Newly Published Phase III Exploratory Analysis Suggests Investigational Oral Laquinimod for Multiple Sclerosis May Reduce Brain Damage Caused by Neurodegeneration
* Pre-planned analysis of over 1,000 patients published online in the Journal
of Neurology, Neurosurgery & Psychiatry demonstrates the benefits of
laquinimod on neurodegeneration
* Laquinimod-treated patients accumulated significantly less brain tissue
damage caused by neurodegeneration, compared to placebo in MRI analyses
* Teva planning clinical trial in primary progressive multiple sclerosis
(PPMS) based on novel MOA demonstrated in Phase III trial program
Jerusalem & Lund, Sweden, October 1, 2013 - Teva Pharmaceutical Industries Ltd.
(NYSE: TEVA) and Active Biotech (NASDAQ OMX NORDIC: ACTI) announced today the
publication of a pre-planned analysis of the Phase III ALLEGRO study
demonstrating that once-daily oral laquinimod provides a beneficial impact on
brain tissue damage, one of the most destructive aspects of multiple sclerosis.
These data, "Placebo-controlled trial of oral laquinimod in multiple sclerosis:
MRI evidence of an effect on brain tissue damage," published online in September
by the Journal of Neurology, Neurosurgery & Psychiatry (JNNP), along with an
accompanying editorial titled, "Oral laquinimod for multiple sclerosis: beyond
the anti-inflammatory effect," can be found on the JNNP website at
www.jnnp.bmj.com.
"This Phase III sub-study was pre-planned to explore the ability of laquinimod
to act on mechanisms leading to irreversible brain tissue damage," said
Professor Massimo Filippi, Neuroimaging Research Unit, Institute of Experimental
Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-
Salute San Raffaele University. "This study indicates that laquinimod likely
exerts a favorable effect on several MRI metrics of neurodegeneration, which in
turn might explain the previously observed ability of the drug to significantly
slow down progression of locomotor disability in relapsing-remitting multiple
sclerosis."
The results showed that when compared with placebo, patients treated with
laquinimod experienced decreased rates in brain tissue damage shown by various
MRI markers. Specifically, patients receiving laquinimod showed decreased rates
of white matter (WM), grey matter (GM) and thalamic atrophy; developed fewer
permanent black holes (PBH); and accumulated less damage in normal appearing
brain tissue (NABT), WM and GM, when compared to patients receiving placebo.
"These analyses reinforce our faith in the potential of laquinimod and we are
proud to announce that we plan to initiate a clinical trial of the drug in PPMS
to gather even more evidence of this novel mechanism of action," said Dr.
Michael Hayden, President of Global R&D and Chief Scientific Officer for Teva
Pharmaceutical Industries Ltd. " We also believe the potential neuroprotective
benefits of laquinimod could have significant application in the treatment of
other diseases like Crohn's disease, lupus nephritis, Huntington's disease and
Alzheimer's."
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 is the time to confirmed disability
progression as measured by the EDSS. The study will also examine the impact of
laquinimod on endpoints such as percent change in brain volume, as well as other
clinical and MRI markers of disease activity.
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 32.8 percent reduction in progression of
brain atrophy (p<0.0001).
In these MRI analyses, white matter (WM), grey matter (GM) and thalamic
fractions were derived at baseline, and months 12 and 24. Also assessed were
evolution of gadolinium enhancing and/or new T2 lesions into permanent black
holes (PBH); magnetization transfer ratio (MTR) of normal-appearing brain tissue
(NABT), WM, GM and T2 lesions as assessed by magnetization transfer (MT) MRI;
and changes in n-acetylaspartate/creatinine (NAA/Cr) levels.
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.
The safety and tolerability profile of laquinimod observed in the ALLEGRO and
BRAVO studies was favorable. The overall frequencies of adverse events,
including incidence of infections, were similar 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.
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 is the 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. Because of the
neuroprotective findings, Teva is evaluating further studies to determine the
effectiveness of laquinimod in treating patients with primary progressive
multiple sclerosis, 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 pivotal phase
are laquinimod, an orally administered small molecule with unique
immunomodulatory properties for the treatment of multiple sclerosis, tasquinimod
for prostate cancer and ANYARA primarily for the treatment of renal cell cancer.
In addition, laquinimod is also in Phase II development for Crohn's and Lupus.
The company also has one additional project in clinical development, the orally
administered compound paquinimod (57-57) for systemic sclerosis. Please visit
http://www.activebiotech.com for more information.
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Market Act:
This press release contains certain forward-looking statements. Such forward-
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was provided to the media for publication 2:00 pm CET on October 1, 2013.
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Newly Published Phase III Exploratory Analysis Suggests Investigationa:
http://hugin.info/1002/R/1732669/579748.pdf
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