AbbVie Demonstrates 96 percent SVR(12) in its Phase III Study of
Treatment-Experienced Patients with Genotype 1 Hepatitis C
NORTH CHICAGO, Illinois, Dec. 10, 2013
-Results further confirm phase II studies, with consistent virologic response
and tolerability profile-
-SAPPHIRE-II is the second of six phase III trials studying the
investigational 3D regimen-
-Future data anticipated from AbbVie's clinical trials examines 3D regimen
with and without ribavirin, as well as treatment of hepatitis C in patients
NORTH CHICAGO, Illinois, Dec. 10, 2013 /PRNewswire/ -- AbbVie (NYSE: ABBV)
released phase III results for the investigational three
direct-acting-antiviral (3D) regimen plus ribavirin in patients with chronic,
genotype 1 (GT1) hepatitis C virus (HCV) infection. In the 394-patient
SAPPHIRE-II study, 96 percent of patients who previously failed pegylated
interferon and ribavirin treatment, including approximately 49 percent of who
were prior null responders, achieved sustained virologic response at 12 weeks
(SVR12) with the regimen. The majority of patients were GT1a, considered a
difficult-to-treat subtype, and the SVR12 rates of GT1a and GT1b were 96
percent and 97 percent, respectively. Virologic relapse or breakthrough was
noted in 2 percent of patients receiving the 3D regimen plus ribavirin. In
addition, the discontinuation rate due to adverse events was 1 percent.
Globally, approximately 160 million people are chronically infected with
hepatitis C. AbbVie's multinational HCV program is the largest all-oral,
interferon-free clinical program in GT1 patients being conducted to date.
GT1 (with subtypes 1a and 1b) is the most prevalent genotype worldwide, with a
higher prevalence of 1a in the U.S. and 1b in Europe.
"SAPPHIRE-II demonstrates that treatment-experienced genotype 1 HCV patients
achieved high rates of virologic response with AbbVie's interferon-free,
all-oral 3D regimen plus ribavirin," said Scott Brun, M.D., vice president,
pharmaceutical development, AbbVie. "Completion of the two placebo-controlled
SAPPHIRE studies is an important step in AbbVie's HCV clinical development
program. We look forward to the results of studies looking at AbbVie's 3D
regimen with and without ribavirin in different patients, as well as data from
our dedicated study in patients with cirrhosis."
About Study M13-098 (SAPPHIRE-II)
Following SAPPHIRE-I, SAPPHIRE-II is the second placebo-controlled trial and
the second of six phase III trials supporting AbbVie's investigational 3D
regimen for the treatment of GT1 hepatitis C patients. AbbVie will disclose
detailed SAPPHIRE-II results at future scientific congresses and in
SAPPHIRE-II is a global, multi-center, randomized, double-blind,
placebo-controlled study to evaluate the efficacy and safety of 12 weeks of
treatment with ABT-333 (250mg), ribavirin (weight-based), both dosed twice
daily, and the fixed-dose combination of ABT-450/ritonavir (150/100mg)
co-formulated with ABT-267 (25mg) and dosed once daily in non-cirrhotic, GT1a
and GT1b HCV-infected, treatment-experienced adult patients who previously
failed treatment with pegylated interferon and ribavirin.
The study population consisted of 394 GT1 treatment-experienced patients with
no evidence of liver cirrhosis with 297 patients randomized to the 3D regimen
plus ribavirin for 12 weeks, and 97 patients randomized to placebo for the
initial 12 weeks. Patients initially randomized to placebo for the first 12
weeks then received open-label treatment with the 3D regimen plus ribavirin
for 12 weeks. In the study, 49 percent of patients were prior null responders
to pegylated interferon and ribavirin, generally considered among the most
difficult to treat successfully.
Following 12 weeks of treatment with AbbVie's 3D regimen plus ribavirin, 96
percent (n=286/297) of patients achieved SVR12 based on intent-to-treat
analysis where patients with missing values for any reason were considered
treatment failures. The SVR12 rates in GT1a and GT1b patients were 96 percent
(166/173) and 97 percent (119/123), respectively. One subject had HCV genotype
1 and achieved SVR12, but was unable to be subgenotyped.
The most commonly reported adverse events in both the 3D and placebo arms were
headache, fatigue and nausea. Discontinuations due to adverse events were
reported in three (1 percent) patients receiving the 3D regimen and no
patients receiving placebo. Virologic relapse or breakthrough was noted in 2
percent of patients receiving the 3D regimen plus ribavirin.
