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Nexviazyme
Sponsor
Device/Product name
Nexviazyme
Active Ingredient
Avalglucosidase alfa
Date of decision
Published
Submission type
New biological entity
ATC codes
Not yet assigned
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 Nexviazyme 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.
This application was evaluated as part of the Australia-Canada-Singapore-Switzerland-United Kingdom (ACCESS) Consortium, with work-sharing between TGA, Health Canada and Swissmedic. Each regulator made independent decisions regarding approval (market authorisation) of the new medicine.
| Description | Date |
|---|---|
| Designation (Orphan) | 15 September 2020 |
| Submission dossier accepted and first round evaluation commenced | 30 November 2020 |
| First round evaluation completed | 31 March 2021 |
| Sponsor provides responses on questions raised in first round evaluation | 1 June 2021 |
| Second round evaluation completed | 19 July 2021 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 31 August 2021 |
| Sponsor's pre-Advisory Committee response | 14 September 2021 |
| Advisory Committee meeting | 30 September and 1 October 2021 |
| Registration decision (Outcome) | 15 November 2021 |
| Completion of administrative activities and registration on ARTG | 17 November 2021 |
| Number of working days from submission dossier acceptance to registration decision* | 196 |
*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
Powder for injection
Strength
100 mg/10 mL
Other ingredients
Histidine, histidine hydrochloride monohydrate, glycine, mannitol and polysorbate 80
Containers
Vial
Pack sizes
1, 5, 10 and 25
Routes of administration
Intravenous infusion
Dosage
Nexviazyme treatment should be supervised by a physician experienced in the management of patients with Pompe disease or other inherited metabolic or neuromuscular diseases.
Adult population
The recommended dose of Nexviazyme is 20 mg /kg of body weight administered every other week. Dose escalation to 40 mg/kg every other week may be considered for patients with infantile onset Pompe disease (IOPD) who experience insufficient control or declining response at the lower dose (see Section 5.1 Pharmacodynamic properties, Clinical trials of the Product Information).
Paediatric population
The safety and efficacy of avalglucosidase alfa were assessed in 19 patients with IOPD (1 to 12 years of age) and one paediatric patient with LOPD (16 years of age) in two different clinical studies (see Section 4.8 Adverse effects (undesirable effects) and Section 5.1 Pharmacodynamic properties, Clinical trials of the Product Information). There are no data available in patients younger than one year.
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
Nexviazyme (avalglucosidase alfa) was approved for the following therapeutic use:
Nexviazyme is indicated for long-term enzyme replacement therapy for the treatment of patients one year of age and older with Pompe disease (acid α-glucosidase deficiency).
What is this medicine and how does it work
Pompe disease (also known as glycogen storage disease type II, acid maltase deficiency, and glycogenosis type II) is a rare metabolic muscle disease inherited in an autosomal recessive manner defined by a deficiency of acid α-glucosidase (GAA), which is necessary for the degradation of lysosomal glycogen. GAA cleaves alpha-1,4 and alpha-1,6 linkages in glycogen under the acidic conditions of the lysosome. Pompe disease results in intra-lysosomal accumulation of glycogen in various tissues, particularly cardiac and skeletal muscles, leading to the development of cardiomyopathy, progressive muscle weakness, and impairment of respiratory function.Avalglucosidase alfa is a recombinant human acid α-glucosidase (rhGAA) that provides an exogenous source of GAA. Avalglucosidase alfa is a modification of alglucosidase alfa in which approximately 7 hexamannose structures each containing two terminal mannose-6-phosphate (bis-M6P) moieties are conjugated to oxidised sialic acid residues on alglucosidase alfa. Avalglucosidase alfa has a 15-fold increase in mannose-6-phosphate (M6P) moieties compared with alglucosidase alfa. Increasing the level of bis-M6P on rhGAA provides a mechanism to drive uptake into the diaphragm and other skeletal muscle via the cation-independent M6P receptor, where it can degrade glycogen and ameliorate tissue damage.
What post-market commitments will the sponsor undertake
- Nexviazyme (avalglucosidase afla) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Nexviazyme 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 Nexviazyme European Union (EU)-risk management plan (RMP) (version 1.2, dated 16 June 2021, data lock point (DLP) 19 March 2020), with Australian specific annex (version 1.2, dated 10 August 2021), included with Submission PM-2020-04578-1-3, 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).
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 DLP for that report.
- All batches of Nexviazyme supplied in Australia must comply with the product details and specifications approved during evaluation and detailed in the certified product details (CPD).
- The sponsor should provide to the TGA the final study reports for any ongoing or planned clinical studies, as were detailed in the response to second round clinical questions submitted with sequence 0005, as they become available. These include final reports for ongoing studies (Study LTS13769, Study EFC14028 (the COMET trial) and Study ACT14132 (the MINI-COMET trial)), as well as the planned study in treatment-naïve infants with infantile onset Pompe disease (IOPD) Study EFC14462 (the BABY-COMET trial).
- 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.
- 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.
- The PI applying to these therapeutic goods must meet the TGA's approval at all times. Any proposed changes to the approved text of the PI, including safety related changes, must be submitted to, and be approved by, the TGA prior to distribution.
- For all injectable products the PI must be included with the product as a package insert.