treatment and post-treatment follow-up. Initiate
appropriate patient management for HBV infection as clinically indicated.


  • If Harvoni is used in combination with ribavirin (RBV), all
    contraindications, warnings and precautions, in particular pregnancy
    avoidance, and adverse reactions to RBV also apply. Refer to RBV
    prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with
    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
  • Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin
    and St. John's wort are not recommended for use with Harvoni as they
    may significantly decrease ledipasvir and sofosbuvir plasma
  • Related Products Not Recommended: Harvoni is not recommended
    for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache
and asthenia.

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of
    Harvoni is also not recommended with carbamazepine, oxcarbazepine,
    phenobarbital, phenytoin, rifabutin, rifapentine, and
    tipranavir/ritonavir. 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 simeprevir due to
    increased concentrations of ledipasvir and simeprevir.
    Coadministration is also not recommended with rosuvastatin or
    co-formulated elvitegravir/cobicistat/emtricitabine/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.

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

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 physicians may not see the benefits of prescribing Harvoni in
special patient populations with HCV infection. 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, 2016, 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 Harvoni, including BOXED
, is available at

Harvoni is a registered trademark of Gilead Sciences, Inc., or its
related companies.

For more information on Gilead Sciences, please visit the company's
website at,
follow Gilead on Twitter (
or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

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