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Hepcludex (bulevirtide acetate)
Australian Prescription Medicine Decision Summary
Sponsor
Device/Product name
Hepcludex
Active Ingredient
bulevirtide acetate
Date of decision
Published
Submission type
Type A (New chemical entity)
ATC codes
J05AX28 (J05A: DIRECT ACTING ANTIVIRALS)
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 effectiveness of Hepcludex for the treatment of chronic infection with hepatitis delta virus has been evaluated in 3 randomised, open-label studies: 2 completed Phase 2 studies and 1 ongoing Phase 3 study. In addition, a fourth ongoing, randomised, open-label Phase 2 study is included in the integrated analysis of the clinical safety of Hepcludex.
(visit this page for information on clinical trial types: https://www.australianclinicaltrials.gov.au/about/what-is-a-clinical-trial)
The effectiveness of Hepcludex for the treatment of chronic infection with hepatitis delta virus has been evaluated in 3 randomised, open-label studies: 2 completed Phase 2 studies and 1 ongoing Phase 3 study. In addition, a fourth ongoing, randomised, open-label Phase 2 study is included in the integrated analysis of the clinical safety of Hepcludex.
(visit this page for information on clinical trial types: https://www.australianclinicaltrials.gov.au/about/what-is-a-clinical-trial)
What steps were involved in the decision process
This submission was evaluated under the standard prescription medicines registration process.
| Description | Date |
|---|---|
| Submission dossier accepted and first round evaluation commenced | 1 May 2023 |
| Evaluation completed | 16 January 2024 |
| Delegate’s1 Overall benefit-risk assessment and request for Advisory Committee advice | 3 May 2024 |
| Advisory Committee meeting | 20 June 2024 |
| Registration decision (Outcome) | 22 July 2024 |
| Registration in the ARTG | 30 July 2024 |
| Number of working days from submission dossier acceptance to registration decision2 | 193 |
1. The ‘Delegate’ is the Delegate of the Secretary of the Department of Health and Aged Care who made the final decision to either include the new medicine/indication on the ARTG or reject the submission, under section 25 of the Therapeutic Goods Act.
2. Statutory timeframe for standard submissions is 255 working days
Date of entry onto ARTG
Black triangle scheme
Hepcludex is to be included in the Black Triangle Scheme. The PI and CMI for Hepcludex must include the black triangle symbol ▼ for five years. The black triangle is a visual reminder to encourage health practitioners and patients to report a problem or side effect observed with this medicine.
Dose forms
Powder for injection
Strength
Each vial contains bulevirtide acetate equivalent to 2 mg bulevirtide.
Other ingredients
Mannitol, sodium carbonate, sodium bicarbonate, and may include hydrochloric acid and/or sodium hydroxide for pH adjustment.
Containers
Type 1 clear glass vial, an elastomeric closure, and an aluminum overseal with a flip-off cap.
Pack sizes
Each carton contains 30 vials.
Routes of administration
Subcutaneous injection
Dosage
The recommended dosage in adults is Hepcludex 2 mg once daily administered by subcutaneous injection.
Pregnancy category
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.
There are no adequate and well-controlled studies with HEPCLUDEX in pregnant women. HEPCLUDEX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In nonclinical reproductive toxicity studies, bulevirtide demonstrated no adverse effect on embryofetal development when administered to pregnant rats and rabbits at systemic exposures 12- and 124-fold relative to exposure in humans at the recommended human dose.
There are no adequate and well-controlled studies with HEPCLUDEX in pregnant women. HEPCLUDEX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In nonclinical reproductive toxicity studies, bulevirtide demonstrated no adverse effect on embryofetal development when administered to pregnant rats and rabbits at systemic exposures 12- and 124-fold relative to exposure in humans at the recommended human dose.
What was approved
Hepcludex (bulevirtide acetate) was approved to treat chronic hepatitis delta virus infection in adults with compensated liver disease.
What is this medicine and how does it work
Hepcludex is a hepatitis beta virus-derived synthesised lipopeptide that blocks the entry of hepatitis B virus (HBV) and hepatitis D virus (HDV) into liver cells by binding to and inactivating the essential HBV and HDV entry receptor, sodium taurocholate co-transporting polypeptide (NTCP).
What post-market commitments will the sponsor undertake
Hepcludex is to be included in the Black Triangle Scheme. The PI and CMI for Hepcludex must include the black triangle symbol and mandatory accompanying text for five years. The Black Triangle Scheme identifies new prescription medicines with a black triangle on the medicine information documents. The black triangle is a visual reminder to encourage health practitioners and patients to report a problem or side effect associated with this medicine.
The Hepcludex EU-Risk Management Plan (RMP) (version 3.0, dated 8 November 2022, data lock point 30 July 2022) with Australian Specific Annex (version 0.2, dated June 2023), included with submission PM-2023-01186-1-2, and any subsequent revisions, as agreed with the TGA will be implemented in Australia. An obligatory component of risk management plans is routine pharmacovigilance which 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. Each report must have been prepared within ninety calendar days of the data lock point for that report.
More information
The latest Product Information (PI) and Consumer Medicine Information (CMI) can be found by searching the Australian Register of Therapeutic Goods (ARTG).
Australian Public Assessment Reports (AusPARs) can be found by searching our AusPAR dataset.
The latest news and updates regarding therapeutic goods regulation can be found on our news page.