Pooled Data Analysis of Phase III ALLEGRO and BRAVO Studies Add to
our Understanding of Investigational Laquinimod for Relapsing-Remitting
Multiple Sclerosis (RRMS)
JERUSALEM & LUND, Sweden--(BUSINESS WIRE)--Oct. 4, 2013--
Teva Pharmaceutical Industries Ltd. (NYSE:TEVA) and Active Biotech
(NASDAQ OMX NORDIC:ACTI) announced today the presentation of additional
analyses of the Phase III ALLEGRO and BRAVO studies supporting the
hypothesis that once-daily, oral laquinimod may have an effect on both
inflammation and the broader underlying mechanisms associated with
disease progression in relapsing-remitting multiple sclerosis. Various
new laquinimod data will be featured in 16 scientific posters and
presentations at the 29th Congress of the European Committee for
Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen,
Denmark, October 2-5, 2013.
"Continued analysis of the ALLEGRO and BRAVO Phase III studies
demonstrates that the trend of efficacy results was maintained in the
analysis of data pooled from the two studies, and is consistent with the
proposed mechanism of action for laquinimod," said Dr. Michael Hayden,
President of Global R&D and Chief Scientific Officer for Teva
Pharmaceutical Industries Ltd. "Teva remains committed to the laquinimod
clinical development program in MS and in other diseases characterized
by a neurodegenerative pathology, and to addressing the needs of these
patients worldwide.”
Results from a post-hoc subgroup analysis of pooled data from the Phase
III double-blind ALLEGRO and BRAVO studies showed there were some
patients who experienced disease progression without experiencing a
relapse during the studies. Regardless of treatment arm and despite
relapse status, 12 percent of patients studied experienced disability
progression after two years; of those patients who progressed,
approximately one-third did not experience a relapse. Results specific
to treatment with laquinimod showed that both relapsing and relapse-free
patients treated with laquinimod experienced less disease progression
than those treated with placebo. Specifically, 19 percent of relapsing
patients on laquinimod progressed compared to 22 percent on placebo and
4.8 percent of relapse-free patients on laquinimod progressed compared
to 7.6 percent on placebo. Overall, laquinimod reduced disability
progression by 26.7 percent in relapsing patients (P=0.058) and 38.9
percent in relapse-free patients (P=0.036) compared to placebo.
Both the ALLEGRO and BRAVO studies found that laquinimod demonstrated a
tolerable clinical profile compared to placebo. The overall frequencies
of adverse events, including incidence of infections, were comparable to
those observed in the placebo group. The most commonly reported adverse
events were headaches, nasopharyngitis and back pain. The incidence of
liver enzyme elevation was higher in laquinimod treated patients;
however, these elevations were transient, asymptomatic and reversible.
No deaths were reported in laquinimod-treated patients.
“We have made significant progress in understanding the pathology of
multiple sclerosis however it remains a complex and often unpredictable
disease,” said Professor Giancarlo Comi, Director of the Department of
Neurology and Institute of Experimental Neurology at the San Raffaele
Scientific Institute, Vita-Salute San Raffaele University, Italy. “When
patients show disease progression but do not experience a relapse, it
suggests that disability progression and relapses are not solely
mediated through a common pathway. The data presented at ECTRIMS support
the theory that laquinimod may have a dual effect on inflammation and
broader underlying mechanisms of outside of inflammation.”
Results of this study will be presented at the ECTRIMS Congress on
Friday, October 4, 15:30 - 17:00 CET (P1036,
Poster Session: Long-term treatment monitoring).
ABOUT THE ALLEGRO STUDY
ALLEGRO was a two-year, multi-national, multi-center randomized, double
blind, placebo-controlled study designed to evaluate the efficacy,
safety and tolerability of laquinimod in MS patients. The study was
conducted at 139 sites in 24 countries and enrolled 1,106 MS patients.
Patients were randomized to receive a once-daily oral dose of 0.6 mg
laquinimod or matching placebo. The primary outcome measure was the
number of confirmed relapses; secondary measures included confirmed
disability progression and changes in MRI active lesions.
