The following table summarises the key steps and dates for this application.
Data was provided as a rolling submission. Under normal circumstances, the TGA's assessment (for both provisional and general registration) begins once all information to support registration is available. As part of the Department of Health's response to the pandemic, the TGA has agreed to accept rolling data for COVID-19 vaccines and treatments, to enable early evaluation of data as it comes to hand.
This application was evaluated under an Australia-Canada-Singapore-Switzerland-United Kingdom (ACCESS) work sharing agreement to allow for an expedited review of the submission.
|Determination (Provisional)||9 August 2021|
|Submission dossier accepted and first round evaluation commenced||17 August 2021|
|Evaluation completed||30 November 2021|
|Delegate's overall benefit-risk assessment and request for Advisory Committee advice||26 November 2021|
|Sponsor's pre-Advisory Committee response||1 December 2021|
|Advisory Committee meeting||3 December 2021|
|Registration decision (Outcome)||18 January 2022|
|Completion of administrative activities and registration on ARTG||20 January 2022|
|Number of working days from submission dossier acceptance to registration decision*||104|
*Statutory timeframe for standard applications is 255 working days
The recommended dose of Lagevrio in adult patients is 800 mg (four 200 mg capsules) taken orally every 12 hours for 5 days, with or without food.
The safety and efficacy of Lagevrio when administered for periods longer than 5 days have not been established.
Lagevrio should be administered as soon as possible after a diagnosis of coronavirus disease (COVID-19) has been made and within five days of symptom onset in adults who are at risk for progression to severe COVID-19, including hospitalisation or death. Certain medical conditions or other factors may place individual patients at increased risk for progression to severe COVID-19 (see Section 5.1 Pharmacodynamic properties - clinical trials of the Product Information (PI)).
Safety and efficacy of Lagevrio have not been established in patients less than 18 years of age, therefore use in paediatric patients is not recommended (see Section 4.4 Special warnings and precautions for use - paediatric use and Section 5.2 Pharmacokinetic properties - special populations in the PI).
For further information refer to the PI.
Lagevrio (molnupiravir) was approved for the following therapeutic use:
Lagevrio (molnupiravir) has provisional approval for the treatment of adults with COVID 19 who do not require initiation of oxygen due to COVID-19 and who are at increased risk for hospitalisation or death (see section 5.1 Pharmacodynamic properties - Clinical trials).
The decision to approve this indication has been made on the basis of the analysis of efficacy and safety data from a Phase 3 trial. Continued approval of this indication depends on additional data.
- Risk management plan
Molnupiravir (Lagevrio) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Lagevrio must include the black triangle symbol and mandatory accompanying text for 5 years, which starts from the date that the sponsor notifies the TGA of supply of the product.
Any changes to which the sponsor has agreed should be included in a revised RMP and Australian specific annex (ASA). However, irrespective of whether or not they are included in the currently available version of the RMP [risk management plan] document, the agreed changes become part of the risk management system.
The Lagevrio European Union (EU)-RMP (version 0.1, dated 14 October 2021, data lock point 18 September 2021), with ASA (version 0.2, dated 14 December 2021), included with submission PM‑2021‑03679‑1‑2, to be revised to the satisfaction of the TGA, will be implemented in Australia.
The sponsor should provide updates to the RMP and ASA to include ongoing post market safety studies and pharmacovigilance activities within 3 months of approval.
Periodic safety update reports (PSURs) are to be provided in line with the United Kingdom (UK) reference dates and frequency of submissions, until the published list of EU reference dates and frequency of submission of PSURs become available. After that reports should be provided in line with the 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, or the entire period of provisional registration, whichever is longer.
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.
In addition to the submission of PSURs, expedited Lagevrio monthly summary safety reports (including safety data for patients in Australia and reporting of Australia specific safety concerns) are to be provided for the first 6 months post registration, and thereafter at intervals specified by the TGA.
- The sponsor must ensure that the CMI and PI is available in electronic format for health practitioners and patients to download.
- The sponsor is required to provide the TGA with the following information as it arises:
- Data in relation to the activity of molnupiravir against global SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] variants of concern including the omicron variant
- Any additional information from further analysis of the data obtained from [Study] MK-4482-002 Part 2 by second quarter of 2022
- Results of the PK [pharmacokinetic] study in wild type Fisher 344 rats to determine if NHC [n‑hydroxycytidine] or NHC-TP [triphosphate] is detected in the testes. If this study shows that NHC is detected in the testes, the sponsor should also submit the results of the Big Blue rat study
- Results of the 6-month Tg RasH2 mouse carcinogenicity study (initiated in third quarter of 2021)
- Results of the in vitro resistance selection study
- Confirmatory trial data (as identified in the sponsor's plan to submit comprehensive clinical data on the safety and efficacy of the medicine before the end of the 6 years that would start on the day that registration would commence) must be provided for full registration.
Specifically, the sponsor must conduct studies as described in the clinical study plan submitted on fourth quarter of 2021. The following study report(s) should be submitted to TGA:
- MOVe-OUT ([Study] P002), to be submitted first quarter 2022 for safety and efficacy, and 7-month follow up to be submitted third quarter 2022.
Further guidance for sponsors is available on the TGA website.