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Vazkepa
Sponsor
ARTGs
Device/Product name
Vazkepa
Active Ingredient
Icosapent ethyl
Date of decision
Published
Submission type
New chemical 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 Vazkepa 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 B (COR-B) application.
|
Description |
Date |
|
Submission dossier accepted and first round evaluation commenced |
15 February 2022 |
|
First round evaluation completed |
31 May 2022 |
|
Sponsor provides responses on questions raised in first round evaluation |
24 June 2022 |
|
Second round evaluation completed |
11 August 2022 |
|
Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice |
2 September 2022 |
|
Sponsor’s pre-Advisory Committee response |
19 September 2022 |
|
Advisory Committee meeting |
6 and 7 October 2022 |
|
Registration decision (Outcome) |
2 November 2022 |
|
Completion of administrative activities and registration on ARTG |
8 November 2022 |
|
Number of working days from submission dossier acceptance to registration decision* |
157 |
* The COR-B process has a 175 working day evaluation and decision timeframe.
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
Soft capsule
Strength
998 mg
Other ingredients
dl-alpha-tocopherol, gelatin, glycerol, hypromellose, lecithin, maltitol solution, medium chain triglycerides, propylene glycol, purified water, sorbitol solution (70 per cent) (non-crystallising), and titanium dioxide
Containers
Blister pack and bottle
Pack sizes
8 (blister pack) and 120 (bottle)
Routes of administration
Oral
Dosage
The recommended daily oral dose is 4 capsules taken as two 998 mg capsules twice daily.
If a dose is missed, patients should take it as soon as they remember. However, if one daily dose is missed, the next dose should not be doubled.
For further information refer to the Product Information.
Pregnancy category
B1
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 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.
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 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
Vazkepa (icosapent ethyl) was approved for the following therapeutic use:
Vazkepa is indicated to reduce the risk of cardiovascular events in adult statin- treated patients at high cardiovascular risk with elevated triglycerides (≥ 1.7 mmol/L) and
- established cardiovascular disease, or
- diabetes, and at least one other cardiovascular risk factor.
What is this medicine and how does it work
Icosapent ethyl is a stable ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid (EPA). The mechanisms of action contributing to reduction of cardiovascular events with icosapent ethyl are not completely understood. The mechanisms are likely multi-factorial including improved lipoprotein profile with reduction of triglyceride-rich lipoproteins, anti-inflammatory, and antioxidant effects, reduction of macrophage accumulation, improved endothelial function, increased fibrous cap thickness/stability, and antiplatelet effects.
Each of these mechanisms can beneficially alter the development, progression, and stabilisation of atherosclerotic plaque, as well as the implications of plaque rupture, and preclinical and clinical studies support such benefits with EPA. Systemic and localised anti-inflammatory effects of EPA may result from displacement of pro-inflammatory arachidonic acid (AA), directing catabolism away from eicosanoids (2-series prostaglandins and thromboxanes, and 4-series leukotrienes) to non- or anti-inflammatory mediators. However, the direct clinical meaning of individual findings is not clear.
Icosapent ethyl improves the lipoprotein profile by suppressing cholesterol-, fatty acid- and triglyceride (TG)- synthesising enzymes, increasing fatty acid β-oxidation, and reducing microsomal triglyceride transfer (MTP) protein, resulting in decreased hepatic TG and very low-density lipoprotein (VLDL) synthesis and release.
Icosapent ethyl also increases expression of lipoprotein lipase leading to increased TG removal from circulating VLDL and chylomicron particles. In patients with elevated TG levels, icosapent ethyl lowers TG, VLDL, remnant lipoprotein cholesterol, and levels of inflammatory markers such as C-reactive protein. However, TG reduction appears to provide only a minor contribution to the reduction in risk of cardiovascular events with icosapent ethyl.
Each of these mechanisms can beneficially alter the development, progression, and stabilisation of atherosclerotic plaque, as well as the implications of plaque rupture, and preclinical and clinical studies support such benefits with EPA. Systemic and localised anti-inflammatory effects of EPA may result from displacement of pro-inflammatory arachidonic acid (AA), directing catabolism away from eicosanoids (2-series prostaglandins and thromboxanes, and 4-series leukotrienes) to non- or anti-inflammatory mediators. However, the direct clinical meaning of individual findings is not clear.
Icosapent ethyl improves the lipoprotein profile by suppressing cholesterol-, fatty acid- and triglyceride (TG)- synthesising enzymes, increasing fatty acid β-oxidation, and reducing microsomal triglyceride transfer (MTP) protein, resulting in decreased hepatic TG and very low-density lipoprotein (VLDL) synthesis and release.
Icosapent ethyl also increases expression of lipoprotein lipase leading to increased TG removal from circulating VLDL and chylomicron particles. In patients with elevated TG levels, icosapent ethyl lowers TG, VLDL, remnant lipoprotein cholesterol, and levels of inflammatory markers such as C-reactive protein. However, TG reduction appears to provide only a minor contribution to the reduction in risk of cardiovascular events with icosapent ethyl.
What post-market commitments will the sponsor undertake
- Vazkepa (icosapent ethyl) is to be included in the Black Triangle Scheme. The PI [Product Information] and CMI [Consumer Medicines Information] for Vazkepa 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 Vazkepa EU [European Union]-risk management plan (RMP) (version 0.4, dated 18 December 2020, data lock point 6 September 2018), with Australia specific annex (version 0.2, dated June 2022), included with Submission PM-2021-05861-1-3, 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 (revision 1), Part VII.B structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration.