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Voxzogo
ARTGs
Device/Product name
Voxzogo
Active Ingredient
Vosoritide
Date of decision
Published
Submission type
New biological entity
ATC codes
M05BX07
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 Vosoritide 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 comparable overseas regulator approach A (COR-A) application.
| Description | Date |
|---|---|
| Designation (Orphan or Provisional if applicable) | 16 June 2021 |
| Submission dossier accepted and first round evaluation commenced | 30 November 2021 |
| First round evaluation completed | 22 April 2022 |
| Sponsor provides responses on questions raised in first round evaluation | 23 May 2022 |
| Second round evaluation completed | 10 June 2022 |
| Delegate's overall benefit-risk assessment | 28 June 2022 |
| Sponsor's pre-Advisory Committee response | Not applicable |
| Advisory Committee meeting | Not applicable |
| Registration decision (Outcome) | 29 June 2022 |
| Completion of administrative activities and registration on ARTG | 6 July 2022 |
| Number of working days from submission dossier acceptance to registration decision* | 117 |
*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
0.8 mg/ml (0.4 mg/0.5 mL, 0.56 mg/0.7 mL) and 2 mg/mL (1.2 mg/0.6 mL)
Other ingredients
Citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, mannitol, methionine, polysorbate 80 and water for injections.
Containers
Vial and pre-filled syringe
Pack sizes
10 vials of Voxzogo and 10 pre-filled syringes of diluent
Routes of administration
Subcutaneous injection
Dosage
Treatment with Voxzogo should be initiated and directed by a physician appropriately qualified in the management of growth disorders or skeletal dysplasias. It is important to initiate treatment in children as young as possible.
The volume of Voxzogo to be administered at the recommended dose is based on the patient's weight and the vosoritide concentration. 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
Voxzogo (vosoritide) was approved for the following therapeutic use:
Voxzogo is indicated for the treatment of achondroplasia in patients 2 years of age and older whose epiphyses are not closed. The diagnosis of achondroplasia should be confirmed by appropriate genetic testing.
What is this medicine and how does it work
Vosoritide is a modified type C natriuretic peptide (CNP). In patients with achondroplasia, endochondral bone growth is negatively regulated due to a gain of function mutation in fibroblast growth factor receptor 3 (FGFR3). Binding of vosoritide to natriuretic peptide receptor-B (NPR-B) antagonises FGFR3 downstream signalling by inhibiting the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the mitogen-activated protein kinase (MAPK) pathway at the level of rapidly accelerating fibrosarcoma serine/threonine protein kinase (RAF-1). As a result, vosoritide, like CNP, acts as a positive regulator of endochondral bone growth as it promotes chondrocyte proliferation and differentiation.
In animal models with open growth plates, vosoritide administration resulted in the promotion of chondrocyte proliferation and differentiation that led to a widening of the growth plate and subsequent increase in skeletal growth. In the mouse models of FGFR3-related chondrodysplasia, a partial or complete normalization of the dwarfism phenotype was observed.
In animal models with open growth plates, vosoritide administration resulted in the promotion of chondrocyte proliferation and differentiation that led to a widening of the growth plate and subsequent increase in skeletal growth. In the mouse models of FGFR3-related chondrodysplasia, a partial or complete normalization of the dwarfism phenotype was observed.
What post-market commitments will the sponsor undertake
- Voxzogo (vosoritide) is to be included in the Black Triangle Scheme. The Product Information and Consumer Medicine Information for Voxzogo 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 Voxzogo European Union (EU)-risk management plan (RMP) (version 2.0, dated 21 June 2021, data lock point 20 November 2019), with Australian specific annex (version 0.2, dated 13 April 2022), included with submission PM-2021-04759-1-5, and any subsequent revisions, to be revised to the satisfaction of 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.
- When available, the sponsor should submit the final results of the Study 111-206, to further evaluate and support the efficacy and safety of vosoritide in patients aged 2 to 5 years.
- The sponsor should inform TGA of any status or PI changes (especially in patients aged 2 to 5 years) including for the comparable overseas regulators based on Study 111-206 or from the missing information as listed in the RMP.
- Laboratory testing & compliance with Certified Product Details (CPD)
- All batches of Voxzogo 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 http://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) http://www.tga.gov.au/industry/pm-argpm-guidance-7.htm, 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 Product Information must be included with the product as a package insert.