RESULTS OF PHASE III BRAVO TRIAL REINFORCE UNIQUE PROFILE OF LAQUINIMOD FOR MULTIPLE SCLEROSIS TREATMENT
· Primary endpoint of reducing annualized relapse rate was not statistically
· Following a standard adjustment, in accordance with a pre-defined sensitivity
analysis, laquinimod significantly reduced the annualized relapse rate (p=0.026)
· Laquinimod also demonstrated significant reductions in both brain volume loss
and the risk of disability progression, while maintaining a favorable safety and
· Regulatory submissions are planned in the U.S. and EU
· Teva to host conference call to discuss study results on August 1, 8:30 a.m.
Jerusalem, Israel and Lund, Sweden, August 1, 2011 - Teva Pharmaceutical
Industries Ltd. (NASDAQ: TEVA) and Active Biotech (NASDAQ OMX NORDIC: ACTI)
announced today initial results from the Phase III BRAVO study, which was
designed to evaluate the efficacy, safety and tolerability of oral laquinimod
compared to placebo and to provide a benefit-risk assessment comparing oral
laquinimod and a reference arm of injectable Interferon beta-1a (Avonex(®)).
BRAVO is the second of two pivotal Phase III studies in the clinical development
program for laquinimod, an investigational, oral, once-daily therapy for the
treatment of relapsing-remitting multiple sclerosis (RRMS). Results showed that
the BRAVO study did not achieve its primary endpoint of reducing the annualized
relapse rate (p=0.075).
The randomization process for BRAVO was adequately performed; however, placebo
and treatment study groups showed dissimilarity in two baseline magnetic
resonance imaging (MRI) characteristics. According to a standard and pre-
specified sensitivity analysis included within the original statistical analysis
plan, when this imbalance was corrected laquinimod demonstrated a significant
reduction in the annualized relapse rate (21.3%, p=0.026), in the risk of
disability progression as measured by Expanded Disability Status Scale (EDSS)
(33.5%, p=0.044) and in brain volume loss (27.5%, p<0.0001).
The BRAVO findings support the direct effect of laquinimod in the central
nervous system (CNS) and are in line with the results of the first laquinimod
Phase III trial, ALLEGRO. Additionally, as in ALLEGRO, the BRAVO study found
that laquinimod demonstrated a favorable safety and tolerability profile
compared to placebo.
Compared to placebo, treatment with Interferon beta-1a reduced annualized
relapse rates; however, a reduction in brain tissue loss was not demonstrated
and a reduction in the progression of disability was not significant.
The BRAVO study was not designed to provide direct statistical comparisons of
efficacy endpoints between the two active arms.
"We are encouraged by the overall outcomes achieved in the laquinimod Phase III
clinical development program, and plan to submit applications to regulatory
authorities in the U.S. and EU," said Professor Yitzhak Peterburg, Teva's Group
Vice President, Global Branded Products. "Teva remains committed to the
clinical development of laquinimod and is confident that the drug could provide
a unique option for the treatment of multiple sclerosis."
"Data from the ALLEGRO and BRAVO studies demonstrated that laquinimod reduced
disability and brain tissue loss, two of the most important goals in the
treatment of relapsing forms of multiple sclerosis," said Professor Per Soelberg
Sørensen, MD, Head of MS Research Unit, Copenhagen University Hospital,
Rigshospitalet, Co-principal investigator of the BRAVO study. "These effects,
coupled with a favorable safety profile and a once-daily dosing regimen create a
promising potential treatment for the disease."
Additional analyses of the BRAVO study data are ongoing, and results will be
submitted for presentation at a scientific congress later in the year.
Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA) will host an audio webcast on
August 1, 2011 at 8:30 a.m. EDT to discuss the results from the Phase III BRAVO
study of laquinimod. Those interested in listening to the webcast should log on
to http://www.tevapharm.com/financial/and register for the event (approximately
10 minutes before). The dial-in for this call is 1-800-299-6183 or 617-801-9713
internationally. The conference ID or passcode is 85409706. An archive of the
webcast will be available on Teva's website.
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.
Laquinimod is an oral, once-daily immunomodulator with a novel mechanism of
action being developed for the treatment of MS. The global Phase III clinical
development program evaluating oral laquinimod in MS consists of two pivotal
studies, ALLEGRO and BRAVO. In the ALLEGRO study, laquinimod demonstrated a
significant positive impact on disease activity, disability progression and MRI
measures of inflammation and neurodegeneration, while maintaining a favorable
safety and tolerability profile. Specifically, laquinimod showed a
statistically significant 23 percent reduction in annualized relapse rate and
36 percent significant reduction in the risk of confirmed disability
progression, as measured by EDSS.
In addition to the MS clinical studies, laquinimod is currently in Phase II
development for Crohn's disease and Lupus, and is being studied in other
ABOUT MULTIPLE SCLEROSIS
MS is the leading cause of neurological disability in young adults. It is
estimated that more than 400,000 people in the United States are affected by the
disease and that two million people may be affected worldwide. Multiple
sclerosis is a degenerative disease of the central nervous system in which
inflammation and axonal damage and loss result in the development of progressive
Teva Pharmaceutical Industries Ltd. (NASDAQ: 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 largest generic drug
maker, with a global product portfolio of more than 1,300 molecules and a direct
presence in about 60 countries. Teva's branded businesses focus on neurological,
respiratory and women's health therapeutic areas as well as biologics. Teva
currently employs approximately 42,000 people around the world and reached $16.1
billion in net sales in 2010.
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 www.activebiotech.comfor more information.
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remediation, our ability to identify, consummate and successfully integrate
acquisitions (including the acquisition of Cephalon), our ability to achieve
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approval of biotechnology-based products, our potential exposure to product
liability claims to the extent not covered by insurance, any failures to comply
with the complex Medicare and Medicaid reporting and payment obligations, our
exposure to currency fluctuations and restrictions as well as credit risks, the
effects of reforms in healthcare regulation and pharmaceutical pricing and
reimbursement, adverse effects of political or economical instability, major
hostilities or acts of terrorism on our significant worldwide operations,
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Active Biotech's Safe Harbor Statement in Accordance with the Swedish Securities
This press release contains certain forward-looking statements. Such forward-
looking statements involve known and unknown risks, uncertainties and other
important factors that could cause the actual results, performance or
achievements of the company, or industry results, to differ materially from any
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release any revisions to forward-looking statements to reflect events,
circumstances or changes in expectations after the date of this press release.
Active Biotech is required under the Financial Instruments Trading Act to make
the information in this press release public. The information was submitted for
publication at 2:00 p.m. CET on August 1, 2011.
RESULTS OF PHASE III BRAVO TRIAL REINFORCE UNIQUE PROFILE OF LAQ:
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