Idefirix
Device/Product name
Idefirix
Active Ingredient
Imlifidase
Date of decision
Published
Submission type
New biological entity
ATC codes
L04AA41
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 Idefirix 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 |
|---|---|
|
Designation (Orphan) |
9 May 2022 |
| Determination (Provisional) |
9 May 2022 |
| Submission dossier accepted and first round evaluation commenced |
1 August 2022 |
| First round evaluation completed |
22 December 2022 |
| Sponsor provides responses on questions raised in first round evaluation |
28 February 2023 |
| Second round evaluation completed |
14 April 2023 |
| Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice |
2 May 2023 |
| Sponsor’s pre-Advisory Committee response |
16 May 2023 |
| Advisory Committee meeting |
1 and 2 June 2023 |
| Registration decision (Outcome) |
7 July 2023 |
| Completion of administrative activities and registration on ARTG |
10 July 2023 |
| Number of working days from submission dossier acceptance to registration decision* | 189 |
*Statutory timeframe for standard applications is 255 working days
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
Powder for concentrate for solution for infusion
Strength
11 mg
Other ingredients
Polysorbate 80, trometamol, mannitol, disodium edetate
Containers
Vial
Pack sizes
1 and 2 vial
Routes of administration
Intravenous infusion
Dosage
Treatment should be prescribed and supervised by specialist physicians experienced in the management of immunosuppressive therapy and of sensitised renal transplant patients.
Imlifidase is restricted to hospital use only.
The dose is based on patient body weight (kg). The recommended dose is 0.25 mg/kg administered as a single dose preferably within 24 hours before transplantation. One dose is adequate for crossmatch conversion in the majority of patients but, if needed, a second dose can be administered within 24 hours after the first dose.
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.
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.
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
Idefirix (imlifidase) was approved for the following therapeutic use:
The provisionally approved new indication(s) for the medicine(s) are:
Idefirix has provisional approval for the desensitisation treatment of highly sensitised adult kidney transplant candidates prior to kidney transplantation from a donor against whom there is a positive cross-match (see Section 5.1 Pharmacodynamic properties, Clinical trials). The use of Idefirix should be reserved for patients who are otherwise unlikely to receive a kidney transplant.
The decision to approve this medicine has been made based on limited data. More comprehensive evidence is required to be submitted.
What is this medicine and how does it work
Imlifidase is a cysteine protease derived from the immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that cleaves the heavy chains of all human IgG subclasses and IgG-type of B-cell receptor (BCR) but no other immunoglobulins. The cleavage of IgG leads to elimination of Fc-dependent effector functions, including complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC). By cleaving all IgG, imlifidase reduces the level of donor specific antibody (DSA), thus enabling transplantation.
What post-market commitments will the sponsor undertake
- Idefirix (imlifidase) is to be included in the Black Triangle Scheme. The PI [Product Information] and CMI [Consumer Medicines Information] for Idefirix must include the black triangle symbol and mandatory accompanying text for five years, or the product’s entire period of provisional registration, whichever is longer.
- The Idefirix EU [European Union]-risk management plan (RMP) (version 1.0, dated 16 June 2020, data lock point 1 December 2019), with Australia specific annex (version 0.2, dated 21February 2023), included with Submission PM-2022-02499-1-2, 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.
- Confirmatory trial data (as identified in the sponsor’s plan to submit comprehensive clinical data on the safety and efficacy of the medicine before the end of the 6 years that would start on the day that registration would commence) must be provided. Specifically, the sponsor must provide the clinical study reports (CSRs) for studies as specified in the ‘Clinical study plan for provisional registration’ section of the Idefirix EU-risk management plan (RMP) Australia specific annex (version 0.2, dated 21February 2023):
- Study 17-HMedIdeS-14 (Study 14) (expected in fourth quarter of 2023)
- Study 20-HMedIdeS-19 (Study 19) (expected in fourth quarter of 2025)
- Study 20-HMedIdeS-17 (Study 17) (expected in second quarter of 2025)
- Additional and separate to the confirmatory trial data specified above, the sponsor should provide the clinical study reports (CSRs) for the following studies, once available:
- Study 20-HMedIdeS-20 (Study 20) (expected in fourth quarter of 2030)
- Study 21-HMedIdeS-25 (Study 25) (expected in second quarter of 2029)
- An observational study of renal transplant recipients (from deceased or living donors) following desensitisation with imlifidase conducted in Australia.
- Laboratory testing & compliance with Certified Product Details (CPD)
i. All batches of Idefirix (imlifidase) supplied in Australia must comply with the product details and specifications approved during evaluation and detailed in the Certified Product Details (CPD).
ii. 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 Resultshttp://www.tga.gov.au/ws-labs-index and periodically in testing reports on the TGA website.
- Certified Product Details
The Certified Product Details (CPD), as described in Guidance 7: Certified Product Details of the Australian Regulatory Guidelines for Prescription Medicines (ARGPM), in PDF format, for the above products should be provided upon registration of these therapeutic goods. In addition, an updated CPD should be provided when changes to finished product specifications and test methods are approved in a Category 3 application or notified through a self-assessable change.
A template for preparation of CPD for biological prescription medicines can be obtained from the TGA website:
[for the form] https://www.tga.gov.au/form/certified-product-details-cpd-biological-prescription-medicines
[for the CPD guidance] https://www.tga.gov.au/resources/resource/guidance/guidance-7-certified-product-details
- For all injectable products the Product Information must be included with the product as a package insert.
Further Information
- The latest Product Information (PI) and Consumer Medicines Information (CMI) can be found at the Australian Register of Therapeutic Goods (ARTG) search page.
- Australian Public Assessment Reports (AusPARs) can be found at the AusPAR search page.
- The latest news and updates regarding therapeutic goods regulation can be found at the TGA news page.