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Arexvy
Australian Prescription Medicine Decision Summary
Device/Product name
Arexvy
Active Ingredient
Recombinant respiratory syncytial virus pre-fusion F protein
Date of decision
Published
Submission type
New Biological Entity
Decision
Approved
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 Arexvy was considered favourable for the therapeutic use approved.
What steps were involved in the decision process
Registration timeline
The following table summarises the key steps and dates for this application.
Description | Date |
|---|---|
Submission dossier accepted and first round evaluation commenced
| 31 January 2023
|
Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice | 31 October 2023
|
Advisory Committee meeting | 29 November 2023
|
Registration decision (Outcome) | 8 January 2024
|
Completion of administrative activities and registration on ARTG | 14 January 2024
|
Number of working days from submission dossier acceptance to registration decision* | 166
|
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Black triangle scheme
Yes
Dose forms
Powder for injection
Strength
120 micrograms/0.5 mL
Containers
Vial
Pack sizes
One and 10
Routes of administration
Intramuscular
Dosage
Arexvy is administered as a single dose of 0.5 mL. The need for revaccination has not been established.
For further information 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.
The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. The pregnancy database 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.
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.
The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. The pregnancy database 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
Arexvy (recombinant respiratory syncytial virus pre-fusion F protein) was approved for the following therapeutic use:
Arexvy is indicated for active immunisation of individuals 60 years and older for the prevention of lower respiratory tract disease caused by respiratory syncytial virus (RSV).
The use of this vaccine should be in accordance with official recommendations.
What is this medicine and how does it work
The RSVPreF3 antigen in Arexvy is derived from the laboratory-adapted RSV-A A2 strain, stabilised in the pre-fusion conformation of the naturally occurring F protein for which both RSV-A and B subtypes share high amino acid sequence homology. The risk of developing RSV-associated lower respiratory tract disease (LRTD) increases with age and with presence of underlying comorbidities. Arexvy induces the functional humoral immune responses against the RSV-A and RSV-B subtypes and the antigen-specific cellular immune responses which contribute to protect against RSV-associated LRTD (see Immunogenicity of Arexvy in the Product Information).
In a Phase I/II clinical trial, formulation adjuvanted with AS01E showed the ability to induce RSVPreF3-specific CD4+ T cells in adults 60 to 80 years of age to levels similar to those observed in young adults, despite lower baseline levels in the older adults.
Nonclinical data show that AS01E induces a local and transient activation of the innate immune system. The adjuvant effect of AS01E is the result of interactions between MPL and QS-21 formulated in liposomes. This facilitates the recruitment and activation of antigen presenting cells carrying vaccine-derived antigens in the draining lymph node, which in turn leads to the generation of RSVPreF3-specific CD4+ T cells and induction of RSV-A and RSV-B neutralising antibody responses. In addition, RSVPreF3 formulated with AS01E can elicit specific binding antibodies directed to site Ø, a highly neutralising sensitive epitope, exposed only on the pre fusion conformation of the F protein.
In a Phase I/II clinical trial, formulation adjuvanted with AS01E showed the ability to induce RSVPreF3-specific CD4+ T cells in adults 60 to 80 years of age to levels similar to those observed in young adults, despite lower baseline levels in the older adults.
Nonclinical data show that AS01E induces a local and transient activation of the innate immune system. The adjuvant effect of AS01E is the result of interactions between MPL and QS-21 formulated in liposomes. This facilitates the recruitment and activation of antigen presenting cells carrying vaccine-derived antigens in the draining lymph node, which in turn leads to the generation of RSVPreF3-specific CD4+ T cells and induction of RSV-A and RSV-B neutralising antibody responses. In addition, RSVPreF3 formulated with AS01E can elicit specific binding antibodies directed to site Ø, a highly neutralising sensitive epitope, exposed only on the pre fusion conformation of the F protein.
What post-market commitments will the sponsor undertake
- Arexvy (recombinant respiratory syncytial virus pre-fusion F protein) is to be included in the Black Triangle Scheme. The PI [Product Information] and CMI [Consumer Medicine Information] for Arexvy must include the Black Triangle symbol and mandatory accompanying text for five years, which starts from the date that the sponsor notifies the TGA of supply of the product.
- The Arexvy EU [European Union]-risk management plan (RMP) (version 1.0, dated 3 May 2023, data lock point 30 April 2022), with Australia-specific annex (version 3.0, dated 5 October2023), included with Submission PM-2022-05281-1-2, 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).
Reports are to be provided in line with the current published list of EU reference dates and frequency of submission of PSURs until the period covered by such reports is not less than three years from the date of the approval letter. 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 (Rev 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.
- Quality
GMP clearance for listed manufacturers: All relevant manufacturing sites require approved and current GMP Clearances prior to Australian supply. A commitment is required from the sponsor that they maintain the validity of all manufacturer GMP Clearances for the duration of product supply to Australia. Additionally, that adherence to the conditions of GMP Clearance approval is upheld.
Stability (DS [drug substance] and DP [drug product]): Provide the results from: (DS) ongoing stability studies performed on PPQ lots and commercial lots (process 2.4) at -45°C ± 10°C as part of the annual stability program; (DP) ongoing stability studies performed on PPQ lots and commercial lots (process 2.4) at 2°C to 8°C as part of the annual stability program; and (AS01E Adjuvant System) Commercial lots (Series C lots or PPQ lots) at 2°C to 8°C as part of the annual stability program.
- Batch Release Testing and Compliance
It is a condition of registration that all independent batches of Arexvy Recombinant Respiratory Syncytial Virus pre-fusion F protein vaccine 120 micrograms powder vial and suspension vial for suspension for injection vaccine imported into Australia are not released for sale until samples and the manufacturer’s release data have been assessed and you have received notification acknowledging release from the Laboratories Branch, TGA.
For each independent batch of the product imported into Australia, the sponsor must supply the following:
- A completed Request for Release Form, available from vaccines@health.gov.au.
- Complete summary protocols for manufacture and QC, including all steps in production in the agreed format.
- At least 10 (ten) vials (samples) of each manufacturing batch of Arexvy Recombinant Respiratory Syncytial Virus pre-fusion F protein vaccine 120 micrograms powder vial and suspension vial for suspension for injection vaccine with the Australian approved labels, PI and packaging (unless an exemption to supply these has been granted) representative of all batches of product seeking distribution in Australia.
- If the manufacturing batch has been released in Europe or United Kingdom a copy of the EU Official Control Authority Batch Release (OCABR) certificate (or equivalent from the UK) must be provided.
- Any reagents, reference material and standards required to undertake testing, as requested by Laboratories Branch, TGA.
Sponsors must provide all requested samples and data in sufficient time (at least 5 business days) prior to any distribution date to allow the TGA to perform testing and review. Distribution of each batch of vaccine is conditional upon fulfilment of these conditions and receipt of a letter from the Laboratories Branch acknowledging release.
Samples and data should be forwarded to the Biotherapeutics Section, Laboratories Branch before release of each batch and with sufficient lead time to allow for Laboratories Branch testing. The address for courier delivery is:
ATTN: Batch Release Coordinator
Batch Release Unit
TGA Laboratories Branch
1 Tindal Lane
Canberra Airport ACT 2609
The shipments (including reagents) to TGA are the responsibility of the Australian sponsor/agent who will be required to facilitate the import and customs clearance process.
- Certified Product Details
An electronic copy of the Certified Product Details (CPD) as described in Guidance 7: Certified Product Details of the Australian Regulatory Guidelines for Prescription Medicines (ARGPM) should be provided upon registration of the therapeutic good. In addition, an updated CPD, for the above product incorporating the approved changes is to be provided within one month of the date of approval letter. A template for preparation of CPD for biological prescription medicines and Vaccines can be obtained from the TGA website [for the form] [for the CPD guidance]. The CPD should be sent as a single bookmarked PDF document to Vaccines@health.gov.au as soon as possible after registration/approval of the product or any subsequent changes as indicated above.
More information
The latest Product Information (PI) and Consumer Medicine Information (CMI) can be found by searching the Australian Register of Therapeutic Goods (ARTG).
Australian Public Assessment Reports (AusPARs) can be found by searching our AusPAR dataset.
The latest news and updates regarding therapeutic goods regulation can be found on our news page.