Fingolimod (FTY720) - Gilenia®
A novel, once-daily, oral treatment. Fingolimod binds to immune cells known as lymphocytes
trapping them in the lymph nodes. This action lowers the number of circulating T
Cells circulating in the blood stream and central nervous system. A reduction in
inflammation is expected which may reduce damage to the myelin in the brain and spinal
cord.
Side effects may occur
- Fatigue.
- Headache.
- Influenza.
- Increases in alanine aminotransferase (liver enzymes).
- Localised skin malignancies.
- Nasopharyngitis (inflammation of the nasal passage).
A novel, once-daily, oral treatment.
In worldwide Phase III clinical development for the treatment of relapsing-remitting
MS, the form of the disease that affects approximately 85% of people diagnosed with
MS.
Fingolimod FTY720 binds to immune cells known as lymphocytes trapping them in the
lymph nodes. This action lowers the number of circulating T Cells circulating in
the blood stream and central nervous system. A reduction in inflammation is expected
which may reduce damage to the myelin in the brain and spinal cord. Shows sustained
benefits for the majority of patients after three years of treatment
Fingolimod continues to demonstrate sustained benefits in patients with multiple
sclerosis after three years of treatment, according to new clinical data presented
today from an ongoing Phase II study extension.
Results showed that 73% of patients
who began the study on Fingolimod (5 mg dose) remained free from relapses after
three years, and 68% of those who began the study on Fingolimod (1.25 mg dose) remained
relapse-free. The figures after two years of treatment were 77% and 75% respectively.
The 36-month data also showed an average annualised relapse rate of 0.20, equivalent
to one relapse in five years, while 89% of patients were free of the active brain
lesions characteristic of MS as measured by magnetic resonance imaging three years
after starting treatment.
Fingolimod has the potential to be the first in a new class
of therapies for MS that act on inflammation by modulating sphingosine-1-phosphate
receptors reducing the number of inflammatory immune cells, called lymphocytes, from
reaching the brain.
The study has been conducted in Canada and 10 European countries.
Results from the six-month placebo-controlled trial showed that Fingolimod reduced
relapse rates by more than 50% compared to placebo. Current first-line therapies
for MS reduced relapse rates by 30-35% on average in two-year studies. Among patients
originally on placebo who converted to active therapy in the extension, 51% were
free of relapses at three years. The figure at two years was 57%. Fingolimod has
been generally well tolerated throughout the three years of the Phase II study and
its extension.
Oral Drug Reduces Relapse Rates in Multiple Sclerosis
TORONTO—Annualized relapse rates in patients with relapsing-remitting multiple sclerosis
(MS) were more than 50% lower in subjects taking oral fingolimod (FTY720) than in
those taking a placebo, according to research presented at the 62nd Annual Meeting
of the American Academy of Neurology. The medication also reduced the risk of disability
progression by 30% and significantly decreased the number of new or enlarged T2 lesions
and gadolinium-enhancing lesions, per 24-month results of the phase III FTY720 Research
Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial.
Oral fingolimod, a sphingosine 1-phosphate receptor (S1PR) modulator, is the first
in a novel class of drugs under evaluation for the treatment of relapsing and progressive
forms of MS. S1PR modulators work to retain circulating lymphocytes in the lymph
nodes, thereby reducing the recirculation of autoreactive lymphocytes and preventing
penetration of these lymphocytes into the CNS.
Fingolimod Versus Placebo
The double-blind, placebo-controlled multicenter FREEDOMS study randomized 1,083
patients (mean age, 40.5) to receive once-daily doses of either 1.25-mg fingolimod,
0.5-mg fingolimod, or a placebo. For the primary end point of annualized relapse
rate, both doses of fingolimod were superior to placebo, with a 54% reduction in
relapses for the lower dose and a 60% reduction in the higher dose. For the key secondary
end point of time to three-month confirmed disability progression, measured by a
1-point increase in the Expanded Disability Status Scale (EDSS), a 30% risk reduction
was reported in the 0.5-mg dose, and 32% in the 1.25-mg dose, compared with placebo.
