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Zolgensma
ARTGs
Device/Product name
Zolgensma
Active Ingredient
Onasemnogene abeparvovec
Date of decision
Published
Submission type
New biological entity
ATC codes
M09AX09
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 Zolgensma 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 | 13 November 2019 |
| Submission dossier accepted and first round evaluation commenced | 29 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 | 19 October 2020 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 29 October 2020 |
| Sponsor's pre-Advisory Committee response | 11 November 2020 |
| Advisory Committee meeting | 3 and 4 December 2020 4 and 5 February 2021 |
| Registration decision (Outcome) | 24 February 2021 |
| Completion of administrative activities and registration on ARTG | 4 March 2021 |
| Number of working days from submission dossier acceptance to registration decision* | 199 |
*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
Injection for intravenous infusion
Strength
2 x 1013 vector genomes/mL
Other ingredients
Trometamol, magnesium chloride hexahydrate, sodium chloride, poloxamer, hydrochloric acid (for pH adjustment) and water for injections
Containers
Vial (two fill volumes: 5.5 mL or 8.3 mL)
Pack sizes
The dose of Zolgensma and exact number of vials required for each patient is calculated according to the patient's weight (refer to the Product Information for further information). The pack sizes are: Packs consisting of two to nine of the 8.3 mL vials, and A composite pack consisting of various combinations of the 5.5 mL and 8.3 mL vials (refer to the Product Information for further information).Note: the 5.5 mL vial is not supplied on its own.
Routes of administration
Intravenous infusion
Dosage
For single-dose intravenous infusion only.
Treatment with Zolgensma should be supervised by a physician experienced in the management of patients with spinal muscular atrophy (SMA).
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
An immune response to the adeno-associated viral vector serotype 9 (AAV9) capsid will occur after infusion of Zolgensma, thus patients should not be re-dosed with Zolgensma.
Zolgensma is for a single treatment only.
The recommended dose of Zolgensma is 1.1 × 1014 vector genomes per kilogram (vg/kg) of body weight (see Table 1 in the Product Information).
For further information on dosage, refer to the Product Information.
Pregnancy category
B2Drugs 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
Zolgensma (onasemnogene abeparvovec) was approved for the following therapeutic use:
Zolgensma (onasemnogene abeparvovec) is indicated for the treatment of paediatric patients less than 9 months of age with symptomatic or pre-symptomatic spinal muscular atrophy with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene and 1 to 3 copies of the SMN2 gene.
What is this medicine and how does it work
Spinal muscular atrophy (SMA) is caused by a bi-allelic mutation in the survival motor neuron 1 (SMN1) gene, which results in insufficient survival motor neuron (SMN) protein expression. Zolgensma (onasemnogene abeparvovec) is a non-replicating recombinant adeno-associated viral (AAV) vector that utilises the AAV9 capsid to deliver a stable fully functional copy of the transgene encoding the human survival motor gene protein. The SMN1 gene present in onasemnogene abeparvovec is designed to reside as episomal DNA in the nucleus of transduced cells and is expected to be stably expressed for an extended period of time in post-mitotic cells. The AAV9 virus is not known to cause disease in humans. Intravenous administration of Zolgensma that results in cell transduction and expression of the SMN protein has been observed in two human case studies (see Section 5.2 Pharmacokinetic properties in the Product Information).
What post-market commitments will the sponsor undertake
- Zolgensma (onasemnogene abeparvovec) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicine Information (CMI) for Zolgensma 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 Zolgensma European Union (EU)-Risk Management Plan (RMP), (version 0.7, dated 19 March 2020; data lock point 31 December 2019) with Australian Specific Annex (version 1.1, dated 17 August 2020), included with submission PM-2019-05979-1-3, 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.
- Preparation and administration of Zolgensma is restricted to clinical facilities accredited to the National Safety and Quality Health Service (NSQHS) Standards.
- Laboratory testing and compliance with Certified Product Details (CPD)
- All batches of Zolgensma 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 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.
- For all injectable products the Product Information must be included with the product as a package insert.