Equipping People To Make Sense Of What They Are Told
Fingolimod - Gilenya acts on certain types of white blood cells (lymphocytes) which
are involved in this immune attack. It attaches to special locations (or receptors)
on the surface of lymphocytes, called sphingosine-1-phosphate receptors (S1P-R).
This causes a large proportion of the lymphocytes to be retained in lymph nodes which
are part of the body's immune system.
This reduces the number of lymphocytes circulating in the blood, therefore number
of lymphocytes reaching the central nervous system is less, resulting in reduced
immune attack on nerve cells in the brain and spinal cord.
There is considered thought that fingolimod may have a direct effect on nerve cell
damage and enhance remyelination by acting on sphingosine receptors in the central
nervous system.
Gilenya was developed as a new way to prevent rejection in kidney transplant people.
However, at the necessary dosage, the drug was far too toxic. The dose that would
be used to treat MS is five times lower than the lowest dose tested in the transplant
studies.
Even at this dosage, Gilenya can have severe toxicity.
March 2011 - The drug has been approved for use in Canada. Novartis submitted clinical
trial data to Health Canada to get the approval. As of March 9, 2011, Gilenya is
authorized for sale in Canada," Novartis expects the drug will be priced "competitively"
to similar MS medications at about $30,000 per year. Source - CBC
Side effects may occur such as:
Fatigue.
Headache.
Influenza.
Nasopharyngitis (inflammation of the nasal passage).
Serious Side effects may occur such as:
Decrease in heart rate - Bradycardia
Greater risk of infection - Fewer white blood cells means less protection against
infections.
Macular edema of the eye - swelling of the central portion of the retina, causing
distorted vision.
Increases in alanine aminotransferase - liver enzymes.
Localised skin malignancies.
Women who are pregnant should not take Gilenya - it can harm the foetus. It is not
known if Gilenya is passed through breast milk, therefore nursing mothers are warned
not to take the drug.
Two fatal herpes infections occurred in MS people treated with Gilenya at 2.5 times
the 0.5-milligram dose for which Novartis is seeking approval.
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.
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.
Brinkmann V, et al. FTY720: sphingosine 1-phosphate receptor-1 in the control of
lymphocyte egress and endothelial barrier function.American Journal of Transplantation
2004; 4: 1019-25
Miron VE, et al. Cyclical and dose-dependent responses of adult human mature oligodendrocytes
to fingolimod. American Journal of Patholology 2008; 173: 1143-1152
Miron VE, et al. Fingolimod (FTY720) enhances remyelination following demyelination
of organotypic cerebellar slices. American Journal Pathology 2010;176:2682-2694
Kappos L, et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. New England
Journal of Medicine 2006;355(11):1124-1140 -PubMed
European Medicines Agency to review Gilenya
The European Medicines Agency has begun a formal review of the benefits and risks
of fingolimod following reports of serious heart problems after the first dose
Fingolimod is a new, oral disease modifying drug licensed in the UK for people with
relapsing remitting MS who have not responded to one of the beta interferon drugs
or glatiramer acetate or whose multiple sclerosis is getting worse very quickly (experiencing
two or more relapses a year). The treatment requires carefully monitoring for the
first six hours after starting the therapy as experience in clinical trials had shown
that fingolimod can temporarily slow the heart rate.
The European Medicines Agency review was started after reports of people experiencing
heart problems, and the death of a 59 year old person in the US within 24 hours of
receiving their first dose of fingolimod. Since the drug has been licensed, six cases
of unexplained death have also been reported after starting treatment with the drug,
three of which were sudden. In addition, there have been other serious reports including
three deaths due to heart attack and one due to disruption of the heart rhythm.
It is unknown whether these deaths are related to treatment. The review is expected
to be finalised by March 2012.
Whilst the review is ongoing, the doctors giving the drug have been advised to increase
cardiac monitoring of people.
In August 2011, NICE issued a draft recommendation that fingolimod was not a cost
effective treatment for the NHS to provide in England and Wales. Following a period
of consultation, this recommendation was confirmed in December 2011. NICE expects
to publish its final guidance to the NHS in April 2012.
The European Medicines Agency advised doctors to continuously monitor patients for
six hours after giving them a first dose of Novartis AG's multiple sclerosis drug
Gilenya, casting a shadow over the potential blockbuster product.
The move came as the organisation started a review into the safety of the medicine,
following reports of heart problems in patients and the death of one person in the
United States within 24 hours of starting treatment.
The Swiss drugmaker said last month it was investigating whether Gilenya, seen by
analysts as a potential multibillion-dollar seller, caused the death of the 59-year-old
U.S. patient.
Gilenya can temporarily slow the heart rate. Although this usually returns to normal
after a few hours, the European watchdog recommended intense cardiovascular monitoring
after the first dose. This should include electrocardiogram (ECG) monitoring before
treatment and then continuously for the first six hours afterwards, as well as measurement
of blood pressure and heart rate every hour.
Mark Schoenebaum, an analyst at ISI Group, said the call for active ECG monitoring
was very different from the U.S. Food and Drug Administration (FDA) recommendation
of observation and could encourage European doctors to use Biogen Idec's experimental
BG-12. "We believe active ECG monitoring for six hours could be a material impediment
to starting patients on Gilenya and could enhance BG-12's attractiveness to EU physicians
once approved," he said.
The FDA said on December 20 it was also looking into the U.S. case. Regulators on
both sides of the Atlantic said the exact cause of the patient's death was still
unexplained. Novartis was not immediately available for comment.
"It's a bit early to draw too many conclusions on the basis of just one case, but
if this keeps happening and serious cardiovascular problems turn out to be an issue,
then this will definitely spook doctors," Vontobel analyst Andrew Weiss said.
European authorities approved Gilenya last March for people with highly active relapsing-remitting
multiple sclerosis (RRMS), the commonest form of the debilitating disease. More than
30,000 people have received the drug worldwide.
Novartis is banking on the success of its newest drugs, such as Gilenya, to help
it protect its top and bottom lines as established medicines lose patent protection
and face competition from cheaper copies. Analysts, on average, forecast annual sales
of $1.8 billion by 2016, according to Thomson Reuters Pharma.
Gilenya is likely to face increased competition as other drugmakers such as Biogen
and Sanofi push ahead with their latest MS medicines.
Some experts have tipped Biogen's BG-12 to become the world's leading treatment for
multiple sclerosis, while Sanofi's Genzyme unit plans to submit Lemtrada for approval
in the United States and Europe in the first quarter of 2012.
BG-12's key competitive advantage may lie in its safety profile, which looks relatively
clean based on two-year data, analysts have said.
Multiple sclerosis affects 2.5 million people worldwide and is a chronic, often disabling
disease that attacks the central nervous system and can lead to numbness, paralysis
and loss of vision.
