Date: 2012-06-11
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 22nd Annual Meeting of the European Neurological Society (ENS)
Company: Novartis (Switzerland)
Product: Gilenya® (fingolimod)
Action
mechanism: Gilenya®, licensed from Mitsubishi Tanabe Pharma Corporation, is the first in a new class of drugs called sphingosine 1-phosphate receptor (S1PR) modulators. In multiple sclerosis, the immune system damages the covering that protects nerve fibers in the central nervous system which includes the brain and spinal cord. Fingolimod reduces the ability of T cells to move from the lymph nodes towards the brain and spinal cord thus limiting the damage they cause in multiple sclerosis. It does this by blocking the action of a receptor on the T cells called the sphingosine-1-phosphate receptor, which is involved in regulating the movement of these cells in the body.
Disease: relapsing-remitting multiple sclerosis
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
Country:
Trial
details: TRANSFORMS was a large phase III double-blind, double-dummy, head-to-head study that involved 1,292 patientswith relapsing-remitting MS that was conducted over one year, comparing the efficacy and safety of Gilenya® to interferon-beta-1a IM. At the end of the 12-month core study, eligible patients could enroll in the extension study, which ran for an additional 3.5 years. Patients on once-daily oral Gilenya® remained on drug and those who had been treated with interferon-beta-1a (IM) switched to Gilenya® for the duration of the extension study.
Latest
news: New long-term data for Gilenya® (fingolimod), the only oral therapy approved to treat people with relapsing forms of multiple sclerosis, show a sustained efficacy benefit and a consistent safety profile with up to 4.5 years of continuous treatment. These results, from an extension of the phase III head-to-head TRANSFORMS study, also showed improved efficacy for patients switched to Gilenya from Avonex® (interferon-beta-1a IM), a commonly prescribed MS treatment.
In the core TRANSFORMS study, Gilenya® demonstrated superior efficacy to interferon-beta- 1a IM, reducing the annualized relapse rate (ARR) by 52% at one year (Gilenya® 0.5 mg, ARR = 0.16; interferon-beta- 1a IM, ARR = 0.33; p<0.001). The extension study showed that this low relapse rate was sustained in patients receiving continuous treatment with Gilenya® (n=356) for up to 4.5 years (Gilenya 0.5 mg, ARR core study = 0.16; ARR extension study = 0.16). The data from the extension study also showed that patients treated with Gilenya® continuously maintained a low brain atrophy rate throughout the study as measured by assessing brain volume loss, which is valued as a predictor of long-term disability.
For patients who switched to Gilenya® for the open-label extension study (n=167), their ARR was 0.33 in the core study when treated with interferon-beta-1a IM and 0.20 in the extension phase when treated with Gilenya® (n.s.). Patients in the switch group also displayed a slowing of brain atrophy following the switch to Gilenya®.
These extension data from up to 4.5 years also showed long-term treatment with Gilenya® was generally well tolerated with a safety profile consistent with pivotal trials. In line with previous studies, including the core TRANSFORMS study, the most common adverse events were nasopharyngitis, headache, and upper respiratory tract infections. Switching therapy from IFN beta-1a to Gilenya® did not reveal any new or unexpected safety concerns. On treatment initiation, a low incidence of asymptomatic transient bradycardia was observed in patients who switched from interferon-beta-1a IM to Gilenya (IFN-0.5 mg [0.6%]), which resolved without treatment. Overall cardiac events were similar across all patient groups.
In addition, all patients treated with Gilenya in the extension phase, regardless of original treatment in the core study, showed comparable percentage of patients free from MRI disease activity by the end of the study. (Free from Gd enhanced T1 lesions: 77.4% in switch group vs. 74.7% Gilenya 0.5mg; Free from new/newly enlarged T2 lesions: 45.0% in switch group vs. 42.0% Gilenya 0.5mg). The continuous and switch groups did not significantly differ with respect to disability progression at the end of the study.
