Source: Australian Department of Health
Australian prescription medicine decision summary
The Australian Prescription Medicine Decision Summary provides a short overview of the TGA’s evaluation process leading to the registration of a new prescription medicine on the Australian Register of Therapeutic Goods (ARTG).
More in-depth information about the evaluation will be available in the Australian Public Assessment Report (AusPAR) for a particular prescription medicine, which can be found on the AusPAR search page once published.
Summary of submission
|Anatomical Therapeutic Chemical (ATC) code||N02CD03|
|Date of decision||17 September 2019|
|Date of entry onto ARTG||20 September 2019|
|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.|
|Sponsor’s name and address||
Teva Pharma Australia Pty Ltd
37 Epping Road, Macquarie Park, NSW 2113
|Dose form(s)||Solution for injection|
|Strength(s)||225 mg/1.5 mL|
|Other ingredients||Histidine, Histidine hydrochloride monohydrate, Sucrose, Disodium edetate, Polysorbate 80, Water for injections|
|Pack size(s)||1 or 3|
|Route(s) of administration||Subcutaneous|
225 mg once monthly (monthly dosing) or 675 mg every three months (quarterly dosing).
For further information refer to the Product Information.
What was approved?
Ajovy (fremanezumab) was approved for the following therapeutic use:
Ajovy is indicated for the preventive treatment of migraine in adults.
What is this medicine and how does it work?
Fremanezumab is a fully humanised IgG2Δa/kappa monoclonal antibody produced by recombinant DNA technology that is derived from a murine precursor. Fremanezumab potently and selectively binds the calcitonin gene-related peptide (CGRP) ligand and blocks both CGRP isoforms (α-and β-CGRP) from binding to the CGRP receptor preventing the activation of the trigeminal system. While the precise mechanism of action by which fremanezumab prevents migraine attacks is unknown, it is believed that prevention of migraine is obtained by its effect modulating the trigeminal system.
Fremanezumab is highly specific for CGRP and does not bind to closely related family members (for example, amylin, calcitonin, intermedin and adrenomedullin).
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 Ajovy was considered favourable for the therapeutic use approved.
What steps were involved in the decision process?
The following table summarises the key steps and dates for this application.
|Submission dossier accepted and first round evaluation commenced||28 September 2018|
|First round evaluation completed||3 April 2019|
|Sponsor provides responses on questions raised in first round evaluation||5 June 2019|
|Second round evaluation completed||26 June 2019|
|Delegate’s overall benefit-risk assessment and request for Advisory Committee advice||2 July 2019|
|Sponsor’s pre-Advisory Committee response||12 July 2019|
|Advisory Committee meeting||1-2 August 2019|
|Registration decision (Outcome)||17 September 2019|
|Completion of administrative activities and registration on ARTG||[Date on ARTG record]|
|Number of working days from submission dossier acceptance to registration decision*||202|
What post-market commitments will the sponsor undertake?
The following specific conditions of registration apply to this approval:
- Ajovy (Fremanezumab) is to be included in the Black Triangle Scheme. The PI and CMI and any other agreed additional risk minimisation materials for Ajovy 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 Ajovy (Fremanezumab) EU-Risk Management Plan (RMP) (version 1.4, dated 29 January 2019, data lock point 29 January), with Australian Specific Annex (version 1.1, dated 16 April 2018), included with submission PM-2018-03494-1-1, 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 this 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.
- Ajovy is a new biological entity, and as such meets the inclusion criteria for the Black Triangle Scheme. The relevant warning symbol and statements are included in the supplied PI, CMI and Instructions for Use leaflet. All these risk minimisation materials will be included as a package insert in the primary carton.
Patients eligible for self-administration will be trained by their doctor or nurse per the agreed PI. The CMI and “Instructions for Use” guide warns patients of self-administration without training. Together with the pre-filled syringe, the outpatient is to have access to an injection training video.
PI, CMI and IFU must be included as package insert.
- It is a condition of registration that all batches of Ajovy (fremanezumab) 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 each batch of Ajovy (fremanezumab) 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 you are notified in writing of any variation.
- 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.