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ARTGs
378245
Device/Product name
Evusheld
Active Ingredient
Tixagevimab and cilgavimab
Date of decision
Published
Submission type
New biological entity and change in dosage and change to Product Information requiring evaluation of new data
ATC codes
J06BD03
Decision
Approved for provisional registration
What was the decision based on
The decision was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology), clinical (pharmacology, safety and efficacy) and risk management plan information submitted by the sponsor. The benefit-risk profile of Evusheld was considered favourable for the therapeutic use approved.
What steps were involved in the decision process

Data were provided as a rolling submission. Under normal circumstances, TGA's assessment (for both provisional and general registration) begins once all information to support registration is available. As part of the Department of Health's response to the pandemic, the TGA has agreed to accept rolling data for COVID-19 vaccines and treatments, to enable early evaluation of data as it becomes available.

Date of entry onto ARTG
Black triangle scheme
Yes. As a provisionally registered product, this medicine will remain in the Black Triangle Scheme for the duration of its provisional registration
Dose forms
Solution for injection
Strength
100 mg/mL of tixagevimab and 100 mg/mL of cilgavimab
Other ingredients

Histidine, histidine hydrochloride monohydrate, sucrose, polysorbate 80 and water for injection

Containers
Vial
Pack sizes
Each carton of Evusheld contains two vials:
• 150 mg of tixagevimab in 1.5 mL (100 mg/mL)
• 150 mg of cilgavimab in 1.5 mL (100 mg/mL)
Routes of administration
Intramuscular injection
Dosage

Pre-exposure prophylaxis

The recommended dose is 600 mg of Evusheld, administered as two separate 3 mL, sequential injections of:

  • 300 mg of tixagevimab
  • 300 mg of cilgavimab

Repeat doses of 600 mg of Evusheld (300 mg of tixagevimab and 300 mg of cilgavimab) is optional and may be given once every 6 months at the discretion of the treating health care professional. The decision for whom to implement repeat dosing should be based on the available evidence and patient circumstances. Repeat-dosing should only be considered if the treatment benefit outweighs the associated risks.

Treatment

The recommended dose is 600 mg of Evusheld, administered as two separate 3 mL, sequential injections of:

  • 300 mg of tixagevimab
  • 300 mg of cilgavimab

Evusheld should be given as soon as possible after a positive viral test for SARS-CoV-2 and within 7 days after the onset of symptoms of COVID-19 (see Section 5.1 Pharmacodynamic properties).

For further information regarding dosage, refer to the Product Information.

Pregnancy category
B2
Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed.
Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.
The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. This must not be used as the sole basis of decision making in the use of medicines during pregnancy. The TGA does not provide advice on the use of medicines in pregnancy for specific cases. More information is available from obstetric drug information services in your State or Territory.
What was approved

Evusheld (tixagevimab and cilgavimab) was approved for the following therapeutic use:

Treatment

Evusheld has provisional approval for the treatment of adults with COVID-19, who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19. See Section 4.2 Dose and method of administration and Section 5.2 Pharmacokinetic properties.

This decision has been made on the basis of short-term efficacy and safety data. Continued approval depends on the evidence of longer-term efficacy and safety data from ongoing clinical trial.

What is this medicine and how does it work
Tixagevimab and cilgavimab are two recombinant human immunoglobulin G1κ (IgG1κ) monoclonal antibodies, with amino acid substitutions to extend antibody half-life (YTE) and to reduce antibody effector function and potential risk of antibody-dependent enhancement of disease (TM). Tixagevimab and cilgavimab can simultaneously bind to non-overlapping regions of the spike protein receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Tixagevimab, cilgavimab and their combination bind to spike protein with equilibrium dissociation constants of KD = 2.8 pM, 13.0 pM and 13.7 pM, respectively, blocking its interaction with the human angiotensin converting enzyme 2 (ACE2) receptor, resulting in a blockade of virus entry and effectively neutralising the SARS-CoV-2 virus. Tixagevimab, cilgavimab and their combination blocked RBD binding to the human ACE2 receptor with half maximal inhibitory concentration (IC50) values of 0.32 nM (48 ng/mL), 0.53 nM (80 ng/mL) and 0.43 nM (65 ng/mL), respectively.
What post-market commitments will the sponsor undertake
  • The Evusheld [European Union] EU-risk management plan (RMP) (version 2.2, dated 12 July 2022, data lock point 30 June 2022), with Australia specific annex (version 4.1, dated 19 July 2022), included with Submission PM-2022-03097-1-2, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.

An obligatory component of risk management plans is routine pharmacovigilance. Routine pharmacovigilance includes the submission of periodic safety update reports (PSURs).

Unless agreed separately between the supplier who is the recipient of the approval and the TGA, the first report must be submitted to TGA no later than 15 calendar months after the date of the approval letter. The subsequent reports must be submitted no less frequently than annually from the date of the first submitted report until the period covered by such reports is not less than three years from the date of the approval letter, or the entire period of provisional registration, whichever is longer.

The reports are to at least meet the requirements for PSURs as described in the European Medicines Agency’s Guideline on Good Pharmacovigilance Practices (GVP) Module VII-periodic safety update report (revision 1), Part VII.B Structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration. Each report must have been prepared within ninety calendar days of the data lock point for that report.

  • The final study reports for the following study will have to be submitted before a definitive authorisation can be considered: TACKLE
  • All relevant conditions imposed under the original decision dated 24 February 2022 still apply.

[Visit https://www.tga.gov.au/apm-summary/evusheld to see all relevant conditions imposed under the original decision dated 24 February 2022]

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