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Adakveo
Device/Product name
Adakveo
Active Ingredient
Crizanlizumab
Date of decision
Published
Submission type
New biological entity
ATC codes
B06AX01
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 Adakveo 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 | 22 October 2019 |
| Submission dossier accepted and first round evaluation commenced | 31 January 2020 |
| First round evaluation completed | 30 June 2020 |
| Sponsor provides responses on questions raised in first round evaluation | 31 August 2020 |
| Second round evaluation completed | 13 October 2020 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 2 November 2020 |
| Sponsor's pre-Advisory Committee response | 11 November 2020 |
| Advisory Committee meeting | 3 and 4 December 2020 |
| Registration decision (Outcome) | 6 April 2021 |
| Completion of administrative activities and registration on ARTG | 8 April 2021 |
| Number of working days from submission dossier acceptance to registration decision* | 215 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Original publication date
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
Concentrate for solution for infusion
Strength
10 mg/mL
Other ingredients
Sucrose, sodium citrate, citric acid, polysorbate 80, water for injection
Containers
Vial
Pack sizes
One
Routes of administration
Intravenous infusion
Dosage
Patients aged 16 years and over
The recommended dose of Adakveo is 5 mg/kg administered over a period of 30 minutes by intravenous infusion at Week 0, Week 2, and every 4 weeks thereafter.
Adakveo can be given alone or with hydroxycarbamide (hydroxyurea) (see section 5.1 Pharmacodynamic Properties, Clinical Trials in the Product Information).
For further information refer to the Product Information.
Pregnancy category
B1Drugs 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 have not shown 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
Adakveo (crizanlizumab) was approved for the following therapeutic use:
Adakveo is indicated for the prevention of recurrent vaso-occlusive crises in patients aged 16 years and older with sickle cell disease.
What is this medicine and how does it work
Crizanlizumab is a selective immunoglobulin G2 (IgG2) kappa humanised monoclonal antibody (mAb) that binds to P-selectin with high affinity and blocks the interaction with its ligands including P-selectin glycoprotein ligand 1 (PSGL-1). Crizanlizumab can also dissociate preformed P-selectin/PSGL-1 complex. P-selectin is an adhesion molecule expressed on activated endothelial cells and platelets. It plays an essential role in the initial recruitment of leukocytes and the aggregation of platelets to the site of vascular injury during inflammation.In the chronic pro-inflammatory state associated with sickle cell disease, P-selectin is over-expressed and circulating blood cells and the endothelium are activated and become hyperadhesive. P-selectin mediated multi-cellular adhesion is a key factor in the pathogenesis of vaso-occlusion and vasoocclusive crises. Elevated levels of P-selectin are found in patients with sickle cell disease.Binding P-selectin on the surface of the activated endothelium and platelets has been shown to effectively block interactions between endothelial cells, platelets, red blood cells, and leukocytes, thereby preventing vaso-occlusion.
What post-market commitments will the sponsor undertake
- Adakveo (crizanlizumab) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Adakveo 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 Adakveo European Union (EU)-Risk Management Plan (RMP) (version 1.3, date 3 August 2020, data lock point (DLP) 19 October 2018, SEG101A2202 4 October 2019), with Australian Specific Annex (version 1.2, dated 20 October 2020), included with PM-2019-05705-1-6, 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.
- Batch release testing and compliance with Certified Product Details
All batches of Adakveo supplied in Australia must comply with the product details and specifications approved during evaluation and detailed in the Certified Product Details (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.
- Certified Product Details
The 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.
- For all injectable products the PI must be included with the product as a package insert.