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Two year Phase III study shows Novartis oral MS therapy FTY720 (fingolimod) significantly reduces relapses and disability progression in relapsing-remitting multiple sclerosis

For UK consumer health journalists

• Fingolimod significantly reduced annualised relapse rates by 54-60% vs placebo and disability progression by 30-32% in two-year FREEDOMS study1

• Results build on Phase III TRANSFORMS one-year study showing fingolimod reduced relapses significantly more than interferon beta-1a, a standard of care1,2

• Phase III efficacy and safety data confirm positive benefit-risk profile for lower 0.5 mg dose of fingolimod 1and support planned EU submissions at the end of 2009

Resources to support this story (UK spokespeople interviews, mode of action photos and video, fingolimod fact sheet and patient video) are available. For media enquiries, contact Aurora Healthcare Communications on 020 7424 7940.

Frimley, 30th September, 2009 – Novartis Pharmaceuticals UK Ltd. announced today that initial results from the Phase III FREEDOMS study confirmed the two-year efficacy of FTY720 (fingolimod), a once-daily oral treatment currently in development for people with relapsing-remitting multiple sclerosis (RRMS).1 Patients taking fingolimod experienced significantly fewer relapses than patients taking placebo and had significantly reduced disability progression compared to those on placebo over two years.1

The FREEDOMS study met its primary and secondary endpoints – reduction in annualised relapse rate and reduced disability progression [as measured by the time to three month confirmed disability progression as measured by EDSS] compared to placebo – for both doses of fingolimod tested (0.5 mg and 1.25 mg), with no significant difference in efficacy between doses.1 This result builds on previous data showing superior efficacy to interferon beta-1a in TRANSFORMS, a large Phase III head-to head study.2

In FREEDOMS, fingolimod had a lower incidence of adverse events at the 0.5 mg dose than the 1.25 mg dose.1 Regulatory submissions for fingolimod in the EU, planned for the end of 2009, will seek approval for the lower 0.5 mg dose of fingolimod, based on comprehensive Phase III data establishing its positive benefit-risk profile and future development in RRMS will focus on the 0.5 mg dose.

"FREEDOMS reinforces the potential for fingolimod as a significant breakthrough in the future treatment of relapsing-remitting MS by reducing annualised relapse rates and reducing the progression of disability, which is one of the biggest concerns for patients and a key goal of treatment." said Professor David Bates, FREEDOMS investigator and Professor of Clinical Neurology at the University of Newcastle upon Tyne.

He continued, "These results mean that a patient who would have had an attack every three years might expect one only every six to seven years. This, in itself, reduces the degree of disability."

Patients taking fingolimod 0.5 mg had the annualised relapse rate reduced by 54% compared to placebo at two years (p<0.001).1 Patients taking fingolimod 1.25 mg had the annualised relapse rate reduced by 60% at two years compared to placebo (p=<0.001).1

Fingolimod also reduced the risk of confirmed disability progression (a key secondary endpoint) compared to placebo over two years by 30% for patients taking fingolimod 0.5 mg [p=0.024] and 32% for patients taking fingolimod 1.25 mg [p=0.017].1 These findings were supported by positive effects on brain lesions as measured by magnetic resonance imaging (MRI) scans. Disability progression was defined as an increase from baseline on Expanded Disability Status Scale (EDSS) scores confirmed at three months.1

“These data are exciting because fingolimod is an oral therapy and a new class of drug, it has good efficacy and could offer patients with relapsing-remitting MS another treatment choice.” said Dr Eli Silber, FREEDOMS investigator and Consultant Neurologist who leads an MS service for South London based at King’s College Hospital.

Miss Donna Clements, Neurology Research Nurse at Norfolk and Norwich University Hospitals NHS Foundation Trust adds, “The option of a once-daily oral treatment as a capsule will potentially revolutionise the lives of people with relapsing-remitting MS.” She continued, “Many people dislike or experience problems with injectable treatments and it can be difficult to travel abroad with fluids and needles.”

FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis) was a 24-month, double-blind, placebo-controlled study designed to assess the efficacy, safety and tolerability of two doses of fingolimod (0.5 mg and 1.25 mg), as well as the effect of fingolimod on disability progression over two years. The study was conducted in 22 countries worldwide, excluding the United States and involved 1,272 patients with RRMS. 37 patients took part in the study at six centres across the UK.1,3

Fingolimod has a well-studied safety profile with more than 5,300 patient years of exposure across the MS clinical trial programme, including more than 140 patients monitored for more than five years and certain patients in their sixth year of treatment.1 Previous data from the development programme raised questions about potential side effects including macular oedema, melanoma, liver injury, infections, and increased blood pressure. In the FREEDOMS study, at the 0.5 mg dose there were no cases of macular oedema or melanoma.1 Reversible and generally asymptomatic liver enzyme elevations were observed more frequently with fingolimod than placebo, and lung infections were also slightly more common. Mild elevation in blood pressure was observed with fingolimod. No new safety signals were seen in FREEDOMS compared to previous clinical trials. Three patients died during the FREEDOMS study, one on FTY720 1.25 mg and two on placebo. None of the deaths was assessed as being related to the study drug.1

FREEDOMS is the second of three registration studies to report results in a Phase III clinical trial programme being conducted by Novartis evaluating fingolimod in MS. Recently reported results of the first pivotal study, TRANSFORMS, demonstrated that fingolimod had superior efficacy to interferon beta-1a (Avonex®) an established standard of care in RRMS in terms of reduced annual relapse rate, and certain markers of disease activity, as seen on MRI.2

The third study, INFORMS, is investigating the efficacy of fingolimod versus placebo in primary progressive multiple sclerosis (PPMS) over three years. There is currently no licensed treatment for people with PPMS.

Comprehensive analyses of the FREEDOMS study data are ongoing, and detailed results are planned to be presented at a leading scientific congress in 2010. Regulatory submissions for fingolimod remain on track to be completed in the EU at the end of this year.

About fingolimod
Fingolimod, is a new, once-daily oral treatment for people with RRMS and PPMS, currently in worldwide Phase III clinical development.4
There are no oral treatments currently licensed for MS in the UK. Current treatments are administered either by subcutaneous or intramuscular injection or intravenous infusion.5,6
Fingolimod has a novel mode of action; it is a sphingosine 1-phosphate (S1P) receptor modulator.7
Fingolimod targets MS via S1P receptors found on lymphocytes (which are blood cells forming part of the immune system)1,2,8
- As such, fingolimod temporarily ‘parks’ lymphocytes in the lymph nodes, thereby reducing the number of lymphocytes circulating in the blood stream
- The number of lymphocytes reaching the brain is consequently reduced, resulting in decreased inflammatory damage within the central nervous system
- The immune system effects are reversible, allowing circulating lymphocytes to regain normal levels within weeks if treatment is stopped.

Novartis in MS
Novartis has been highly active in neuroscience for more than 50 years, having developed treatments for conditions including epilepsy, ADHD, Alzheimer's disease and schizophrenia. Novartis continues to be active in the research and development of new compounds, is committed to addressing unmet medical needs and to supporting patients and their families affected by MS.

The foregoing release contains forward-looking statements that can be identified by terminology such as “planned,” “future,” “to focus on,” “will,” “potential,” “potentially,” or similar expressions, or by express or implied discussions regarding potential future regulatory submissions or approvals for FTY720 or regarding potential future revenues from FTY720. You should not place undue reliance on these statements. Such forward looking statements reflect the current views of management 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 submitted or approved for sale in any market. Nor can there be any guarantee that FTY720 will achieve any particular levels of revenue in the future. In particular, management’s expectations regarding FTY720 could be affected by, among
other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; competition in general; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities
as recorded in the Group's consolidated balance sheet, 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 materialise, 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 provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2008, the Group’s continuing operations achieved net sales of USD 41.5 billion and net income of USD 8.2 billion. Approximately USD 7.2 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 99,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit

Please note that FTY720 (fingolimod) is an investigational drug and has not been approved or licensed anywhere in the world (September 2009).

