Fingolimod (which, by the way, wins our award for Most Unintentionally Humorous Drug Name) works by keeping the immune system''''s T cells in the lymph nodes and away from the central nervous system, which is for reasons yet unknown, vulnerable to attack in an MS patient.

The trial enrolled over 250 patients. In the first six months, patients were randomized to receive either one of two doses of fingolimod, or a placebo. For the following six months, all the placebo patients were randomized to one of the two fingolimod doses.

The results...

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...showed that disease activity, measured by magnetic resonance imaging or MRI, was reduced by up to 80% compared to placebo, and the rate of relapses dropped by 50%. Patients who continued fingolimod in the following six months maintained the lowered relapse rate, and patients who were switched from placebo to fingolimod dropped their relapse rate by at least 70%.

"These results demonstrate that once-daily oral FTY720 provides a significant and rapid improvement in MRI measures of inflammation, as well as in relapse-related clinical endpoints in patients with relapsing multiple sclerosis," said Chief Investigator Professor Ludwig Kappos, MD, of the Department of Neurology at the University Hospital in Basel, Switzerland. "If the magnitude of benefits shown in this Phase II study are confirmed in the larger-scale Phase III study program, oral FTY720 could represent a major improvement in the way MS will be treated in the future."

Of paramount concern after the Tysabri-PML situation, the safety profile of FTY720 seems relatively mild at this stage (recall that so did Tysabri''''s when it was in Phase II and III). Most common adverse affects had to to do with respiratory infections and GI issues. There were also increases in liver enzyme activity and blood pressure, though these were asymptomatic. A close eye will certainly be kept on these parameters during Phase III.

Speaking of which, the Phase III study, called FREEDOMS, is massive. It includes over 100 study centers and will ultimately enroll over 2,000 patients worldwide in a 2 year trial.

Yes, 2 years and "currently enrolling" means that the minimum time to market for Fingolimod should be approximately 3 years from now, placing us in 2009. Certainly, this tempers the excitement about this drug for the time being, but it is always encouraging to see a promising therapy progressing to the final stage of trials-- and in this case, potentially delivering the benefit of a once-daily oral therapy with a limited side effect profile and potent disease modifying abilities.

Press Release

Phase 2 Data Showing Clinical Benefits of Novel Once-Daily Oral Multiple Sclerosis Therapy FTY720 (Fingolimod) Published in New England Journal of Medicine

* One-year data show significant reductions in inflammatory disease activity and clinical relapse activity with daily oral FTY720 were for up to one year

* Phase III program investigating FTY720 now being implemented in the U.S.

* Approximately 400,000 people in the U.S. suffer from multiple sclerosis, which is one of the leading causes of neurological disability in young adults

EAST HANOVER, NJ -- September 14, 2006 -- Clinical trial results published in the New England Journal of Medicine showed that FTY720 (fingolimod), a novel once-daily oral compound, demonstrated significant benefits in the treatment of various relapsing forms of multiple sclerosis (MS).

Based on the positive phase 2 study results, Novartis has launched a Phase III pivotal study program to further evaluate FTY720''''s benefits in patients with the relapsing-remitting form of multiple sclerosis (RRMS).

The Phase II data show that during the initial six months of treatment, oral FTY720 taken once-daily reduced the rate of inflammatory disease activity, measured by magnetic resonance imaging or MRI, by up to 80% compared to placebo and also reduced the rate of clinical relapses by more than 50%. In patients who continued FTY720 treatment during the subsequent six-month extension, low levels of disease activity were maintained as measured by both MRI and relapses, and both these measures decreased in patients who switched from placebo to FTY720.

"These results demonstrate that once-daily oral FTY720 provides a significant and rapid improvement in MRI measures of inflammation, as well as in relapse-related clinical endpoints in patients with relapsing multiple sclerosis," said Chief Investigator Professor Ludwig Kappos, MD, of the Department of Neurology at the University Hospital in Basel, Switzerland. "If the magnitude of benefits shown in this Phase II study are confirmed in the larger-scale Phase III study program, oral FTY720 could represent a major improvement in the way MS will be treated in the future."

The recently launched global Phase III pivotal study program called FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis) will include over 100 study centers and over 2,000 patients worldwide with RRMS. The randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of two orally-administered doses of FTY720 (1.25 mg and 0.5 mg) as compared to placebo in reducing the frequency of relapses in patients treated for up to 24 months. Other objectives include evaluation of efficacy on disability progression, Magnetic Resonance Imaging (MRI) lesion parameters as well as safety and tolerability of FTY720 (1.25 mg and 0.5 mg) compared to placebo.

Phase 2 Study Results

The Phase II study described in the New England Journal of Medicine was conducted at 32 centers in 11 countries (in Europe and Canada) to evaluate the effect of FTY720 on disease activity as measured by MRI and relapses as well as its safety and tolerability.

In the initial placebo-controlled phase, 281 patients were randomized equally to receive FTY720 1.25 mg, FTY720 5 mg or placebo once-daily for six months. Of the 255 patients who completed this part of the study, 98% volunteered to continue in the extension phase. Patients in the placebo group were then re-randomized to receive either FTY720 1.25 mg or 5 mg blinded for an additional six months, while those already on the study drug continued with their original treatment.

This study showed that once-daily oral FTY720 provides significant improvement in MRI measures of inflammation and in relapse-related clinical endpoints in patients with relapsing MS. Inflammatory disease activity as measured by the total *****ulative number of gadolinium (Gd)-enhancing MRI lesions was significantly reduced by up to 80% (P In both the groups taking FTY720 (1.25 mg or 5 mg), patients who had experienced a reduction in their annualized relapse rate of more than 50% compared to placebo during the first six months of the study maintained this low relapse rate during the subsequent six-month extension study.

In patients who switched from placebo to either dosage of FTY720 after six months, the annualized relapse rate was reduced by at least 70% during the six-month extension study compared to the period on placebo.

Relapse rates were reduced by 55% in the FTY720 1.25 mg group (P =.009) and by 53% in the FTY720 5 mg group (P =.014) compared to placebo. Time to first confirmed relapse was also significantly prolonged in both FTY720 groups compared to placebo (P =.007 in FTY720 1.25 mg, P =.01 in FTY720 5 mg). More than 80% of patients who received FTY720 for up to 12 months were free from lesions showing active inflammation on MRI at month 12, irrespective of their treatment dose.

In the six-month placebo-controlled phase of the 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 flow. Clinically asymptomatic increases in alanine aminotransferase (liver enzyme) and increase in blood pressure were also observed. There were no unexpected safety findings during the six-month extension phase as compared to the six-month placebo-controlled phase. The ongoing Phase III study program includes comprehensive safety monitoring which will provide further assessment of the safety profile.

An analysis of two-year phase II data with FTY720 will be presented at the European Congress for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Madrid later this month.

About FTY720 and Multiple Sclerosis

FTY720 is the first in a new class of disease-modifying treatments called sphingosine 1-phosphate receptor (S1P-R) modulators and has a novel mode of action different from all currently marketed MS therapies. FTY720 has been developed by Novartis and licensed from Mitsubishi Pharma Corporation.

More than two million people worldwide are estimated to suffer from MS, which is one of the leading causes of neurological disability in young adults. It is the most common inflammatory and neurodegenerative disorder of the central nervous system, including the brain, spinal cord and optic nerves.

The symptoms of MS can range from tingling, numbness, pain, slurred speech and blurred or double vision, to muscle weakness, poor balance or coordination, and tremors. These symptoms can have a significant impact on the patient''''s employment, social activities and overall quality of life.

SOURCE: Novartis Pharmaceuticals Corporation