New phase III results presented at the American Academy of Neurology (AAN) congress show that 80-83% of patients taking FTY720 (fingolimod), an investigational oral compound for relapsing-remitting multiple sclerosis, remained free of relapses during the one-year study compared to 69% of those on interferon beta-1a, an established standard of care (p<0.001).
These data reinforce previous results from the TRANSFORMS study announced in December 2008 showing that the relapse rate at one year was 52% lower in patients taking FTY720 0.5 mg than with interferon beta-1a, or Avonex (0.16 vs. 0.33 respectively).
The relapse rate with FTY720 1.25 mg was 38% lower than with interferon beta-1a (0.20 vs. 0.33, both p<0.001).
Full results will be submitted to a peer-reviewed journal in the next few months, with regulatory submissions planned in the US and EU at the end of 2009.
“TRANSFORMS is the first phase III clinical trial to show that oral fingolimod may provide patients with an alternative choice to currently available medications for treating relapsing-remitting multiple sclerosis,” said Jeffrey Cohen, MD, lead investigator of the TRANSFORMS study and staff physician at the Cleveland Clinic Mellen Center for Multiple Sclerosis Treatment and Research in Cleveland, Ohio, USA.
Also presented at AAN were longer-term results from an ongoing open-label Phase II extension study (n=155).
This showed continued low relapse rates after four years of treatment with FTY720, with no significant change in the safety profile from three to four years.
In TRANSFORMS, FTY720 was generally well-tolerated with 87% of FTY720 patients completing the study on treatment. The most commonly reported adverse events, seen in more than 10% of patients in all three study arms, were headache, nasopharyngitis and fatigue.
Adverse events seen in FTY720-treated patients in TRANSFORMS included transient reductions in heart rate at the start of treatment, small increases in blood pressure on average, elevations in liver enzymes (also seen with interferon beta-1a), and a small number of cases of macular edema.
In terms of serious adverse events, infections, bradycardia and atrioventricular block, malignancies and dyspnea were reported in less than 2% of FTY720-treated patients.
Following the preliminary release of data in December 2008, a patient who had discontinued FTY720 treatment in August 2008 died from aspiration pneumonia related to a progressive neurological condition in February 2009.
The exact nature of the underlying diagnosis is unclear, but viral testing has proved negative, including testing for progressive multifocal leukoencephalopathy (PML).
A role for FTY720 could neither be confirmed nor excluded. In general, the safety profile of the FTY720 0.5 mg dose appeared to be better than that of the 1.25 mg dose.