In the ALLEGRO study, laquinimod showed a statistically significant 23
percent reduction in annualized relapse rate (p=0.0024), the primary
endpoint, along with a significant 36 percent reduction in the risk of
confirmed disability progression, as measured by Expanded Disability
Status Scale (EDSS) (p=0.0122). Treatment with laquinimod was also
associated with a significant reduction in brain tissue loss, as
measured by a 33 percent reduction in progression of brain atrophy
(p<0.0001).
Eighty percent of laquinimod and 77 percent of placebo patients
completed the two-year study. Patients who completed the ALLEGRO study
were offered to join an open-label extension phase, in which they are
being treated with laquinimod 0.6 mg daily.
ABOUT THE BRAVO STUDY
BRAVO was a two-year, multi-national, multi-center, randomized,
double-blind, parallel-group, placebo-controlled study designed to
compare the safety, efficacy and tolerability of a once-daily oral dose
of 0.6 mg laquinimod over placebo and to provide a descriptive
comparison of the risk-benefit profiles of laquinimod and interferon
beta-1a. The primary outcome measure was to assess the efficacy of 0.6
mg daily dose of laquinimod as measured by the relapse rate. Secondary
outcome measures included impact on the accumulation of disability and
brain atrophy. The BRAVO study completed enrollment in June 2009,
recruiting more 1,331 patients at 153 sites worldwide, including in the
U.S., Europe, Russia, Israel and South Africa.
Results showed that the BRAVO study did not achieve its primary endpoint
of reducing the annualized relapse rate (p=0.075).
ABOUT LAQUINIMOD
Laquinimod is an oral, investigational, CNS-active immunomodulator with
a novel mechanism of action being developed for the treatment of
relapsing-remitting MS (RRMS). The global Phase III clinical development
program evaluating oral laquinimod in MS includes two pivotal studies,
ALLEGRO and BRAVO. A third Phase III laquinimod trial, CONCERTO, is
evaluating two doses of the investigational product (0.6mg and 1.2mg) in
approximately 1,800 patients for up to 24 months. The primary outcome
measure will be time to confirmed disability progression as measured by
the EDSS.
In addition to the MS clinical studies, laquinimod is currently in Phase
II of development for Crohn's disease and lupus nephritis. Further
studies are planned to determine the effectiveness of laquinimod in
treating patients with Huntington’s disease and Alzheimer’s disease.
ABOUT TEVA
Teva Pharmaceutical Industries Ltd. (NYSE:TEVA) is a leading global
pharmaceutical company, committed to increasing access to high-quality
healthcare by developing, producing and marketing affordable generic
drugs as well as innovative and specialty pharmaceuticals and active
pharmaceutical ingredients. Headquartered in Israel, Teva is the world's
leading generic drug maker, with a global product portfolio of more than
1,000 molecules and a direct presence in about 60 countries. Teva's
branded businesses focus on CNS, oncology, pain, respiratory and women's
health therapeutic areas as well as biologics. Teva currently employs
approximately 46,000 people around the world and reached $20.3 billion
in net revenues in 2012.
ABOUT ACTIVE BIOTECH
Active Biotech AB (NASDAQ OMX NORDIC:ACTI) is a biotechnology company
with focus on autoimmune/inflammatory diseases and cancer. Projects in
or entering pivotal phase are laquinimod, an orally administered small
molecule with unique immunomodulatory properties for the treatment of
multiple sclerosis, TASQ for prostate cancer as well as ANYARA for use
in cancer targeted therapy, primarily of renal cell cancer. In addition,
laquinimod is in Phase II development for Crohn's and Lupus. Further
projects in clinical development comprise the two orally administered
compounds, 57-57 for SLE & Systemic Sclerosis and RhuDex(TM) for RA.
Please visit http://www.activebiotech.com
for more information.
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Source: Teva Pharmaceutical Industries Ltd.