The data, presented at the ECTRIMS/ACTRIMS meeting in Thessalonica, Greece, showed that both patient groups taking FTY720 (1.25 mg and 5 mg) who had experienced a reduction in their annualized relapse rate of more than 50% during the first six months of the study compared to placebo maintained this low relapse rate during the subsequent six-month extension.
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 by at least 70% during the second six-month study phase compared to the first six months on placebo.
More than 80% of patients who received FTY720 for up to 12 months were free from lesions showing active inflammation on magnetic resonance imaging (MRI) at month twelve irrespective of their FTY720 treatment dose (1.25 mg or 5 mg).
"We are excited by these full-year study results confirming the significant effect of oral FTY720 on reducing both clinical relapses and inflammatory disease activity that we first saw during the six-month placebo-controlled phase of the study," said chief investigator Professor Ludwig Kappos, MD, Department of Neurology at the University Hospital in Basel, Switzerland, "We hope that the magnitude of benefits shown in Phase II will be confirmed in the larger scale Phase III study program expected to be launched soon." Based on the positive Phase II study results, Novartis is in discussions with regulatory authorities about the FTY720 Phase III program, which is expected to be launched by the end of 2005.
Over two million people worldwide are estimated to suffer from multiple sclerosis, which is the leading cause of neurological disability in young adults. MS is the most common chronic, disabling disease of the central nervous system affecting twice as many women than men.3 MS has a significant impact on the patient's social activities, employment and overall quality of life. Currently marketed MS therapies afford an average reduction in relapse rates of 30% in two-year studies and require frequent injections ranging from daily to weekly. , , ,
FTY720 Phase II study results
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 5.0 mg 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 in the placebo group were re-randomized to receive either FTY720 1.25 mg or 5 mg blinded for an additional six months, while patients already on FTY720 continued their originally-assigned treatment. A total of 98% of the 255 patients who completed the first six months volunteered to continue in the extension phase evaluating the longer-term effects of FTY720.
In the 12-month analysis, both patient groups on FTY720 (1.25 mg and 5 mg) who had experienced a reduction in their annualized relapse rate of more than 50% during the first six months compared to placebo maintained this low relapse rate during the subsequent six-month extension. In those patients who switched from placebo to either 1.25 mg or 5 mg of FTY720 after six months, the annualized relapse rate was reduced by at least 70% during the second six-month study phase compared to the first six months on placebo.
The MRI results at 12 months showed low levels of inflammatory disease activity in all FTY720 groups. In patients who switched from placebo to FTY720, the mean number of inflammatory (Gd-enhancing) lesions on MRI (at the 12th month) was reduced by more than 80% compared to the sixth month. More than 80% of patients who received FTY720 for up to 12 months were free from lesions showing active inflammation on MRI at the 12th month irrespective of their FTY720 treatment dose (1.25 mg or 5 mg).
FTY720 appeared to be well tolerated, with 91% of patients who entered the extension phase completing the 12th month on the study drug. There were no unexpected safety findings during the extension as compared to the six-month placebo-controlled phase. The most frequently reported adverse events in patients treated up to twelve months were non-serious infections (colds, influenza), headache, diarrhoea and nausea.
About FTY720
Oral FTY720 has a novel mode of action different from all available therapies. It reversibly sequesters lymphocytes away from blood and susceptible target organs such as the central nervous system (CNS), thereby reducing neuroinflammation in MS. 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 nerves. 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 years.
This release contains certain forward-looking statements relating to Novartis' business, which can be identified by the use of forward-looking terminology such as "suggest", "expected to be launched", "will be confirmed" or similar expressions, or regarding 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. Nor can there be any guarantee of potential future sales of FTY720. Neither can there be any guarantee regarding the long-term impact of a patient's use of FTY720. In particular, management's expectations regarding commercialization of FTY720 could be affected by, among other things, unexpected clinical trial 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 pharmaceuticals and consumer health. In 2004, the Novartis group of companies' businesses achieved sales of USD 28.2 billion and pro forma net income of USD 5.8 billion. The group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis group companies employ about 83,700 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
References
21st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)/10th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS)
A relapse refers to the appearance of new symptoms or the aggravation of old ones, lasting for at least 24 hours.
Multiple Sclerosis International Federation (http://www.msif.org/en/ms_the_disease/quick_facts.html)
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.
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.
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.
L. Kappos et al. Promising results with a novel oral immunomodulator – FTY720 – in relapsing MS. Clinical Abstract of data presented at the 21st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)/10th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) meeting, Thessalonica, Greece, Sept 28-Oct 1, 2005.
P. O’Connor et al. Phase II study with oral FTY720 in relapsing MS: Results of the dose-blinded active drug extension phase at 12 months. Clinical Abstract of data presented at the 21st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)/10th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) meeting, Thessalonica, Greece, Sept 28-Oct 1, 2005.
Multiple Sclerosis International Federation (http://www.msif.org/en/ms_the_disease/index.html)
Weinshenker BG. Natural history of multiple sclerosis. Ann Neurol 1994, 36: S6-S11.
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