New Preclinical Data Suggests FTY720 May Repair or Reduce Damage Caused by Multiple Sclerosis Through a Direct Effect in the Brain
* Potential beneficial impact on central nervous system in addition to well established action on immune cells
* Recruitment complete for two of three pivotal Phase III trials;
recruitment for third study is ongoing and on track
* MS most common neurological disorder in young adults, affecting
more than an estimated 2.5 million people worldwide
EAST HANOVER, N.J., Oct. 12, 2007- New preclinical data presented
at European Committee for Treatment and Research of Multiple
Sclerosis (ECTRIMS) in Prague suggests that FTY720 (fingolimod)
directly reduces neurodegeneration and enhances repair of the
central nervous system (CNS) damage caused by multiple sclerosis
(MS) by interacting with sphingosine-1-phosphate receptors (S1P-R)
expressed on brain cells. This mechanism of action may be in
addition to the established anti-inflammatory role of FTY720 that
is mediated by the reduction of inflammatory immune cells, called
lymphocytes, from reaching the brain.
FTY720 is a novel, once-daily, oral treatment currently in
worldwide Phase III clinical development to test its safety and
efficacy as a disease modifying therapy for relapsing-remitting MS,
which affects approximately 85% of people with multiple
sclerosis.
The potential direct beneficial effect of FTY720 in the CNS is
supported by the results of several preclinical experiments being
presented at ECTRIMS, including research in animal models of MS and
in vitro studies on CNS cells called oligodendrocytes.
In an animal model of MS (experimental autoimmune encephalomyelitis
in rats), the administration of FTY720 directly into the CNS
resulted in a statistically significant reduction in disease
severity. This decrease in disease activity was seen in the absence
of a reduction of lymphocytes in the bloodstream, suggesting that
the favorable effect of FTY720 seen in this model is due to a
direct effect in the CNS that is independent of the effects on
peripheral lymphocytes.
In two experiments presented at ECTRIMS, the modulation of S1P-R by the addition of FTY720 resulted in an increase in the number, growth and survival of oligodendrocytes in cell culture. This effect of FTY720 on oligodendrocytes may help limit destruction of myelin and promote its repair and, thus, may contribute to the effectiveness of FTY720 in MS. Oligodendrocytes are cells in the CNS that make a fatty tissue, called myelin, which is necessary for normal signal transfer along nerve fibers in the CNS. Myelin and oligodendrocytes are typically damaged in MS.
"FTY720 crosses the blood-brain barrier and the drug's target - S1P
receptors - are present on brain cells, including oligodendrocytes
as shown in animal cell studies," said Jack Antel, Professor,
Department of Neurology and Neurosurgery, McGill University,
Montreal, Canada. "We are able to confirm that FTY720 directly
modulates the S1P receptors on human oligodendrocyte progenitor
cells."
FTY720 is currently being investigated in the largest worldwide
Phase III clinical trial program to be conducted in MS to evaluate
further its efficacy and safety as a disease modifying therapy for
relapsing-remitting MS. This comprehensive program includes trials
referred to as FREEDOMS, FREEDOMS II and TRANSFORMS. Recruitment is
complete for FREEDOMS and TRANSFORMS. Recruitment is ongoing and on
track for FREEDOMS II and FTY720 regulatory filing is planned for
the second half of 2009. For more information about the clinical
trial program, including eligibility criteria and location of U.S.
study sites, patients can call the following toll-free number:
866-788-3930, or visit www.MSClinicalTrials.com.
"Novartis has a significant long-term investment and commitment to
multiple sclerosis and neuroscience through its extensive research
and development program," said Ludwig Hantson, PhD, Senior VP for
Commercial Development & Specialty Businesses at Novartis
Pharmaceuticals Corporation. "We believe oral FTY720 is an exciting
and promising experimental therapy for MS as shown by the
compelling Phase II data. As an oral therapy with a novel mechanism
of action and promising efficacy, FTY720 has the potential to be a
significant and innovative therapeutic advance."
Phase II Study Results
The six-month, placebo-controlled Phase II study conducted in 281 patients with relapsing MS in 11 countries (Europe and Canada) showed that oral FTY720, taken once-daily, reduced relapse rates by more than 50% compared to placebo and reduced MRI (magnetic resonance imaging) measures of inflammation with approximately 80% of patients free of active brain lesions.
In patients continuously treated with FTY720 for up to two years
(placebo-controlled study plus the extension trial), up to 77% of
patients were relapse-free and more than 80% of patients were free
of active brain lesions at two years.
In the six-month placebo-controlled phase of the Phase II study,
the most frequent adverse events reported for FTY720 were
dose-dependent upper respiratory tract infections (mainly
nasopharyngitis) and dyspnea, plus diarrhea and nausea. FTY720
treatment was associated with initial dose-dependent decreases in
heart rate and expiratory air flow. Clinically asymptomatic
increases in alanine aminotransferase (liver enzyme) and an
increase in blood pressure were also observed. No unexpected
adverse events emerged in patients treated for up to 24 months
compared with the six-month placebo-controlled phase. There was no
further elevation of blood pressure with continued treatment beyond
the effect seen at six months.
The ongoing Phase III study program includes comprehensive
monitoring, which will provide further characterization of the
safety profile of FTY720.
Multiple Sclerosis
MS is the most common disorder of the CNS in young adults, affecting more than an estimated 2.5 million people worldwide. It is a progressive and debilitating disorder caused by the destruction of myelin, which helps neurons carry electrical signals in the brain. MS causes problems with muscle control and strength, vision, balance, sensation and mental function. MS typically presents in relapsing forms involving acute self-limiting attacks of neurological dysfunction (or "relapses") followed by complete or partial restoration of functions.
Disclaimer
This release contains certain forward-looking statements relating to Novartis' business, which can be identified by the use of forward-looking terminology such as "may," "suggests," "suggesting," "potential," "promising," "planned" or similar expressions, or by express or implied statements regarding the potential approval of FTY720 by health authorities for marketing, whether or not FTY720 will be the first orally effective MS treatment, the potential health effects or long-term impact of a patient's use of FTY720, or potential future revenue from FTY720. Such forward-looking statements reflect the current views of Novartis regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with FTY720 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that FTY720 will be approved for any indications or labeling in any market. Neither can there be any guarantee that, if approved, it will be the first orally effective MS treatment. Neither can there be any guarantee regarding the health effects or long-term impact of a patient's use of FTY720. Neither can there be any guarantees that FTY720 will reach any particular levels of revenue. In particular, management's expectations regarding FTY720 could be affected by, among other things, unexpected clinical trial results, including new clinical trial results and additional analysis of existing results; unexpected regulatory actions or delays or government regulation generally; competition in general; Novartis' ability to obtain or maintain patent or other proprietary intellectual property protection; government, industry and general public pricing pressures, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
About Novartis
Novartis has been a leader in the neuroscience area for more than 50 years, having pioneered early breakthrough treatments for Alzheimer's disease, Parkinson's disease, Attention Deficit Hyperactivity Disorder, epilepsy, schizophrenia and migraine, many of which continue to be regarded as "gold standards" to this day. Novartis continues to be at the forefront of research and development of new compounds and is committed to addressing unmet medical needs and to supporting patients and families affected by these disorders.
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Novartis Media Relations
Christine Cascio
Communications
Novartis Pharmaceuticals Corporation
+1 862 778 8026 (direct)
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christine.cascio@novartis.com
christine.cascio@novartis.com>
Tom Jones
Communications
Novartis Pharmaceuticals Corporation
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tomc.jones@novartis.com
e-mail: media.relations@novartis.com
Posted: October 2007