Media contacts

Claire Eldridge / Siân Hurst / Aaron Pond
Aurora Healthcare Communications
Tel: 0207 424 7940
Mobile: 07736 277 106 / 07949 733 493 / 07872 812 405

Novartis Communications UK
Tel: 01276 698 691 (Press Office)

Notes to Editors:

About Multiple Sclerosis
While its exact cause is unknown, MS is a chronic autoimmune neurodegenerative disease of the central nervous system (CNS) – the brain and spinal cord – associated with irreversible progression of disability.9 It is the most common disease of the CNS in young adults, affecting around 100,000 people in the UK.10 About 2,500 people in the UK are diagnosed with MS each year – 50 people each week.10 It typically begins in early adulthood between the ages of 20 and 40 years.10,11 Research suggests one person in 50 with MS is diagnosed in their teens or younger.10 Women are almost twice as likely to develop MS as men.10,11

MS is a complex and unpredictable condition that varies from person to person and does not follow a set pattern.12 Symptoms can come and go from day to day but there can also be relapses followed by periods of complete or partial remission.12 For other people, MS can be more progressive in nature.12

Common symptoms at the time of diagnosis may include fatigue, loss of vision in one eye, blurred or double vision, dragging a foot, weakness of limbs, reduced coordination, balance problems, numbness, pins and needles, and burning sensations.13

MS is often divided into four different types:12
Benign MS - Associated with very occasional relapses, with good recovery in between and minimal symptoms over many years; therefore it can only be diagnosed retrospectively. Some neurologists estimate that more than 20% of people with MS have this benign form of the condition.
Relapsing-remitting MS initially affects two thirds of people with MS. They experience relapses on average once or twice per year, with good or complete remission in between. However, there is a tendency for symptoms to worsen very gradually over time. A relapse is a significant worsening or a re-occurrence of a symptom, or a group of symptoms, lasting for more than 24 hours. Symptoms usually appear over a short period of time (hours or days), but can last for anywhere between a few days to many months. The severity of a relapse can also vary from mild to more severe. A remission is a period of recovery, when symptoms become less severe or disappear altogether. Periods of remission can last any length of time, sometimes even for years.
Secondary progressive - People who start off with relapsing/remitting MS may go on to develop a progressive form of the condition; on average this occurs 15-20 years after diagnosis. The severity and frequency of the relapses decrease, but disability slowly increases.
Primary progressive - About 10% of people experience symptoms right from the start that become progressively worse over a period of years without remission.

Current methods of treating MS
Treatment of relapses – Corticosteroids are commonly used to speed up recovery from relapses although there is no evidence that they impact on long term outcomes.5
Symptomatic treatment – Several drugs are available to alleviate specific symptoms, such as bladder problems, spasms, spasticity and pain.5
Disease modifying therapies (DMTs) – Long-term treatment to reduce the number, duration and severity of relapses. May also delay disease progression. Each DMT requires frequent injections5 (ranging from every day to weekly) and they may result in injection site reactions and flu-like symptoms.5,14 One drug, indicated for rapidly evolving MS is given as a once monthly infusion.6 To date, there are no approved oral DMTs for MS.

About the Expanded Disability Status Scale (EDSS)15
The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. It is widely used in clinical trials and in the assessment of people with MS. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist.

1. Novartis. Data on file
2. Cohen J et al. Oral Fingolimod (FTY720) versus interferon beta-1a in relapsing–remitting multiple sclerosis: results from a phase III study (TRANSFORMS). Oral presentation at the American Academy of Neurology annual meeting 2009
3. Last accessed 23 September 2009
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7. Foster CA et al. Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosis. J Pharmacol Exp Ther 2007, 323 (2) 469-76.
8. Last accessed 15 September 2009
9. Confavreux C, Vukusic S,. Accumulation of irreversible disability in multiple sclerosis: from epidemiology to treatment. Clin Neurol Neurosurg 2006; 108:327-32
10. Last accessed 15 September 2009
11. Last accessed 15 September 2009
12. Last accessed 15 September 2009
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14., Last accessed 23 September 2009
15. Last accessed 15 September 2009

FIN09000005 Date of preparation: September 2009