- Confirms results of phase II studies, with consistent
virologic response and tolerability profile
- Largest all-oral, interferon-free clinical program in
genotype 1 (GT1) patients to date(1)
- On track for major regulatory submissions in Q2
2014
- Worldwide, about 160 million people are chronically
infected with hepatitis C(2), most with GT1
NORTH CHICAGO, Illinois,
Nov. 18, 2013 /PRNewswire/ -- AbbVie
(NYSE: ABBV) released the first phase III results for the
investigational three direct-acting-antiviral (3D) regimen plus
ribavirin in patients chronically infected with genotype 1 (GT1)
hepatitis C virus (HCV). In the 631-patient SAPPHIRE-I study,
patients new to therapy receiving 12 weeks of AbbVie's 3D regimen
achieved a sustained virologic response at 12 weeks post-treatment
(SVR12) of 96 percent. The majority of patients were
GT1a, considered the more difficult-to-treat subtype, and the
SVR12 rates of GT1a and GT1b were 95 percent and 98
percent, respectively. The rate of virologic relapse or
breakthrough was low, occurring in 1.7 percent of patients
receiving the 3D regimen. In addition, discontinuation rates due to
adverse events were low, and of an equal percentage (0.6 percent)
in both active and placebo groups.
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-I is the first of
six phase III trials supporting AbbVie's investigational 3D regimen
for the treatment of GT1 hepatitis C patients.
"SAPPHIRE-I demonstrates that patients new to therapy with
genotype 1 HCV achieved high rates of virologic response with
AbbVie's interferon-free, all-oral 3D regimen plus ribavirin, and
the SVR rate is consistent with results from our phase II studies,"
said Scott Brun, M.D., vice
president, pharmaceutical development, AbbVie. "SAPPHIRE-I is the
first of these studies to report results, and based on the progress
of our clinical program to date, we are on track for major
regulatory submissions in the second quarter of 2014."
AbbVie will disclose detailed SAPPHIRE-I results at future
scientific congresses and in publications.
About Study M11-646 (SAPPHIRE-I)
SAPPHIRE-I 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-naive adult patients.
The study population consisted of 631 GT1 treatment-naive
patients with no evidence of liver cirrhosis with 473 patients
randomized to the 3D regimen plus ribavirin for 12 weeks, and 158
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.
Following 12 weeks of treatment with AbbVie's 3D regimen plus
ribavirin, 96 percent (n=455/473) of patients achieved
SVR12 based on intent-to-treat analysis where patients
with missing values for any reason were considered treatment
failures. In the active treatment arm, patients with GT1b infection
achieved 98 percent SVR12 (148/151), while patients with
GT1a achieved 95 percent SVR12 (307/322).
The most commonly reported adverse events in the 3D and placebo
arms, respectively, were fatigue, headache and nausea.
Discontinuations due to adverse events were reported in 0.6 percent
of patients receiving the 3D regimen and 0.6 percent of patients
receiving placebo. The rate of virologic relapse or breakthrough
was low, occurring in 1.7 percent of patients receiving the 3D
regimen.
Additional information about AbbVie's phase III studies can be
found on www.clinicaltrials.gov.
AbbVie's HCV Development Program
The clinical program supporting our 3D regimen includes more than
2,300 genotype 1 patients in greater 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 five 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 programs is as
follows:
|
|
Study
|
Patients
(N)
|
Treatment
Regimen
|
Treatment
Duration
|
|
SAPPHIRE-I
|
GT1,
treatment-naive
(631)
|
•
ABT-450/rb +ABT-267c
•
ABT-333
•
Ribavirin
|
12
weeks
|
|
• Placebo
|
12 weeks, then active treatment
for 12 weeks
|
|
SAPPHIRE-II
|
GT1,
treatment-experienced
(400a)
|
• ABT-450/r
+ABT-267
•
ABT-333
•
Ribavirin
|
12
weeks
|
|
• Placebo
|
12 weeks, then active treatment
for 12 weeks
|
|
PEARL-II
|
GT1b,
treatment-experienced
(210
a)
|
• ABT-450/r
+ABT-267
•
ABT-333
•
Ribavirin
|
12
weeks
|
|
• ABT-450/r
+ABT-267
• ABT-333
|
12
weeks
|
|
PEARL-III
|
GT1b,
treatment-naive
(400
a)
|
• ABT-450/r
+ABT-267
•
ABT-333
•
Ribavirin
|
12
weeks
|
|
• ABT-450/r
+ABT-267
•
ABT-333
•
Placebo
|
12
weeks
|
|
PEARL-IV
|
GT1a,
treatment-naive
(300
a)
|
• ABT-450/r
+ABT-267
• ABT-333
•
Ribavirin
|
12
weeks
|
|
• ABT-450/r
+ABT-267
•
ABT-333
•
Placebo
|
12
weeks
|
|
TURQUOISE-II
|
GT1,
treatment-naive and treatment-experienced (with compensated
cirrhosis)
(380
a)
|
• ABT-450/r
+ABT-267
•
ABT-333
•
Ribavirin
|
12
weeks
|
|
• ABT-450/r
+ABT-267
•
ABT-333
•
Ribavirin
|
24
weeks
|
|
|
|
|
|
| |
|
|
|
|
a projected
study population
|
|
b ABT-450/ritonavir
|
|
c ABT-267 is
co-formulated with ABT-450/r, administered as two pills once
daily
|
|
|
|
|
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 of HCV.
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 approved populations.
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 for
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.
About AbbVie
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.
Forward-Looking Statements
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 forward-looking statements. 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.
[1] Comparison based on review of data from clinicaltrials.gov
for phase 3a programs of Gilead, BMS and BI as of November 15, 2013
[2] Lavanchy D. Evolving epidemiology of hepatitis C virus.
Clin Microbiol Infect. 2011; 17(2):107-15.