Tysabri

Tysabri (natalizumab) is a type of protein called a monoclonal antibody that is produced from mammalian cells using recombinant DNA techniques (a series of procedures used to join together DNA segments). Tysabri is the first in a class of agents called selective adhesion molecule inhibitors. In MS, inflammatory T cells enter the central nervous system by attaching to the blood-brain barrier with “sticky molecules”, called alpha-4 integrins. Tysabri blocks alpha-4 integrin and prevents T cells from entering the central nervous system, where they cause inflammation and damage to myelin (the insulating material that protects nerves and helps them work properly).

INDICATIONS AND USE
Health Canada approved Tysabri in 2006 for people with relapsing- remitting MS to reduce the frequency of relapses, delay the progression of disability and reduce the number and volume of brain lesions seen on magnetic resonance imaging (MRI).

Tysabri is indicated as a monotherapy (not combined with other therapies). It is generally recommended for people with MS who have not responded adequately to other disease-modifying therapies or who are unable to tolerate them. This is because of an increased risk of progressive multifocal leukoencephalopathy (PML). PML is a rare brain disease caused by the JC virus that can cause severe disability or death. The condition usually affects people with suppressed immune systems. Three cases of PML were reported in clinical trials of Tysabri. There were two deaths: one in a person with MS who was also taking Avonex, and one in a person with Crohn’s disease who was also taking immunosuppressants.

Since Tysabri was introduced in to the market in 2006, 95 cases of PML and 20 deaths have been reported. New data suggests that the risk of developing PML increases with longer treatment duration however the risk for people taking Tysabri beyond 3 years is yet to be determined. The risk of PML also increases in people who have been treated with an immunosuppressant prior to receiving Tysabri.

The risk of PML in people taking Tysabri has been estimated to be 1 in 1000 (0.1%) during 18 months of treatment.18 A large-scale study (TYGRIS) is currently investigating the risk of PML in people receiving natalizumab monotherapy for several years.There are no known treatments if PML occurs. The drug’s manufacturers recommend that people who take Tysabri should enrol in the Canadian Tysabri Care Program at 1-888-827-2827.

DOSAGE
The recommended dose of Tysabri is 300 mg every 4 weeks.

ADMINISTRATION
Tysabri is administered as an intravenous (into the vein) injection over time (an infusion) in a specialized infusion centre by a health professional.

SIDE EFFECTS
The most common serious side effects of Tysabri therapy are infections and allergic reactions (rash, swelling, difficulty breathing). Three cases of PML, including 2 deaths, have been reported. Treatment may also be associated with infusion-related reactions (headache, dizziness, fatigue, rash). Less common side effects include anemia, cough, muscle cramps and depression.

Treatment with Tysabri (natalizumab) has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML). PML can cause disability or death. Healthcare professionals must monitor people on Tysabri for any new sign or symptom that may be suggestive of PML. Tysabri should be withheld immediately at the first sign or symptom suggestive of PML.

NEUTRALIZING ANTIBODIES
Some people taking Tysabri develop “neutralizing” antibodies (NAb). Persistent NAbs to Tysabri are associated with a lesser treatment effect and an increased risk of hypersensitivity reactions and/or infusion-related reactions (rigors, nausea/vomiting and flushing). Antibody testing should be performed if NAbs are suspected. The occurrence of NAbs may be transient. If they persist, discontinuation of treatment should be considered.

DRUG IDENTIFICATION NUMBER (DIN)
02286386

COST REIMBURSEMENT
Private and group health plans may provide some coverage for people who meet the prescribing criteria. Financial assistance through the Canadian Tysabri Care Program may be available to people who cannot afford the drug. For more information, call 1-888-827-2827.

REIMBURSEMENT CRITERIA
Assistance with treatment costs varies among provinces and private insurance companies. In most cases, to be reimbursed an individual must have active relapsing-remitting MS (at least 1 or 2 MS attacks in the 1 or 2 years prior to starting treatment) and be ambulatory. The exact definition of “ambulatory” varies among the provincial drug programs and private/group insurance plans. For more information on reimbursement, please contact your nearest division office at 1-800-268-7582, or your provincial government program office (telephone numbers are listed under Provincial Drug Programs - Contact Information).

