Some news on FTY720 - further data to be presented at the end of the month.
Phase II 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 maintained for up to one year
* Phase III program investigating FTY720 now being implemented in the U.S.
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 II 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 randomised, 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 II 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 randomised 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-randomised 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 cumulative number of gadolinium (Gd)-enhancing MRI lesions was significantly reduced by up to 80% (p<0.001 in FTY720 1.25 mg, p<0.006 in FTY720 5 mg) compared to placebo over six months of treatment. At six months, the proportion of patients free of Gd-enhancing lesions was also greater in both FTY720 groups compared to placebo (p<0.001 for both groups) with a separation between the curves becoming evident from two months onwards.
In both the groups taking FTY720 (1.25 mg or 5 mg), patients who had experienced a reduction in their annualised 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 annualised 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=0.009) and by 53% in the FTY720 5 mg group (p=0.014) compared to placebo. Time to first confirmed relapse was also significantly prolonged in both FTY720 groups compared to placebo (p=0.007 in FTY720 1.25 mg, p=0.01 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.
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.
Source: Novartis Pharmaceuticals Corporation