TYSABRI

What it is

TYSABRI (natalizumab) is a recombinant humanised IgG4 monoclonal antibody that binds to α4-integrin. The medicine is supplied as a concentrated solution for intravenous infusion containing 300 mg natalizumab per 15 mL dose, and as a subcutaneous injection containing 300 mg natalizumab per dose (two injections of 150 mg/1 mL prefilled syringes).

Approved indications

— Relapsing remitting multiple sclerosis to delay the progression of physical disability and to reduce the frequency of relapse.

Dosing overview

The recommended dose of TYSABRI by intravenous infusion is 300 mg every four weeks. The concentrate should be diluted in 100 mL 0.9% Sodium Chloride and infused over approximately one hour. The recommended dose for subcutaneous injection is also 300 mg every 4 weeks. Injections should be administered one after the other without significant delay, with the second injection administered no later than 30 minutes after the first.

Key safety warnings

TYSABRI is associated with an increased risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that may lead to death or severe disability. There are no known interventions that can reliably prevent PML or adequately treat PML if it occurs. Risk factors associated with an increased risk of developing PML include the presence of anti-JCV antibodies, treatment duration especially beyond 2 years in patients who are anti-JCV antibody positive, and immunosuppressant use prior to receiving TYSABRI. Index values equal to or below 0.9 are associated with a PML incidence of less than 1 per 1000 patients; PML risk increases substantially at index values above 1.5. Early diagnosis from clinical and MRI monitoring, and stopping therapy are important factors in management of PML in patients on TYSABRI. PML has been reported following discontinuation of TYSABRI in patients who did not have findings suggestive of PML at the time of discontinuation, and patients and healthcare professionals should continue to be vigilant for any new signs or symptoms suggestive of PML for approximately 6 months following discontinuation.

Contraindications

TYSABRI should not be administered to patients with known hypersensitivity to natalizumab, any of the excipients, or to murine derived proteins. TYSABRI is contraindicated in patients who have or have had progressive multifocal leukoencephalopathy. TYSABRI should not be administered to patients with increased risk for opportunistic infections, including those immunocompromised due to current or recent immunosuppressive therapies or systemic medical conditions resulting in significantly compromised immune system function such as human immunodeficiency virus, organ transplant, or active malignancy. TYSABRI should not be administered in combination with immunomodulatory agents such as beta interferons or glatiramer acetate.

PBS listing

The injection formulation (150 mg in 1 mL single dose pre-filled syringe) is listed on the PBS with streamlined authority required restriction at an ex-manufacturer price of A$937.30. The solution concentrate for intravenous infusion (300 mg in 15 mL) is also listed on the PBS with streamlined authority required restriction at an ex-manufacturer price of A$937.30.

Regulatory history

TYSABRI natalizumab 300 mg/15 mL concentrate for infusion was first registered on the ARTG on 1 November 2006. The subcutaneous injection formulation (150 mg/1 mL pre-filled syringe) was first listed on 7 December 2021. In November 2014, the PBAC recommended a change to the PBS listing to allow use in patients who have failed prior treatment with a disease-modifying therapy. In July 2019, the PBAC recommended removal of age restrictions from the PBS listing to permit use in paediatric patients. In July 2022, the PBAC recommended removal of prescribing instructions. In March 2023, the PBAC recommended the medicine for relapsing-remitting multiple sclerosis.