New data will be presented at the 64th annual meeting of the American Academy of Neurology (AAN) that support the efficacy and safety profile of Gilenya® (fingolimod), the only oral therapy approved to treat relapsing forms of multiple sclerosis (MS).
Novartis will also showcase new data on its investigational compound BAF312 (siponimod), a selective modulator of the S1P receptor subtypes 1 and 5 (S1P1, -5R modulator) in its multiple sclerosis portfolio.
“The data being presented reinforce our confidence in the sustained efficacy and safety profile of Gilenya,” said David Epstein, Head of the Pharmaceuticals Division of Novartis Pharma AG.
“We also are pleased to present encouraging data for our investigational compound BAF312 (siponimod). The clinical development of BAF312 demonstrates our commitment to developing new therapeutic options for the MS community.”
Results from the Phase III FREEDOMS extension study showed significant improvements in clinical and MRI measures in patients who switched from placebo (administered during the 24-month core study) to Gilenya (administered during the extension).
Overall, 1033 patients completed the two-year, double-blind FREEDOMS core study, of whom 90% completed three years observation and 45% were followed for four years in this study before being transferred to the umbrella follow-up study (LONGTERMS).
Patients who switched from placebo to Gilenya saw a 55% decrease in their annualised relapse rate (ARR) during the extension phase compared to the core phase (ARR [core] = 0. 29 vs. ARR [extension] 0.13; p<0.001).
Significantly more patients on continuous fingolimod treatment compared to those first randomised to placebo remained relapse-free (59% vs. 37%) and free from three-month confirmed disability progression (74 % vs. 66 %).
MRI measures continued to show significant effects in favor of fingolimod treatment, including a significantly reduced rate of brain atrophy in the patients treated continuously as compared to switch patients (mean (%) change in brain volume -1.67% vs. -2.24%; p = 0.001) at the end of the observation. In the core FREEDOMS study, Gilenya reduced the rate of brain atrophy by 38% versus placebo at two years (0-24 months).
The phase III FREEDOMS extension showed a safety profile consistent with that of the pivotal phase III trials. The most common adverse events were nasopharyngitis, low lymphocyte counts (to be expected from the mode of action), upper respiratory tract infections and influenza-.
“This extension study confirms the efficacy shown in the published phase III studies and supports the positive long term impact of continuous treatment. The favorable longer term safety profile is consistent with results from the phase III studies,” said Ludwig Kappos, Department of Neurology, University of Basel, Switzerland. “These observations in a large group of patients, now for four and more years, confirm that fingolimod is a valuable treatment option for patients with relapsing remitting MS.”
Additionally, new data for up to 7 years of treatment from the phase II extension study demonstrated patients treated with Gilenya (n=122) had sustained low MRI and clinical disease activity. The overall ARR for the continuous Gilenya treatment group was 0.16, which can be expressed as one relapse every 6 years. Of patients on continuous Gilenya treatment since study start and who completed the long-term extension, over half had remained free of relapses throughout the study.
The phase III registration program for Gilenya included the two-year FREEDOMS study and a head-to-head study in which Gilenya showed a 52% relative reduction in annualized relapse rate (primary endpoint) compared to Avonex® (interferon-beta-1a IM), a commonly prescribed treatment, at one year.
Low incidence of ECG abnormalities and symptomatic heart rate reduction at treatment initiation in 2,400 patient FIRST Study
New data from the large, 4-month, open-label, single-arm multi-center FIRST study demonstrate an overall low incidence of significant first dose bradycardia [i.e. 1.3% of patients experienced bradycardia < 45 bmp and no patient experienced a heart rate <30 bpm] and conduction abnormalities at treatment initiation with Gilenya.
Importantly, this study provides data on continuous ECG monitoring by ambulatory Holter Electrocardiogram (ECG) for six hours following the administration of the first dose to identify any heart rate or ECG abnormalities.
Results from more than 2,400 patients showed the incidence of Mobitz I second degree atrioventricular blocks (AVBs) was 1.4% at the post-dose Holter ECG for 6 hours after administration, and the incidence of Mobitz II second degree, or 2:1 AVBs was 0.5%.
The short-term safety profile of Gilenya in the FIRST study was generally consistent with that observed in the phase III studies. This included the low incidence of the known cardiac effects of fingolimod at treatment initiation (typically transient decreases in heart rate and generally asymptomatic atrioventricular blocks).