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The Australian Prescription Medicine Decision Summary provides a short overview of the TGA's evaluation process leading to the registration of a new prescription medicine on the Australian Register of Therapeutic Goods (ARTG).
More in-depth information about the evaluation will be available in the Australian Public Assessment Report (AusPAR) for a particular prescription medicine, which can be found on the AusPAR search page once published.
Australian prescription medicine decision summary
|Submission type|| |
New biological entity
|Product name|| |
|Active ingredients|| |
|ATC codes|| |
Not yet assigned
|Date of decision|| |
29 April 2020
|Date of entry onto ARTG|| |
6 May 2020
|Original publication date|| |
14 May 2020
|ARTG numbers|| |
|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
Sanofi-Aventis Pty Ltd
|Sponsor address|| |
12-24 Talavera Road, Macquarie Park, NSW 2113
|Dose forms|| |
20 mg/mL (500 mg/25 mL or 100 mg/5 mL)
|Other ingredients|| |
Sucrose, Histidine hydrochloride monohydrate, Histidine, Polysorbate 80, Water for injections
|Pack sizes|| |
|Routes of administration|| |
Sarclisa should be administered by a healthcare professional, in an environment where resuscitation facilities are available.
Premedication should be used prior to each Sarclisa infusion with the following medications to reduce the risk and severity of infusion reactions (IRs):
Above recommended dose of dexamethasone (administered orally or intravenously) corresponds to the total dose to be administered only once before the infusion, as part of the premedication and the backbone treatment, before isatuximab and pomalidomide administration.
The recommended premedication agents should be administered 15 to 60 minutes prior to starting a Sarclisa infusion. Patients who do not experience an IR upon their first 4 administrations of Sarclisa may have their need for subsequent premedication reconsidered.
The recommended dose of Sarclisa is 10 mg/kg body weight administered as an intravenous infusion (IV) in combination with pomalidomide and dexamethasone, according to the schedule below:
Each treatment cycle consists of a 28 day period. Treatment is repeated until disease progression or unacceptable toxicity.
For other medicinal products that are administered with Sarclisa, refer to the respective current Product Information.
The administration schedule must be carefully followed. If a planned dose of Sarclisa is missed, administer the dose as soon as possible and adjust the treatment schedule accordingly, maintaining the treatment interval.
For further information refer to the Product Information.
|Pregnancy category|| |
Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. 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.
Sarclisa (isatuximab) was approved for the following therapeutic use:
Sarclisa is indicated in combination with pomalidomide and dexamethasone, for the treatment of patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor (PI).
Isatuximab is an immunoglobulin G1 (IgG1)-derived monoclonal antibody that binds to a specific extracellular epitope of cluster of differentiation 38 (CD38) receptor and triggers several mechanisms leading to the death of CD38 expressing tumuor cells.
CD38 is a transmembrane glycoprotein with ectoenzymatic activity, expressed in haematological malignancies, and is highly and uniformly expressed on multiple myeloma cells.
Isatuximab acts through immunoglobulin G fragment crystallisable (IgG Fc)-dependent mechanisms including: antibody dependent cell mediated cytotoxicity (ADCC), antibody dependent cellular phagocytosis (ADCP), and complement dependent cytotoxicity (CDC). Isatuximab can also trigger tumuor cell death by induction of apoptosis via an Fc-independent mechanism.
In human peripheral blood mononuclear cells (PBMCs), natural killer (NK) cells express the highest CD38 levels. In vitro, isatuximab can activate NK cells in the absence of CD38 positive target tumour cells through a mechanism which is dependent of the Fc portion of isatuximab. Also, isatuximab inhibits regulatory T cells (Tregs) which express higher levels of CD38 in multiple myeloma patients compared to healthy individuals.
Isatuximab blocks the enzymatic activity of CD38 which catalyses the synthesis and hydrolysis of cyclic ADP-ribose (cADPR), a calcium mobilising agent, and this may contribute to immunoregulatory functions. Isatuximab inhibits the cADPR production from extracellular nicotinamide adenine dinucleotide (NAD) in multiple myeloma cells.
The combination of isatuximab and pomalidomide in vitro enhances cell lysis of CD38 expressing multiple myeloma cells by effector cells (ADCC), and by direct tumour cell killing compared to that of isatuximab alone. In vivo experiments using a human multiple myeloma xenograft model demonstrated that the combination of isatuximab and pomalidomide results in enhanced antitumour activity compared to the activity of isatuximab or pomalidomide alone.
The following table summarises the key steps and dates for this application.
This application was evaluated as part of the Australia-Canada-Singapore-Switzerland (ACSS) Consortium, with work-sharing between TGA and Health Canada. Each regulator made independent decisions regarding approval (market authorisation) of the new medicine.
|Designation (Orphan)||14 May 2019|
|Submission dossier accepted and first round evaluation commenced||30 July 2019|
|First round evaluation completed||20 November 2019|
|Sponsor provides responses on questions raised in first round evaluation||23 December 2019|
|Second round evaluation completed||28 February 2020|
|Delegate's overall benefit-risk assessment and request for Advisory Committee advice||24 February 2020|
|Sponsor's pre-Advisory Committee response||16 March 2020|
|Advisory Committee meeting||2 and 3 April 2020|
|Registration decision (Outcome)||29 April 2020|
|Completion of administrative activities and registration on ARTG||6 May 2020|
|Number of working days from submission dossier acceptance to registration decision*||166|
*Statutory timeframe for standard applications is 255 working days
- Sarclisa (isatuximab) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Sarclisa 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 isatuximab (Sarclisa) European Union-Risk Management Plan (EU-RMP) (version 0.1, dated 12 April 2019, data lock point 15 November 2018), with Australian specific Annex (version 1.0, dated 30 June 2019), included with submission PM-2019-02568-1-6, 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).
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. The annual submission may be made up of two PSURs each covering six months. If the sponsor wishes, the six monthly reports may be submitted separately as they become available.
If the product is approved in the EU during the three years period, reports can be provided in line with the published list of EU reference dates 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.
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.
- It is a condition of registration that all batches of:
- Sarclisa isatuximab 500 mg/25 mL concentrated injection vial
- Sarclisa isatuximab 100 mg/5 mL concentrated injection vial imported into/manufactured in Australia must comply with the product details and specifications approved during evaluation and detailed in the Certified Product Details (CPD).
- It is a condition of registration that up to 5 initial batches of:
- Sarclisa isatuximab 500 mg/25 mL concentrated injection vial
- Sarclisa isatuximab 100 mg/5 mL concentrated injection vial
imported into/manufactured in Australia is not released for sale until samples and/or the manufacturer’s release data have been assessed and endorsed for release by the TGA Laboratories Branch. Outcomes of laboratory testing are published biannually in the TGA Database of Laboratory Testing Results.
- The sponsor should be prepared to provide product samples, reference materials and documentary evidence as defined by the TGA Laboratories branch. The sponsor must contact Biochemistry.Testing@health.gov.au for specific material requirements related to the batch release testing/assessment of the product. More information on TGA testing of biological medicines is available at Testing of biological medicines.
This batch release condition will be reviewed and may be modified on the basis of actual batch quality and consistency. This condition remains in place until the sponsor is notified in writing of any variation.
- 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.