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Alhemo
ARTGs
Device/Product name
Alhemo
Active Ingredient
Concizumab
Date of decision
Published
Submission type
New Biological Entity
ATC codes
Not yet available
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 Alhemo 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 |
|---|---|
|
Submission dossier accepted and first round evaluation commenced |
23 September 2022 |
| First round evaluation completed |
10 January 2023 |
| Sponsor provides responses on questions raised in first round evaluation |
18 November 2022 |
| Second round evaluation completed |
6 April 2023 |
| Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice |
7 March 2023 |
| Sponsor’s pre-Advisory Committee response |
16 March 2023 |
| Advisory Committee meeting |
30 and 31 March 2023 |
| Registration decision (Outcome) |
3 July 2023 |
| Completion of administrative activities and registration on ARTG |
5 July 2023 |
| Number of working days from submission dossier acceptance to registration decision* | 141 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Black triangle scheme
Yes
Dose forms
Solution for injection
Strength
10 mg/mL, 40 mg/mL and 100 mg/mL
Other ingredients
Arginine hydrochloride, histidine, sodium chloride, sucrose, polysorbate 80, phenol, hydrochloric acid, sodium hydroxide, water for injections
Containers
Pre-filled pen
Pack sizes
One
Routes of administration
Subcutaneous
Dosage
Treatment should be initiated under the supervision of a physician experienced in treatment of haemophilia and/or bleeding disorders. Initiate concizumab in a non-bleeding state, and after discontinuing treatment with bypassing agents. Discontinue recombinant factor VIIa (rFVIIa) at least 12 hours before starting concizumab therapy. Discontinue activated prothrombin complex concentrates (aPCC) at least 48 hours before starting concizumab therapy.
The recommended dosing regimen is a loading dose of 1 mg/kg concizumab given once on treatment day one. From day two until determination of individual maintenance dose an initial maintenance dose of 0.20 mg/kg concizumab is administered daily.
From determination of individual maintenance dose onwards concizumab is administered daily.
For further information refer to the Product Information.
Pregnancy category
D
Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
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 caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
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
Alhemo (concizumab) was approved for the following therapeutic use:
Alhemo is indicated where prophylaxis is required to prevent or reduce the frequency of bleeding in patients at least 12 years of age who have haemophilia B (congenital factor IX [FIX] deficiency) with FIX inhibitors.
What is this medicine and how does it work
Concizumab is an antibody against tissue factor pathway inhibitor (TFPI). Physiologically, TFPI dampens the initiation of coagulation by reducing formation of, and directly inhibiting, activated factor X (FXa). Concizumab binds to the Kunitz 2 (K2) domain of TFPI and inhibits these actions of TFPI. For patients with haemophilia, who have inadequate propagation of coagulation due to deficiency of factor VIII (FVIII) or factor IX (FIX), removing TFPI inhibition may allow adequate formation of FXa to generate sufficient thrombin for haemostasis.
As concizumab acts independently from FVIII and FIX, the effect of concizumab is not expected to be influenced by the presence of inhibitory antibodies to FVIII or FIX.
As concizumab has no structural relationship or sequence homology to FVIII or FIX, it is not expected to induce or enhance the development of direct inhibitors to FVIII or FIX.
As concizumab acts independently from FVIII and FIX, the effect of concizumab is not expected to be influenced by the presence of inhibitory antibodies to FVIII or FIX.
As concizumab has no structural relationship or sequence homology to FVIII or FIX, it is not expected to induce or enhance the development of direct inhibitors to FVIII or FIX.
What post-market commitments will the sponsor undertake
- Alhemo(concizumab) is to be included in the Black Triangle Scheme. The PI [Product Information] and CMI [Consumer Medicines Information] for Alhemo 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 Alhemo EU [European Union]-risk management plan (RMP) (version 0.1, dated 8 December 2022, data lock point 30 August 2022), with Australian specific annex (version 0.2, dated 23 March 2023), included with submission PM-2022-03458-1-6, 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).
- 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 data lock point for that report.
- The results from Study 4307 (explorer8) should be submitted for evaluation when available, including any endpoints that involve within-patient comparison of annualised bleeding rates with versus without concizumab prophylaxis. Expected date of availability: fourth quarter of 2023.
- The results of the planned registry-based cohort study should be submitted when available, including an analysis of any thrombosis events and relationship to serum concizumab levels, an analysis of the stability of serum levels with longer term usage, and an analysis of clinical data (if available) regarding catch-up or re-loading doses where treatment is missed or interrupted. Expected date of availability: Interim reports third quarter of 2025, third quarter of 2026, third quarter of 2027, Final report third quarter of 2028.
- Laboratory testing & compliance with Certified Product Details (CPD)
- All batches of Alhemo 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) https://www.tga.gov.au/sites/default/files/pm-argpm-guidance-7.pdf, 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.
Further information
The latest Product Information (PI) and Consumer Medicines Information (CMI) can be found at the Australian Register of Therapeutic Goods (ARTG) search page.
Australian Public Assessment Reports (AusPARs) can be found at the AusPAR search page.
The latest news and updates regarding therapeutic goods regulation can be found at the TGA news page.