The following table summarises the key steps and dates for this application.
|Determination (provisional)||4 November 2021 |
4 January 2022
|Submission dossier accepted and first round evaluation commenced||2 December 2021|
|Evaluation completed||24 February 2022|
|Delegate's Overall benefit-risk assessment and request for Advisory Committee advice||28 January 2022|
|Sponsor's pre-Advisory Committee response||2 February 2022|
|Advisory Committee meeting||3 and 4 February 2022|
|Registration decision (Outcome)||24 February 2022|
|Completion of administrative activities and registration on ARTG||26 February 2022|
|Number of working days from submission dossier acceptance to registration decision*||54|
*Statutory timeframe for standard applications is 255 working days
The recommended dosage is 300 mg of Evusheld administered as two separate 1.5 mL, sequential injections of 150 mg of tixagevimab and then 150 mg of cilgavimab.
In clinical trials, Evusheld was not administered to subjects who have already received a coronavirus disease 2019 (COVID 19) vaccine (see Section 5.1 Clinical trials of the Product Information). The potential effect of Evusheld on the body's immune response to a COVID 19 vaccine is unknown.
For further information refer to the Product Information.
Evusheld (tixagevimab/cilgavimab) was approved for the following therapeutic use:
Evusheld (tixagevimab and cilgavimab) has provisional approval for the pre-exposure prophylaxis of COVID-19 in adults and adolescents aged 12 years and older weighing at least 40 kg,
- who have moderate to severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments that make it likely that they will not mount an adequate immune response to COVID-19 vaccination or
- for whom vaccination with any approved COVID-19 vaccine is not recommended due to a history of severe adverse reaction (for example., severe allergic reaction) to a COVID 19 vaccine(s) and/or COVID‐19 vaccine component(s).
See Section 4.2 Dose and method of administration and Section 5.2 Pharmacokinetic properties.
Evusheld is not recommended as a substitute for vaccination in individuals for whom COVID 19 vaccination is recommended.
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 trials.
- Evusheld (tixagevimab/cilgavimab) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Evusheld must include the black triangle symbol and mandatory accompanying text for the products entire period of provisional registration.
Risk management plan conditions
- The Evusheld core risk management plan (RMP) (version 1, date 2 February 2022; data lock point (DLP) 21 August 2021), with Australian specific annex (version 1.0 succession 3; 15 February 2022), included with Submission PM 2021 05375 1 2, to be revised to the satisfaction of 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.
Additional to the submission of PSURs, expedited monthly summary safety reports (including safety data for patients in Australia and reporting of Australia specific safety concerns) are to be provided for the first 6 months post registration, and thereafter at intervals specified by the TGA.
- The manufacturer is to update the specification acceptance criteria after the manufacture of a total of 20 drug substance (DS)/drug product (DP) batches across both manufacturing sites through submission of a Category 3 application.
- The sponsor is to provide the following data for DS manufacture or as otherwise indicated through submission of a Category 3 application:
- Column chromatography resin lifetime studies with qualification data for small scale models
- Membrane reuse studies
- Hold study validation (cilgavimab)
- Additional drug substance stability data
- The sponsor is to provide the following data to support DP shelf life of 12 months:
- Up to 12 months of acceptable stability data for DP (cilgavimab and tixagevimab) from commercial batches.
- Up to 15 months stability data from two clinical batches manufactured from Process 2 from each DP (tixagevimab and cilgavimab).
- a commitment to complete all ongoing stability studies and report any confirmed out of specification result and proposed remediation approaches to the TGA immediately.
- Laboratory testing and compliance with Certified Product Details (CPD).
- All batches of Evusheld supplied in Australia must comply with the product details and specifications approved during evaluation and detailed in the CPD.
- When requested by the TGA, the sponsor should be prepared to provide product samples, specified reference materials and documentary evidence to enable the TGA to conduct laboratory testing on the product. Outcomes of laboratory testing are published biannually in the TGA database of laboratory testing results and periodically in testing reports on the TGA website.
- The final study reports for the following studies will have to be submitted before a definitive authorisation can be considered: the PROVENT, STORM, CHASER, and TACKLE trials.
- All anti-drug antibody (ADA) assessments that have not been completed at the time of the authorization for subjects from the PROVENT clinical trial for Days 1, 29, 58, and 183.
- Interim analysis results through Day 28 for the first 50 subjects to receive a second dose from the PROVENT repeat-dose sub-study.
- Baseline and all subsequent study visits, of the following biomarkers from the PROVENT repeat-dose sub study: d dimer, P selectin, thrombin, and Factor VIII.
- Top line data, to include safety, pharmacokinetic, ADA, and biomarker results for thrombotic events from the first 9 months of the PROVENT repeat dose sub study.
- Monthly aggregate reports for serious adverse events in the cardiac disorder System Organ Class (SOC) and other non cardiac thrombotic serious adverse events.
- Systematic data collection from spontaneous reporting of cardiac events should be conducted and reported regularly to the TGA.
- The complete 6 month safety summary for the PROVENT, STORM CHASER and TACKLE trials should be submitted for review and should include a critical review of cardiac events and non cardiac vascular events.