Reblozyl
Sponsor
ARTGs
334510 and 334511
334510 and 334511
Device/Product name
Reblozyl
Active Ingredient
Luspatercept
Date of decision
Published
Submission type
New chemical entity
ATC codes
B03XA06
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 Reblozyl 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 | 2 June 2020 |
| First round evaluation completed | 2 November 2020 |
| Sponsor provides responses on questions raised in first round evaluation | 4 January 2021 |
| Second round evaluation completed | 17 March 2021 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 17 August 2021 |
| Sponsor's pre-Advisory Committee response | Not applicable |
| Advisory Committee meeting | Not applicable |
| Registration decision (Outcome) | 27 August 2021 |
| Completion of administrative activities and registration on ARTG | 30 August 2021 |
| Number of working days from submission dossier acceptance to registration decision* | 250 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Black triangle scheme
Yes. This product will remain in the scheme for 5 years, starting on the date the product is first supplied in Australia
Dose forms
Powder for injection
Strength
50 mg/mL
Other ingredients
Citric acid monohydrate, sodium citrate dihydrate, polysorbate 80, sucrose, hydrochloric acid and sodium hydroxide
Containers
Vial
Pack sizes
One
Routes of administration
Subcutaneous injection
Dosage
Dosage of Reblozyl is based on multiple factors, including the condition being treated and the haemoglobin level of the patient.
For further information refer to the Product Information.
Pregnancy category
D Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.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
Reblozyl luspatercept was approved for the following therapeutic use:
Reblozyl is indicated for the treatment of adult patients with transfusion-dependent anaemia (requiring 2 or more RBC units over 8 weeks) due to very low, low and intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS).
Reblozyl is indicated for the treatment of adult patients with transfusion-dependent anaemia associated with beta thalassaemia.
Limitation of Use
Reblozyl is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anaemia.
What is this medicine and how does it work
Luspatercept is a recombinant fusion protein consisting of a modified form of the extracellular domain of the human activin receptor type IIB (ActRIIB) linked to the human immunoglobin G1 (IgG1) fragment constant (Fc) domain. It acts as a ligand trap for select transforming growth factor beta (TGF-β) superfamily ligands. By binding to certain endogenous ligands that act as negative regulators of erythropoiesis, luspatercept inhibits downstream Smad2/3 signalling, resulting in erythroid maturation through differentiation of late-stage erythroid precursors (normoblasts) in the bone marrow. TGF-β superfamily signalling through Smad2/3 is abnormally high in disease models characterised by ineffective erythropoiesis, that is myelodysplastic syndromes (MDS) and β-thalassaemia, and in the bone marrow of MDS patients.
What post-market commitments will the sponsor undertake
- Reblozyl (luspatercept) is to be included in the Black Triangle Scheme. The Product Information and Consumer Medicines Information for Reblozyl must include the black triangle symbol and mandatory accompanying text for 5 years, which starts from the date that the sponsor notifies the TGA of supply of the product.
- The Reblozyl European Union-Risk Management Plan (RMP) (version 1.0, dated 12 May 2020, data lock point May 2018), with Australian Specific Annex (version 2.0, dated 14 December 2020), included with submission PM-2020-01706-1-6, 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 3 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. - Laboratory testing & compliance with Certified Product Details
i. All batches of 334510 Reblozyl (luspatercept) 25 mg powder for injection vial and 334511 Reblozyl (luspatercept) 75 mg powder for injection vial 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 Results http://www.tga.gov.au/ws-labs-index and periodically in testing reports on the TGA website.
Certified Product Details
The Certified Product Details, as described in Guidance 7: Certified Product Details of the Australian Regulatory Guidelines for Prescription Medicines (ARGPM) (http://www.tga.gov.au/industry/pm-argpm-guidance-7...), 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.