The following table summarises the key steps and dates for this comparable overseas regulator approach B (COR-B) application.
|Submission dossier accepted and first round evaluation commenced
|3 June 2019
|First round evaluation completed
|30 September 2019
|Sponsor provides responses on questions raised in first round evaluation
|28 November 2019
|Second round evaluation completed
|2 January 2020
|Delegate's overall benefit-risk assessment
|8 April 2020
|Sponsor's pre-Advisory Committee response
|Advisory Committee meeting
|Registration decision (Outcome)
|15 April 2020
|Completion of administrative activities and registration on ARTG
|20 April 2020
|Number of working days from submission dossier acceptance to registration decision*
* The COR-B process has a 175 working day evaluation and decision timeframe.
Powder: Sodium citrate dehydrate, Glycine, Trehalose dehydrate, Mannitol, Polysorbate 80
Solvent: Water for injections
Veyvondi is not bioequivalent to plasma-derived von Willebrand factor, and individual patient dosage must be calculated specifically for Veyvondi.
Treatment of von Willebrand disease (VWD) should be supervised by a physician experienced in the treatment of haemostatic disorders.
Dosage and frequency of administration must be individualised according to clinical judgement and based on the patient's weight, severity and type of bleeding episodes/surgical intervention, as well as both von Willebrand factor ristocetin cofactor (VWF:RCo) and factor VIII coagulant activity (FVIII:C) levels, and also based on monitoring of appropriate clinical and laboratory measures. Dose based on bodyweight may require adjustment in underweight or overweight patients.
Generally, 1 IU/kg Veyvondi raises the plasma VWF:RCo by 0.02 IU/mL (2%).
Haemostasis cannot be ensured until FVIII:C is at least 0.4 IU/mL (≥ 40% of normal activity). Depending on the patient's baseline FVIII:C levels, a single infusion of recombinant von Willebrand factor (rVWF) will, in a majority of patients, lead to an increase above 40% in endogenous FVIII:C activity within 6 hours and will result in sustaining this level up to 72 hours post infusion. The dose and duration of the treatment depend on the clinical status of the patient, the severity and type of bleeding, and both VWF:RCo and FVIII:C levels. If the patient's baseline plasma FVIII:C level is < 40% or is unknown and in all situations where a rapid correction of haemostasis should be achieved, such as treatment of an acute haemorrhage, severe trauma or emergency surgery, it is necessary to administer a recombinant coagulation factor VIII (rFVIII) product with the first infusion of Veyvondi, in order to achieve a haemostatic plasma level of FVIII:C.
However, if an immediate rise in FVIII:C is not necessary, or if the baseline FVIII:C level is sufficient to ensure haemostasis, the physician may decide to omit the co-administration of rFVIII at the first infusion with Veyvondi.
In case of major bleeding events or major surgeries requiring repeated, frequent infusions, monitoring of FVIII:C levels is recommended, to decide if rFVIII is required for subsequent infusions to avoid excessive rise of FVIII:C.
Patients should be monitored for the development of VWF or FVIII neutralising antibodies (inhibitors). If suspected VWF activity (VWF:RCo) plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, an assay should be performed to determine if a VWF or FVIII inhibitor is present. See Product Information Section 4.4 Special Warnings and Precautions for Use, Neutralising antibodies (inhibitors).
For further information refer to the Product Information.
Veyvondi (vonicog alfa) was approved for the following therapeutic use:
Veyvondi is indicated in adults (age 18 and older) with von Willebrand Disease (VWD), when desmopressin (DDAVP) treatment alone is ineffective or not indicated, for the
- treatment of haemorrhage and surgical bleeding
- prevention of surgical bleeding.
Veyvondi should not be used in the treatment of Haemophilia A.
- Veyvondi (vonicog alfa) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Veyvondi 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 Veyvondi European Union-Risk Management Plan (EU-RMP) (version 1.4, date 18 September 2019; data lock point (DLP) 6 March 2018), with Australian specific Annex (version 1.1, dated 10 January 2020), included with submission PM-2019-01555-1-6, 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 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.
- Batch release testing and compliance with Certified Product Details (CPD)
- It is a condition of registration that all batches of Veyvondi-vonicog alfa 650 IU powder for injection with solvent vials and Veyvondi-vonicog alfa 1300 IU powder for injection with solvent vials 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 Veyvondi-vonicog alfa 650 IU powder for injection with solvent vials and Veyvondi-vonicog alfa 1300 IU powder for injection with solvent vials 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 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.