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Leqvio
Device/Product name
Leqvio
Active Ingredient
Inclisiran
Date of decision
Published
Submission type
New chemical entity
ATC codes
C10AX16
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 Leqvio 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 (ACSS) Consortium, with work-sharing between TGA and Health Canada. Each regulator made independent decisions regarding approval (market authorisation) of the new medicine.
| Description | Date |
|---|---|
| Submission dossier accepted and first round evaluation commenced | 30 September 2020 |
| First round evaluation completed | 21 April 2021 |
| Sponsor provides responses on questions raised in first round evaluation | 21 April 2021 |
| Second round evaluation completed | 17 June 2021 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 30 June 2021 |
| Sponsor's pre-Advisory Committee response | 13 July 2021 |
| Advisory Committee meeting | 5 and 6 August 2021 |
| Registration decision (Outcome) | 14 September 2021 |
| Completion of administrative activities and registration on ARTG | 14 September 2021 |
| Number of working days from submission dossier acceptance to registration decision* | 236 |
*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
Solution for injection
Strength
284 mg/1.5 mL (equivalent to 300 mg inclisiran sodium)
Other ingredients
Water for injection, sodium hydroxide (for pH adjustment) and phosphoric acid (for pH adjustment).
Containers
Pre-filled syringe
Pack sizes
One
Routes of administration
Subcutaneous injection
Dosage
The recommended dose of Leqvio is 284 mg administered as a single subcutaneous injection: initially, again at 3 months, followed by every 6 months.
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
Leqvio (inclisiran) was approved for the following therapeutic use:
Leqvio is indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with heterozygous familial hypercholesterolaemia, atherosclerotic cardiovascular disease, or at high risk of a cardiovascular event:
- in combination with a statin or statin with other lipid‐lowering therapies in patients unable to reach LDL‐C goals with the maximum tolerated dose of a statin or,
- alone or in combination with other lipid‐lowering therapies in patients who are statin-intolerant
What is this medicine and how does it work
Inclisiran is a cholesterol-lowering double-stranded small interfering ribonucleic acid (siRNA), conjugated on the sense strand with triantennary N-acetylgalactosamine (GalNAc) to facilitate uptake by hepatocytes. In hepatocytes, inclisiran utilises the RNA interference mechanism and directs catalytic breakdown of messenger RNA (mRNA) for proprotein convertase subtilisin/kexin type 9. This increases low density lipoprotein cholesterol (LDL-C) receptor recycling and expression on the hepatocyte cell surface, which increases LDL-C uptake and lowers LDL-C levels in the circulation.
What post-market commitments will the sponsor undertake
- Leqvio (inclisiran) is to be included in the Black Triangle Scheme. The PI and CMI for Leqvio 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 inclisiran European Union (EU)-Risk Management Plan (RMP) (version 1.0, dated 12 October 2020, data lock point 17 September 2019), with Australian Specific Annex (version 1.2, dated 5 August 2021), included with submission PM-2020-04160-1-3, to be revised to the satisfaction of 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.
Analysis of the following inclisiran use safety topics is to be included in PSUR submissions to the TGA: hepatotoxicity; long-term immunogenicity; new onset diabetes mellitus and worsening of pre-existing diabetes mellitus; and use in patients with severe renal impairment.
- Final study reports for ORION-3 and ORION-8 must be submitted to the TGA for review on completion.
- For all injectable products the Product Information must be included with the product as a package insert.