“Overall, 1.25-mg fingolimod did not offer any advantages regarding efficacy, and
it had a slightly higher array of side effects; therefore, 0.5 mg is the dosage that
we will submit an application for [FDA] approval at this time,” announced Ludwig
Kappos, MD, of the Department of Neurology, University Hospital, University of Basel,
Switzerland.
The second phase of the study, which was presented in 2006, showed a “clear cut effect
on inflammatory outcomes on MRI,” Dr. Kappos noted. “Five years of follow-up support
these effects…. Approximately 99.5% of patients remaining in the study do not show
MRI activity and have a low annualized relapse rate at approximately 0.2, [which
is equivalent to] one relapse every five years.”
The phase III, 24-month MRI inflammatory activity results favored fingolimod over
placebo, with 50.5% of the 0.5-mg fingolimod group and 51.9% of the 1.25-mg group
free from new or newly enlarged T2 lesions, compared with 21.2% of the placebo group,
reported Ernst-Wilhelm Radue, MD, Director of Medical Image Analysis Center, University
Hospital Basel, Switzerland. In addition, more patients were free from gadolinium-enhanced
lesions with fingolimod (89.7% and 89.8%), compared with placebo (65.1%).
Fingolimod Versus Interferon
A second study, the Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting
Multiple Sclerosis (TRANSFORMS), compared both doses of fingolimod to intramuscular
interferon beta-1a and found that the oral medicine reduced annualized relapse rates
by up to 50%, compared with injectable interferon.
The 12-month phase III study of 1,153 patients also found that fewer patients experienced
relapses requiring steroid treatment and/or hospitalization when treated with fingolimod
than when treated with interferon beta-1a. Patients in both fingolimod groups also
had significantly less deterioration of the ability to perform daily activities,
based on the Patient-Reported Indices for Multiple Sclerosis (PRIMUS)–Activities
scores, compared with the interferon group.
A 24-month optional extension study to assess the safety and efficacy—both clinically
and on MRI—is under way and involves 89% of the patients who completed the core TRANSFORMS
study. Patients who were taking weekly interferon beta-1a injections have been switched
to daily oral fingolimod, and those who took fingolimod in the earlier phase of the
trial have continued on the medication. Following the results of the FREEDOMS II
trial, all subjects in the TRANSFORMS extension study are taking the 0.5-mg dose.
Safety and Tolerability
Of the 1,272 patients initially enrolled in the FREEDOMS trial, 81% completed the
study. Those who discontinued the trial were proportionately lower in the 0.5-mg
fingolimod group (19%), compared with the 1.25-mg dose (31%) or placebo (28%) groups.
The percentages of patients reporting any adverse events were similar for both fingolimod
groups (94%) and placebo (93%). Serious adverse events were reported in 10% of patients
taking 0.5-mg fingolimod, 12% of those taking 1.25-mg fingolimod, and 13% of the
placebo group. Serious infectious adverse events occurred in 1.6% of the 0.5-mg group,
2.6% of the 1.25-mg group, and 1.9% of the placebo group.
Malignant neoplasms were reported in 10 patients in the placebo group and four patients
in each active group. Seven cases of macular edema occurred, all in patients on the
1.25-mg dose. A transient heart rate decrease at the beginning of treatment, minor
increases in blood pressure, and increases in liver enzymes were also observed.
“These results confirm that fingolimod is generally well tolerated,” the researchers
reported. “The 0.5-mg dose was generally better tolerated than the 1.25-mg dose,
[and was] associated with fewer bradycardia and serious adverse events and no cases
of macular edema.”
Source - Neurology Reviews - website
- Lymphocytes - A type of white blood cell that does not contain haemoglobin. White
blood cells are made by bone bone marrow and help the body fight infection and other
diseases, as part of the immune system.
Lymphocytes have a number of roles in the
immune system, including the production of antibodies and other substances that fight
infection and diseases. - Lymphatic System - The tissues and organs that produce, store, and carry white blood
cells that fight infection and other diseases. The lymphatic system includes the
bone marrow, spleen, thymus and lymph glands and a network of thin tubes that carry
lymph and white blood cells into all the tissues of the body. Lymph nodes are like
filters removing unwanted matter from lymph fluid.
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