`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Bettina Maunz
`Novartis Pharma Communications
`+41 61 324 7996 (direct)
`+41 79 593 4278 (mobile)
`bettina.maunz@novartis.com
`
`
`
`
`Novartis International AG
`Novartis Communications
`CH-4002 Basel
`Switzerland
`http://www.novartis.com
`
`
`
`
`Corinne Hoff
`Novartis Global Media Relations
`+41 61 324 9577 (direct)
`+41 61 324 2200 (main)
`corinne.hoff@novartis.com
`
`
`
`
`MEDIA RELEASE • COMMUNIQUE AUX MEDIAS • MEDIENMITTEILUNG
`
`
`Phase II data for FTY720 shows sustained efficacy and good tolerability over 18
`months in patients with relapsing multiple sclerosis (MS)
`
`MS is the leading cause of neurological disability in young adults – high unmet need for effective
`and convenient therapies
`
`Basel, April 6, 2006 – Data from the extension of a Phase II study to 18 months support the
`significant effects of FTY720 (fingolimod), a novel once-daily oral compound in development for
`treatment of relapsing-remitting multiple sclerosis (MS). More than two million people worldwide are
`estimated to suffer from MS, which is the leading cause of neurological disability in young adults1
`and affects twice as many women as men.
`
`The data, presented at the American Association of Neurology (AAN) meeting, showed that both
`patient groups taking FTY720 (1.25 mg and 5 mg) who had experienced more than a 50% reduction
`in their annualized relapse2 rate during the study’s first six months compared to placebo maintained
`this low relapse rate during the subsequent 12-month extension.
`
`Currently marketed MS therapies afford an average reduction in relapse rates of only 30% in two-year
`studies and require frequent injections ranging from daily to weekly3,4,5,6 .
`
`In patients who switched from placebo to either the 1.25 mg or 5 mg dosing of FTY720 after six
`months, the annualized relapse rate was reduced to a similar extent during the subsequent twelve-
`month extension phase of the study compared to the first six months on placebo. At month 18,
`Magnetic Resonance Imaging (MRI) scans were performed in a subgroup of patients. Consistent with
`what was seen in MRI scans at month six, the vast majority of patients were free from lesions
`showing active inflammation at month 18.
`
`“We are very encouraged to see that the effects of fingolimod in significantly reducing both clinical
`relapses and inflammatory disease activity are maintained over 18 months,” said Dr. Paul O’Connor,
`MD, St. Michael’s Institute, Toronto, Canada. “We hope that the magnitude of benefits shown in the
`Phase II study can be confirmed in the larger-scale Phase III study program, which is currently being
`initiated.”
`
`The most frequently reported adverse events in patients treated up to 18 months were non-serious
`infections (colds, influenza) and headache. Effects initially seen in the first six months of treatment
`(i.e. first dose heart rate reduction, increase in blood pressure, alteration in liver function, mild
`increase in airway resistance) did not appear to progress with continued dosing beyond six months.
`There were also no unexpected safety findings during the extension phase compared to the six-month
`placebo-controlled phase. All patients in the extension study are now continuing with the 1.25 mg
`dose since both the 5 mg dose, which had a higher rate of adverse events, and 1.25 mg doses were
`equally effective in reducing disease activity.
`
`1/4
`
`Apotex v. Novartis
`IPR2017-00854
`NOVARTIS 2072
`
`

