Tysabri - A concentrate that is made up into a solution for infusion. It contains
the active substance natalizumab a humanised monoclonal antibody which inhibits the
migration of white cells into the central nervous system, thus reducing inflammation.
It is licensed for the treatment of very active relapsing-remitting multiple sclerosis.
It is used when the disease has failed to respond to a interferon treatment or if
the disease is severe and rapidly becoming worse.
Tysabri works by reducing the number of white blood cells which can leave the blood
and enter the nervous system, therefore reducing the damage to the nervous system.
This mechanism of action is different to that used by treatments that have been used
in treating MS (interferon-beta and glatiramer acetate.)
The active substance natalizumab, is a monoclonal antibody. A monoclonal antibody
is an antibody (a type of protein) that has been designed to recognise and attach
to a specific structure (called an antigen) that is found on certain cells in the
body. Natalizumab has been designed to attach to a specific part of an ‘integrin’
called ‘α4β1 integrin’. This is found on the surface of most leucocytes (white cells
in the blood that are involved in the inflammation process). When blocking the integrin,
natalizumab prevents the leucocytes from going from the blood into the brain reducing
inflammation, and consequently lessening nerve damage caused by Multiple Sclerosis.
Some people being treated with Tysabri may develop neutralising antibodies. This
is because Tysabri is a foreign protein and the body’s immune system naturally produces
antibodies against foreign proteins. Some people may continue to produce neutralising
antibodies known as “persistent antibodies”. When this occurs the effectiveness of
Tysabri will be reduced.
In trials 6% of people developed “persistent antibodies” and therefore stopped treatment
with Tysabri.
The medication is administered intravenously once every four weeks. Tysabri must
be started and continuously supervised by a health professional who is experienced
in treating diseases of the nervous system. Because the infusion can trigger an allergic
reaction, the sufferer must be monitored during the infusion and for one hour afterwards.
Sufferers who receive Tysabri must be given a special alert card that summarises
the key safety information about the medicine. They must show this card to their
support team, as well as to other health professionals treating them, because they
may notice symptoms of Progressive Multifocal Leukoencephalopathy that the person
is not aware of, such as;
Changes in mood.
Changes in behaviour.
Changes in speech.
The person being treated must also be informed about the risk of Progressive Multifocal
Leukoencephalopathy at the start of treatment, and again after two years of treatment.
Contraindications.
Tysabri should not be given if:
A patient is allergic (hypersensitive) to any of the ingredients of Tysabri.
A patient has a serious problem with their immune system (due to a disease, e.g.
Leukaemia / HIV, or due to a medicine they are taking or have previously taken.)
A patient is taking medicines that cannot be used with Tysabri.
A patient has cancer (unless it is a type of skin cancer called basal cell carcinoma.)
A patient is / are under 18 years of age.
A patient is over 65 years of age.
health professionals need to consider the occurrence of infusion reactions, with
especially delayed reactions occurring more frequently than previously assumed.
Delayed infusion reactions occurred in 4 of 40 relapse-remitting multiple sclerosis
people treated with Tysabri.
Side effects may occur such as:
Dizziness .
Nausea.
Fatigue.
Headaches.
Hypersensitivity (allergic) - If this is the case, Tysabri treatment will be stopped
permanently.
Itchy rash (hives).
Joint pains.
Skin reactions.
Sore throat and runny or blocked nose.
Shivering or fever.
Tiredness.
Urinary tract infection.
Vomiting.
Serious Side effects may occur such as:
The very nature of the drugs mechanism of action has led to the detection of a number
of cases of Progressive Multifocal Leukoencephalopathy (PML is a rare and usually
fatal viral disease that is characterized by progressive damage or inflammation of
the white matter of the brain at multiple locations. It occurs almost exclusively
in those with severe immune deficiency).
This very serious disease of the brain is more likely to occur when taking Tysabri
and so regular MRI scanning needs to be undertaken in all such people. For this reason
the medication is only to be prescribed in major neuroscience centres, by specially
experienced neurologists. currently, PML has only been reported in people taking
Tysabri together with other drugs which affect the immune system or in those whose
immune system is not as strong as it should be.
Tysabri is given as a ‘monotherapy’ which means that a person should not take other
medicines which affect the immune system at the same time as Tysabri, including drugs
such as interferon-beta. In addition Tysabri should not be given to those whose immune
systems have reduced effectiveness e.g. HIV or Leukaemia.