Additional information about AbbVie's phase III studies can be found on
AbbVie's HCV Development Program
The clinical program supporting our 3D regimen includes more than 2,300 GT1
patients in more than 25 countries around the world. The AbbVie HCV clinical
development program is intended to advance scientific knowledge and clinical
care by investigating an interferon-free, all-oral 3D regimen with or without
ribavirin with the goal of producing high SVR rates in as many patients as
possible, including those that typically do not respond well to treatment,
such as previous non-responders to interferon-based therapy or patients with
advanced liver fibrosis or cirrhosis. Results from the remaining four studies
in AbbVie's phase III program will be available in the coming months,
supporting regulatory submissions starting in the second quarter of 2014.
Overview of AbbVie's phase III clinical program is as follows:
Study Patients (N) Treatment Regimen Duration
SAPPHIRE-I GT1, treatment-naive *ABT-450/r b 12 weeks
12 weeks, then
*Placebo 12 weeks
SAPPHIRE-II GT1, treatment-experienced *ABT-450/r 12 weeks
12 weeks, then
*Placebo 12 weeks
PEARL-II GT1b, treatment-experienced *ABT-450/r 12 weeks
(210 ^ a) *ABT-333
*ABT-450/r 12 weeks
PEARL-III GT1b, treatment-naive *ABT-450/r 12 weeks
(400 ^ a) *ABT-333
*ABT-450/r 12 weeks
PEARL-IV GT1a, treatment-naive *ABT-450/r 12 weeks
(300 ^ a) *ABT-333
*ABT-450/r 12 weeks
TURQUOISE-II GT1, treatment-naive and *ABT-450/r 12 weeks
treatment-experienced (with +ABT-267
compensated cirrhosis) *ABT-333
(380 ^ a) *ABT-450/r 24 weeks
a projected study population
c ABT-267 is co-formulated with ABT-450/r, administered as two pills once
The 3D regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A
inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333. The
combination of three different mechanisms of action interrupts the HCV
replication process with the goal of optimizing SVR rates across different
patient populations. In May of 2013, AbbVie's investigational 3D regimen with
and without ribavirin for HCV GT1 was designated as a Breakthrough Therapy by
the U.S. Food and Drug Administration (FDA).
ABT-450 was discovered during the ongoing collaboration between AbbVie and
Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens
that include protease inhibitors. ABT-450 is being developed by AbbVie for use
in combination with AbbVie's other investigational medicines for the treatment
Safety Information for Ribavirin and Ritonavir
Ribavirin and ritonavir are not approved for the investigational use discussed
above, and no conclusions can or should be drawn regarding the safety or
efficacy of these products for this use.
There are special safety considerations when prescribing these drugs in
Ritonavir must not be used with certain medications due to significant
drug-drug interactions and in patients with known hypersensitivity to
ritonavir or any of its excipients.
Ribavirin monotherapy is not effective for the treatment of chronic hepatitis
C virus and must not be used alone for this use. Ribavirin causes significant
teratogenic effects and must not be used in women who are pregnant or
breast-feeding and in men whose female partners are pregnant. Ribavirin must
not be used in patients with a history of severe pre-existing cardiac disease,
severe hepatic dysfunction or decompensated cirrhosis of the liver,
automimmune hepatitis, hemoglobinopathies, or in combination with
peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and
Child-Pugh score ≥6.
See approved product labels for more information.
AbbVie is a global, research-based biopharmaceutical company formed in 2013
following separation from Abbott. The company's mission is to use its
expertise, dedicated people and unique approach to innovation to develop and
market advanced therapies that address some of the world's most complex and
serious diseases. In 2013, AbbVie employs approximately 21,000 people
worldwide and markets medicines in more than 170 countries. For further
information on the company and its people, portfolio and commitments, please
visit www.abbvie.com . Follow @abbvie on Twitter or view careers on our
Facebook or LinkedIn page.
Some statements in this news release may be forward-looking statements for
purposes of the Private Securities Litigation Reform Act of 1995. The words
"believe," "expect," "anticipate," "project" and similar expressions, among
others, generally identify forward-looking statements. AbbVie cautions that
these forward-looking statements are subject to risks and uncertainties that
may cause actual results to differ materially from those indicated in the
Such risks and uncertainties include, but are not limited to, challenges to
intellectual property, competition from other products, difficulties inherent
in the research and development process, adverse litigation or government
action, and changes to laws and regulations applicable to our industry.
Additional information about the economic, competitive, governmental,
technological and other factors that may affect AbbVie's operations is set
forth in Item 1A, "Risk Factors," in AbbVie's 2012 Annual Report on Form
10-K/A, which has been filed with the Securities and Exchange Commission.
AbbVie undertakes no obligation to release publicly any revisions to
forward-looking statements as a result of subsequent events or developments,
except as required by law.
 Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol
Infect. 2011; 17(2):107-15.
 Comparison based on review of data from clinicaltrials.gov for phase 3a
programs of Gilead, BMS and BI as of November 15, 2013
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