New MS Drug-FTY720-immunomodulator

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Novartis Clinical Study Program with FTY720 in MS

Frequently Asked Questions: What is FTY720? What did the Phase II data Show?

FTY720 is a once-daily oral medication with a novel mode of action offering an innovative approach to MS treatment.

Phase II data(i) in patients with relapsing MS showed that:• FTY720 reduced the clinical relapse rate by more than 50 % over six months compared to placebo • Up to 80% reduction in inflammatory disease activity as measured by magnetic resonance imaging (MRI) • Benefits were seen as soon as after two months of treatment and continued to increase over the six month treatment period • Over 90% of patients completed the study suggesting that FTY720 was also well tolerated.

As the relevance of these findings needs to be confirmed in larger scale clinical studies of longer duration, Novartis is currently discussing with regulatory authorities the FTY720 phase III program which is expected to be launched in the fourth quarter of 2005 involving centers in North America and Europe.

Why are these phase II findings noteworthy?• FTY720 has shown a significant and consistent effect on both clinical relapses and MRI measures in just six months. • With its novel mode of action and the added benefit of an oral formulation taken once daily, further clinical development of FTY720 might have a major impact on the way MS will be treated in the future. • Currently marketed MS therapies have only limited clinical effect with an average reduction in relapse rates of about 30% in two year studies. • Furthermore, they require frequent injections ranging from daily to weekly. • The magnitude of benefits shown in this phase II study needs to be confirmed in the larger scale phase III program.

How was the study conducted?• A large double-blind, placebo-controlled, Phase II study was conducted at 32 centers in 11 countries (Europe and Canada).• 281 patients with relapsing MS, the most common form of the disease, were randomized in equal numbers to receive either FTY720 1.25 mg, FTY720 5 mg, or placebo. • The study evaluated the effect of FTY720 on disease activity as measured by MRI and clinical relapses, as well as tolerability and safety of FTY720 over a treatment period of six months.

What side effects were observed?• FTY720 appeared to be generally well tolerated with 92% of patients completing the six-month treatment period. 98% of those patients who completed the six month study volunteered to continue in the ongoing extension phase. • The overall incidence of adverse events was higher in the FTY720 5 mg group compared to the FTY720 1.25 mg and placebo groups. • Most frequently reported adverse events were related to non-serious infections (such as colds), gastrointestinal disorders (such as diarrhea and nausea), nervous system disorders (such as headaches) and respiratory disorders (such as short breath and cough). • The relevance of these findings need to be confirmed in larger scale phase III clinical studies of longer duration.

How is FTY720 thought to work?• FTY720 is a once-daily oral medication with a novel mode of action offering a innovative approach to MS treatment. It is the first sphingosine-1-phosphate (S1P) receptor modulator.• FTY720 differs from currently approved treatments because it is the only medication that binds the receptors of S1P, present on the surface of lymphocytes, which are a subpopulation of white blood cells. • In MS, lymphocytes circulating in the central nervous system (e.g. the brain and spinal cord) attack the myelin sheath that surrounds and protects nerve fibres (axons) which are responsible for transmitting nerve signals to other parts of the body. • As a consequence of receptor binding, the lymphocytes can no longer respond to the molecule that signals them to circulate to sites of inflammation in the body and they stay in the lymph nodes.• However, the lymphocytes remain functional and may still be activated within the lymph nodes as part of the immune response.

Where has this data been presented?• The FTY720 phase II data has been presented at the 15th European Neurological Society (ENS) meeting in Vienna, June 21, 2005.• For more details, please refer to congress abstract (enclosed)• The data will be submitted for publication in a peer review journal shortly.

(i) FTY720 in relapsing MS: Results of a double blind placebo controlled trial with a novel oral immunomodulator. Clinical Abstract of data presented at the 15th European Neurological Society meeting, Vienna, June 18-22, 2005.

Please also watch the related article: FTY720 in relapsing MS: Results of a double blind placebo controlled trial with a novel oral immunomodulator

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