The risk of Progressive Multifocal Leukoencephalopathy with Tysabri is thought to
be about one in 1,000, but use of the biologic has been primarily relegated to the
second or third-line setting, despite its apparent efficacy benefit over the traditional
first-line drugs.
A patient's risk of getting Progressive Multifocal Leukoencephalopathy increases
with the number of monthly infusion they receive, something that the foodstuffs and
Drug administration highlighted in a January safety update.
The agency concluded that the benefits of the medicine continue to outweigh the risks:
The rate is about 1.38:1,000 incidences amongst those on the drug for between two
and three years.
The rate is about 0.32:1,000 incidences amongst those using the drug for one to two
years.
The rate and is almost nonexistent in people using it for less than a year.
The more you take Tysabri, the more likely Progressive Multifocal Leukoencephalopathy
could occur.
The possibility of contracting the often-fatal brain disease, Progressive Multifocal
Leukoencephalopathy increases after two years of having the Tysabri infusions.
Biogen Idec today announced a global Phase 3b study, ASCEND, that is being conducted
to evaluate the effectiveness of Tysabri as a treatment for secondary-progressive
multiple sclerosis (SPMS). According to the National Multiple Sclerosis Society,
approximately half of all people initially diagnosed with relapsing-remitting multiple
sclerosis (RRMS) - the most common form of multiple sclerosis (MS) - will transition
to SPMS within 19 years.
Patients with RRMS typically experience unpredictable relapses; the time between
relapses is characterised by full or partial recovery and a lack of disease progression.
SPMS is characterized by a steady progression of nerve damage, symptoms and disability,
but the exact reasons for the progression are unknown. The potential for greater
disease burden in SPMS typically includes decreased mobility, impaired activities
of daily living, loss of independence and reduced quality of life.
"There are limited treatment options available to people living with SPMS and there
is a high unmet need for effective therapies," said Aaron Miller, M.D., member of
the ASCEND advisory board; Medical Director, Corinne Goldsmith Dickinson Center for
Multiple Sclerosis; and Co-Director of the Multiple Sclerosis Care Center at Maimonides
Medical Center in Brooklyn, New York. "The ASCEND trial is investigating whether
treatment with Tysabri may prevent worsening in walking, hand movement and daily
functioning in these patients."
"One hypothesis behind the development of SPMS is that disease progression is a result
of chronic inflammation in the brain tissue trapped behind the blood-brain-barrier.
This causes destruction of the myelin sheath which protects the coating around nerve
fibres, as well as the progressive loss of nerve cells, which can lead to disability
in MS patients," said Professor Richard Reynolds, Professor of Cellular Neuroscience,
Imperial College, London; and Scientific Director of the UK Multiple Sclerosis Society
Tissue Bank. "Preliminary data suggest that Tysabri may hinder this inflammation
in the brain and reduce SPMS-related disease progression; therefore, further investigation
of this hypothesis is warranted."
The ASCEND study is part of the ongoing commitment of both Biogen Idec and Elan to
find ways to improve the well-being of patients with multiple sclerosis.
About the ASCEND Study
ASCEND (A Study to Characterise the Efficacy of Natalizumab on Disability in SPMS)
is a double-blind, placebo-controlled study with SPMS patients being randomized to
receive either Tysabri 300 mg or placebo intravenously every four weeks for 96 weeks.
A global study, ASCEND is expected to enroll approximately 850 patients in 15 countries.
Study participants will be between the ages of 18 and 58, inclusive, with a diagnosis
of SPMS for at least two years; an Expanded Disability Status Scale (EDSS) score
between 3.0 and 6.5, inclusive; MS Severity Score of 4 or higher; documented, confirmed
evidence of disease progression, independent of clinical relapses during the one-year
prior to enrollment; and naive to Tysabri treatment.
The primary endpoint is to investigate whether treatment with Tysabri slows the accumulation
of disability not related to relapses in subjects with SPMS.
Secondary endpoints are:
The proportion of subjects with consistent improvement in Timed 25-foot Walk (T25FW);
The change in subject-reported ambulatory status as measured by the 12-Item MS Walking
Scale (MSWS-12);
The change in manual ability based on the ABILHAND questionnaire;
The impact of Tysabri on subject-reported quality of life using the Multiple Sclerosis
Impact Scale-29 Physical (MSIS-29 Physical);
The change in whole brain volume between the end of study and week 24 using MRI;
and
The proportion of subjects experiencing progression of disability as measured by
individual physical EDSS system scores.
ASCEND is ongoing and actively enrolling patients.
Source: Biogen Idec and Elan Corporation, plc (26/01/12)
