Reducing risk of MS disability progression

MANILA, Philippines -  A new analysis demonstrated that fingolimod reduced the risk of disability progression in patients with relapsing-remitting multiple sclerosis (RRMS), regardless of treatment history.

This analysis of the Phase III two-year FREEDOMS study is one of 11 abstracts on fingolimod presented at the 63rd annual meeting of the American Academy of Neurology (AAN).

“In developing fingolimod, Novartis initiated a large clinical trial program that would provide the MS community with robust data to define the efficacy and safety profile of this oral treatment for relapsing forms of MS,” said Dr. Trevor Mundel, global head of development at Novartis Pharma AG.

“Our scientific presence at AAN is evidence of our commitment to continued research and ongoing reporting of clinical information to physicians and patients,” Mundel added.

The primary endpoint for the two-year FREEDOMS study was relapse rate, in which fingolimod reduced relapses by 54 percent compared to placebo (p<0.001).

In a key secondary endpoint, fingolimod showed 30 percent reduction (p<0.05) in the risk of three-month confirmed disability progression as compared to placebo over two years. 

The FREEDOMS analysis showed that 0.5 mg fingolimod-treated patients who were new to therapy (n = 493) had 37 percent reduction in the risk of three-month confirmed disability progression compared to placebo (HR: 0.63; 95% CI: 0.41-0.95) while those previously treated with alternate therapies (n = 350) fingolimod 0.5 mg led to 30 percent reduction in risk (HR: 0.70; 95% CI: 0.43-1.14).

Consistent favorable effects on disability progression were observed for Gilenya-treated patients compared to placebo for subgroups defined by age, gender, and disease severity as defined by EDSS score, relapse activity prior to study, magnetic resonance imaging (MRI) lesion burden or lesion activity at the time of the start of the study.  

“These data provide deeper insights into the effect of fingolimod in significantly reducing MS disability progression across the broad range of patient subpopulations that this analysis evaluated,” said Dr. Virginia Devonshire, director of the University of British Columbia MS Clinic and a FREEDOMS trial investigator.

Fingolimod, licensed from Mitsubishi Tanabe Pharma Corp., is the first oral treatment in a new class of drugs called sphingosine 1-phosphate receptor (S1PR) modulators.

Approved in more than 35 countries including the United States, Canada and Germany, fingolimod has been studied in Phase III clinical trials of over 2500 patients with relapsing-remitting MS. 

In MS, the immune system damages the myelin sheath that protects nerve fibers in the central nervous system (CNS), which includes the brain and spinal cord.

As shown in animal models, fingolimod stops many of the white blood cells (lymphocytes) from leaving the lymph nodes.

Exactly how fingolimod works in MS is unknown, but it is thought that it results in fewer white blood cells entering the CNS to attack and damage the myelin sheath.

If fingolimod treatment is stopped for any reason, the number of white blood cells circulating in the body increases over the first few days and gradually returns to normal within one to two months.

The most common side effects are headache, liver enzyme elevations, influenza, diarrhea, back pain, and cough.

Other fingolimod-related side effects include transient, generally asymptomatic, heart rate reduction and atrioventricular block upon treatment initiation, mild blood pressure increase, macular edema, and mild bronchoconstriction.

The rates of infections overall, including serious infections, were comparable among treatment groups, although a slight increase in lower respiratory tract infections (primarily bronchitis) was seen in patients treated with fingolimod.

The number of malignancies reported across the clinical trial program was small, with comparable rates between the fingolimod and control groups.

While there is still much to be understood about multiple sclerosis, it is thought to be an autoimmune disease of the central nervous system that is chronic, progressive and often disabling.

It affects over 400,000 Americans and more than 2.1 million people worldwide. The most common forms of the disease, relapsing forms of MS, are characterized by exacerbations or flare-ups interspersed with periods of disease remission.

Typically, MS strikes in early adulthood between the ages of 20 and 50 and affects women twice as frequently as men.