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Tysabri® (natalizumab)

Infusion treatment for relapsing/Remitting MS

Tysabri® (natalizumab) is a promising new treatment for relapsing remitting MS. It is very new in Australia and has been approved for use in a number of other countries around the world. As a new product, it is generating significant interest in the MS community.

This information is designed to answer the main questions being asked about the product in Australia and includes material sourced from the MS Society of Canada and the National MS Society. For information that relates to any specific prescription of the drug, please consult a neurologist.

What is Tysabri®?

Tysabri® is a laboratory-produced monoclonal antibody that is administered by a once a month infusion at an accredited infusion centre. Tysabri® was approved by the Australian Therapeutic Goods Administration in 2006 for use in relapsing-remitting MS. It is a product of Biogen Idec and Elan Pharmaceuticals.

Tysabri® is designed to hamper the movement of potentially damaging immune cells from the bloodstream, across the blood-brain barrier into the brain and spinal cord.

The drug inhibits this movement by attaching to alpha 4-integrin, a protein on the surface of immune T-cells that normally enables them to adhere to and pass through the blood-brain barrier. Because of this mode of action, Tysabri® is called a selective adhesion molecule inhibitor (or "SAM").

Availability of Tysabri® in Australia

Tysabri® is now available on a private script in Australia at an estimated annual cost of approximately $33,000 per year, plus prescribing fees.

Biogen Idec submitted an initial application to the Pharmaceutical Benefits Advisory Committee (PBAC) in 2006, seeking subsidisation of Tysabri® on the Pharmaceutical Benefits Scheme (PBS).

The PBAC, while recognising the clinical benefits of the treatment, rejected this application, citing an unfavourable cost-effectiveness rating, as well as the need for improved data to substantiate the proposed treatment model. In their assessment, they indicated that more data was needed to assess the absolute effectiveness of Tysabri® relative to treatments already available. Biogen Idec has resubmitted recently for the next PBAC meeting in November 2007.

How effective is Tysabri®?

The information about the effectiveness of the treatment comes primarily from 2 clinical trials, as follows:

In the AFFIRM study (a two-year clinical trial) 942 individuals received either Tysabri® or inactive placebo. In this study, the treatment group experienced:

In the SENTINEL study (also a two-year study), 1171 individuals with MS who were on another MS drug, Avonex and had experienced at least one relapse during the previous 12 months were tested. All participants took Avonex, in combination with either Tysabri® or an inactive placebo given by intravenous infusions every four weeks for up to 116 weeks.

After one year, participants who had Tysabri® added to Avonex experienced:

In the Sentinel trial two cases of progressive multifocal leukoencephalopathy (PML), one of which was fatal, were diagnosed in those on combination therapy.

Safety Concerns about Tysabri®

Tysabri® carries a major safety issue because of the fact that three people who had been in clinical trials developed PML, caused by a common virus called the JC virus. Two of them died, including one woman who had initially been diagnosed with MS.

The true risk of getting PML outside of the clinical trials of people taking Tysabri® is not clear. According to a study published in The New England Journal of Medicine (The New England Journal of Medicine 2006; 354:924-33), the risk in the clinical trials population, who had taken an average of 17.9 doses of Tysabri®, is one in one thousand.

Due to the emergence of the link to PML in the clinical trials, specific safety procedures and patient tracking systems for adverse events have been put in place worldwide.

Biogen Idec has established a large observational study to help evaluate the long-term safety of Tysabri® beyond the clinical trials. The tracking of patients will include an MRI scan of the brain to help determine whether the JC virus that causes PML is present and active.

In Australia, the company is currently providing training to all prescribing neurologists, pharmacists, as well as infusion centres. The training must be completed before any party can prescribe, dispense or administer Tysabri®.

The clinical trials where Tysabri® was taken alone showed that some adverse events (AEs) were reported. Those AEs which were significantly more frequent in those on Tysabri® included:

The clinical trials of Tysabri® in MS did not reveal significant differences in serious infections between those on active treatment versus those on inactive placebo. However, the risks of longer-term exposure to Tysabri® are currently unknown.

People are advised NOT take Tysabri® if they have:

Deciding to use Tysabri®

The suitability of Tysabri® as a treatment needs to be established by a neurologist on an individual basis on a clinical rationale, with full consideration of benefits, risk and costs, not purely on external data. It is important to note that since MS is different for each person, there is no single treatment strategy.

The prescribing information states that Tysabri® should not be given to patients whose immune systems are compromised or weakened, such as people who have MS plus leukaemia or lymphoma, or who are taking immune-suppressing drugs including Novantrone, Cytoxan or Imuran, or monthly intravenous steroids.

In Australia Tysabri® is approved as a mono therapy, so is not to be combined with other MS drugs such as Avonex®, Betaferon®, Rebif®, or Copaxone®.

Until Tysabri® is approved on the PBS, cost is going to be a prohibitive factor for most people. Other factors such as the suitability of current treatments are also relevant to be discussed between neurologists and their patients.

People are advised to contact their neurologist for further information about Tysabri®.