SAN DIEGO – Fingolimod slows brain atrophy in patients with multiple sclerosis and is the only approved drug that does so within the first 6 months of treatment, according to Dr. Jeffrey Cohen of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio.
The findings come from a combined analysis of the drug’s three clinical trials: FREEDOMS (Efficacy and Safety of Fingolimod in Patients With Relapsing-Remitting Multiple Sclerosis) and FREEDOMS II, which pitted 0.5 mg and 1.25 mg daily against placebo for 2 years, and TRANSFORMS (FREEDOMS With Optional Extension Phase), which pitted those doses against weekly intramuscular interferon beta-1a (Avonex) for a year. Brain volumes were assessed by MRI SIENA (structural image evaluation, using normalization, of atrophy) at baseline and 6, 12, and 24 months. More than 3,000 patients 18-55 years old with clinically active relapsing-remitting MS participated.
Dr. Jeffrey Cohen
"There was a consistent" 31%-36% reduction in the rate of brain volume loss with both doses of fingolimod (Gilenya) "as compared to placebo and interferon beta-1a. There was no clear-cut dose effect between the two" doses, said Dr. Cohen, the lead investigator and the director of the Mellen center’s experimental therapeutics program.
In the two trials with placebo arms, fingolimod patients had volume losses of about 0.85%, compared with 1.31% in placebo patients. In the remaining trial, brain volume loss was about 0.31% with fingolimod and about 0.45% with interferon beta-1a.
The "benefit was seen as early as 6 months, in both FREEDOMS and FREEDOMS II. In this analysis of the overall study cohort, there was no apparent early acceleration of brain volume loss, in other words, no pseudoatrophy," Dr. Cohen said at the annual meeting of the American Academy of Neurology.
Other approved MS therapies have shown either no significant effect on brain atrophy or a benefit only in the second year of treatment, as with natalizumab (Tysabri) and glatiramer acetate (Copaxone), he said.
The study investigators found that baseline brain atrophy correlated best with baseline T1 and T2 lesion volume, disability, age, and disease duration and severity. Both high baseline T2 lesion volume and active gadolinium-enhancing T1 lesions predicted brain volume loss during the trial. Volume loss in the study correlated best with worsening disability and increasing numbers of T2 lesions.
The drug seemed to protect brain volume in patients who got it, regardless of baseline characteristics.
There were weak correlations between accumulations of T2 lesions and disability during the study, perhaps because "brain volume and measures of disability don’t change much over 2 years," Dr. Cohen said.
Novartis, the maker of fingolimod, paid for the study. Dr. Cohen disclosed compensation or research support from Novartis, Biogen Idec, Genzyme, Lilly, Serono, and Teva.