`

`
`Phase II study design
`The results are from a large Phase II study conducted at 32 centers in 11 countries (Europe and
`Canada). In the initial, placebo-controlled part of this study, 281 patients were randomized in equal
`numbers to receive either placebo, 1.25 mg or 5 mg of FTY720 orally once-daily for six months. The
`study evaluated the effect of FTY720 on disease activity as measured by MRI and clinical relapses as
`well as its tolerability and safety. After six months, patients had the option to enter the extension
`phase evaluating the longer-term effects. Patients in the placebo group were re-randomized to receive
`either 1.25 mg or 5 mg, while patients already on FTY720 continued their originally-assigned
`treatment. Having completed the 12 month time point, the 5 mg dose arm was discontinued and
`patients previously receiving this dose were continuing in the study on a dose of 1.25mg.
`
`Analysis of the 24-month data is expected to be presented at a key neurological congress in the second
`half of 2006.
`
`Phase III study program
`Novartis has initiated its first Phase III pivotal study called “FREEDOMS” (Fingolimod Research
`Evaluating Effects of Daily Oral therapy in Multiple Sclerosis). The 24-month, randomized, double-
`blind, placebo-controlled FREEDOMS study will include more than 1,000 patients with relapsing-
`remitting MS between age 18-55. Study participants will be equally randomized to either receive
`either 1.25 mg or 0.5 mg of FTY720 or placebo once daily for up to 24 months.
`
`This study has begun enrolling patients in several European countries. Novartis is currently in
`discussions with the US Food and Drug Administration (FDA) on Phase III initiation in the US.
`
`“Oral fingolimod has a novel mode of action different from all available MS therapies. If the Phase III
`clinical program confirms the promise of the Phase II results, oral fingolimod could represent a major
`improvement in the way MS will be treated in the future,” said chief investigator Professor Ludwig
`Kappos, MD, Department of Neurology at the University Hospital in Basel, Switzerland.
`
`About FTY720 (fingolimod)
`FTY720 binds to the sphingosine 1-phosphate receptor-1 (S1P1) on a proportion of circulating
`lymphocytes and reversibly traps them in the lymph nodes. As a result, FTY720 lowers the number of
`activated T-cells circulating to the blood stream and central nervous system (CNS), which reduces
`neuroinflammation and myelin damage in the brain and spinal cord. Under FTY720 treatment, many
`components of normal lymphocyte function are unaffected and can be activated as part of the immune
`response within the lymph nodes and other tissues. FTY720 has been developed by Novartis Pharma
`and licensed from Mitsubishi Pharma Corporation.
`
`About Multiple Sclerosis
`MS is the most common inflammatory and neurodegenerative disorder of the central nervous system,
`including the brain, spinal cord and optic nerves7. MS typically presents itself in relapsing forms. The
`relapsing-remitting (RRMS) course is the most common form of the disease. Patients suffer acute
`self-limiting attacks (relapses) of neurological dysfunction followed by complete or incomplete
`remission in function. Over time, transmission of electrical nerve impulses is disrupted, nerve cells are
`destroyed, and patients experience symptoms ranging from fatigue, tingling, numbness and blurred
`vision to poor muscle control with partial or complete paralysis, speech or mental impairment. About
`50% of patients advance to the secondary progressive (SPMS) course within 10 years8.
`
`2/4
`
`

`

`
`This release contains certain forward-looking statements relating to Novartis’ business, which can be
`identified by the use of forward-looking terminology such as “encouraged”, “hope”, “expected”,
`“will”, “could”, or similar expressions, or by express or implied statements regarding the potential
`long-term impact of a patient’s use of fingolimod, the potential commencement of Phase III studies of
`fingolimod in the US, the potential regulatory approval of fingolimod in any jurisdiction, or potential
`future revenue from fingolimod. 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 fingolimod to be materially different from any future results,
`performance or achievements expressed or implied by such statements. There can be no guarantee
`that Phase III studies of fingolimod will be permitted to commence in the US, or that fingolimod will
`be approved for any indications or labeling in any market. Nor can there be any guarantee of potential
`future sales of fingolimod. Neither can there be any guarantee regarding the long-term impact of a
`patient's use of fingolimod. In particular, management's expectations regarding fingolimod 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; Novartis’ ability to obtain or maintain patent or other proprietary intellectual
`property protection; competition in general; 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. 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 these disorders.
`
`Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, treat disease and
`improve well-being. Our goal is to discover, develop and successfully market innovative products to
`treat patients, ease suffering and enhance the quality of life. Novartis is the only company with
`leadership positions in both patented and generic pharmaceuticals. We are strengthening our
`medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven
`pharmaceuticals, high-quality and low-cost generics and leading self-medication OTC brands. In
`2005, the Group’s businesses achieved net sales of USD 32.2 billion and net income of USD 6.1
`billion. Approximately USD 4.8 billion was invested in R&D. Headquartered in Basel, Switzerland,
`Novartis Group companies employ approximately 91,000 people and operate in over 140 countries
`around the world. For more information, please visit http://www.novartis.com.
`
`
`3/4
`
`

`

`
`References
`1 Multiple Sclerosis International Federation (http://www.msif.org/en/ms_the_disease/quick_facts.html)
`2 A relapse refers to the appearance of new symptoms or the aggravation of old ones, lasting for at least 24 hours.
`3
`PRISMS study group. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing-remitting
`multiple sclerosis. The Lancet 1998; Vol 352: 1498-1504.
`4 LD Jacobs et al. Intramuscular Interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol
`1996, 39: 285-294.
`IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I.
`Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 1993; 43: 655-661.
`6 K.P. Johnson et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis:
`Results of a phase III multicenter, double-blind, placebo-controlled trial. Neurology 1995; 45: 1268-1276.
`7 Multiple Sclerosis International Federation (http://www.msif.org/en/ms_the_disease/index.html)
`8 Weinshenker BG. Natural history of multiple sclerosis. Ann Neurol 1994, 36: S6-S11.
`
`
`5
`
`###
`
`
`Media contacts
`
`Bettina Maunz
`Novartis Pharma Communications
`+ 41 61 324 7996 (direct)
`+ 41 79 593 4278 (mobile)
`bettina.maunz@novartis.com
`
`Corinne Hoff
`Novartis Global Media Relations
`+41 61 324 9577 (direct)
`+41 61 324 2200 (main)
`corinne.hoff@novartis.com
`
`
`
`
`4/4
`
`