CLINICAL TRIAL RESULTS

Clinical Trials

Note: Numerous clinical trials have been conducted for each of the disease-modifying therapies. The clinical trials included in this summary are those that have led to Health Canada approval for the therapy to be prescribed and sold in Canada, or that have led provincial health ministries to agree to reimburse the cost of that therapy or to make a significant change to the reimbursement criteria.

Clinical Trials in Relapsing-Remitting MS

AFFIRM Study

AFFIRM: Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis

This clinical trial involved 942 people with relapsing-remitting MS who were treated with either Tysabri or placebo (a treatment that has no active medication) for over 3 years. Results of the study showed that Tysabri reduced the risk of sustained progression of disability compared to placebo. Tysabri reduced the annual relapse rate by 68% compared to placebo and also reduced the number of brain lesions on MRI.¹ [Polman et al. N Engl J Med 2006; 354: 899-910]

SENTINEL Study

SENTINEL: Safety and Efficacy of Natalizumab in Combination with Interferon

Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis This study examined whether the combination of Tysabri and Avonex was safe and more effective than Avonex alone in people who were continuing to have relapses while on Avonex monotherapy. A total of 1,171 people taking Avonex for relapsing-remitting MS were treated with Tysabri or a placebo infusion for up to 120 weeks. The study was stopped one month early after two cases of PML had been reported. At 1 and 2 years, the annual relapse rate was reduced about 54% with the Tysabri/Avonex combination compared to Avonex alone. Combination therapy also reduced the probability of disease progression at 2 years, and reduced the number of brain lesions seen on MRI compared to Avonex alone.² [Rudick et al. N Engl J Med 2006; 354: 911-923]

CURRENT CLINICAL TRIALS
A number of clinical trials involving the five disease-modifying therapies are underway. The studies are examining the effectiveness at different doses and the possible benefits of combining therapies. For more information about clinical trials, please visit the MS Society of Canada website by going to www.mssociety.ca and click on Research.

PHARMACEUTICAL COMPANY
Biogen Idec Canada Inc. 3 Robert Speck Parkway Mississauga, Ontario L4Z 2G5

FURTHER INFORMATION
Further information for persons with MS is available through the Canadian Tysabri Care Program at 1-888-827-2827.

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References

1. Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899-910.


2. Rudick RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354: 911-923.
   

The drug information contained in this publication has been obtained from the manufacturers’ product monographs. Consult the package insert for more detailed information about the product’s indications, contraindications, medical use and side effects. If you are taking any of the medications listed above, do not change the dose or stop taking your medication without consulting your physician first.

Avonex_® is a registered trademark of Biogen Idec Canada Inc.
Betaplus_® is a registered trademark of Bayer HealthCare Pharmaceuticals
Betaseron_® is a registered trademark of Bayer HealthCare Pharmaceuticals Copaxone_® is a registered trademark of Teva Neuroscience
Extavia_® is a registered trademark of Novartis Pharmaceuticals Canada Inc.
Gilenya_® is a registered trademark of Novartis Pharmaceuticals Canada Inc.
Gilenya GO Program_® is a registered trademark of Novartis Pharmaceuticals Canada Inc.
MS Alliance_® is a registered trademark Biogen IDEC Canada
Rebif_® is a registered trademark of EMD Serono Canada Inc.
Multiple Support Program_® is a registered trademark of EMD Serono Canada Inc.
Shared Solutions_® is a registered trademark of Teva Neuroscience
Tysabri_® is a registered trademark of Biogen Idec Canada Inc. and Elan Pharmaceuticals
Tysabri Care Program_® is a registered trademark of Biogen Idec Canada Inc. and Elan Pharmaceuticals


© 2010, National Multiple Sclerosis Society

This resource has been adapted by the Multiple Sclerosis Society of Canada with permission of the National Multiple Sclerosis Society (USA).

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