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Fingolimod (Gilenya) Fails Pivotal Trial in Primary Progressive MS
The phase III INFORMS trial has failed to show a significant difference between fingolimod (Gilenya, Novartis) and placebo on a combination of disability measures in patients with primary progressive multiple sclerosis (PPMS).
The double-blind, randomized, placebo-controlled, parallel-group study compared the efficacy and safety of fingolimod (0.5 mg) with that of placebo. It was the largest clinical trial ever conducted in patients with PPMS. A total of 970 participants aged 25 to 69 years with PPMS were enrolled in 18 countries, including the U.S., Canada, and the U.K. The patients were treated for at least 3 years.
The study’s primary endpoint was the effect of fingolimod on reducing the risk of 3-month sustained disability progression compared with placebo, based on a composite measure of the Expanded Disability Status Scale, an assessment of upper-limb function (Nine-Hole Peg Test), and walking speed (25-foot Timed Walk Test).
The INFORMS study was based on the knowledge that fingolimod enters the central nervous system (CNS) and can interact with damage-causing cells located in the CNS. It was hypothesized that this central effect, which is well understood in relapsing forms of MS, would also be relevant in PPMS. Compared with the consistently strong efficacy seen in relapsing MS, the results of the INFORMS study appear to suggest that PPMS and relapsing forms of MS have different underlying mechanisms.
Gilenya (fingolimod) is approved in the U.S. for first-line treatment of relapsing forms of MS in adults.
PPMS affects approximately 10% of the 2.3 million patients diagnosed with MS worldwide. PPMS is a distinct disease form, differing from relapsing MS in terms of its basic disease process, the near-absence of acute relapses, and fewer active lesions on magnetic resonance imaging (MRI). The severe, irreversible damage to the CNS in PPMS is thought to be caused by different pathways leading to the loss of nerve cells and a rapid, continuous loss of function over time, which profoundly affects patients’ lives. In addition, the disease is typically diagnosed later than other types of MS, when significant damage to the CNS has already occurred. No approved treatments have been shown to change the course of MS, and management focuses mainly on the treatment of symptoms.
Additional phase III studies of fingolimod are being conducted in two rare diseases: pediatric MS and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
Source: Novartis; December 1, 2014.