Retevmo
Registration timeline
This evaluation was facilitated through Project Orbis, an initiative of the United States (US) Food and Drug Administration (FDA) Oncology Center of Excellence (OCE). Under this project, the FDA, Health Canada (HC), Swissmedic and the TGA collaboratively reviewed the application. This innovative evaluation process provided a framework for process alignment and management of evaluation issues in real-time across jurisdictions.
Each regulator agency maintained its regulatory process to make independent decisions about the approval (market authorisation).
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Description |
Date |
|---|---|
|
Determination (Provisional) |
28 March 2022 |
|
Submission dossier accepted and first round evaluation commenced
|
1 August 2022 |
|
First round evaluation completed |
13 January 2023 |
|
Sponsor provides responses on questions raised in first round evaluation |
21 February 2023 |
|
Second round evaluation completed |
31 March 2023 |
|
Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice |
21 April 2023 |
|
Sponsor’s pre-Advisory Committee response |
12 May 2023 |
|
Advisory Committee meeting |
1 and 2 June 2023 |
|
Registration decision (Outcome) |
27 June 2023 |
|
Completion of administrative activities and registration on ARTG |
3 July 2023 |
|
Number of working days from submission dossier acceptance to registration decision* |
181 |
*Statutory timeframe for standard applications is 255 working days
For 40 mg-
Ammonia, butan-1-ol, colloidal anhydrous silica, ethanol absolute, gelatin, iron oxide black, isopropyl alcohol, microcrystalline cellulose, potassium hydroxide, propylene glycol, purified water, shellac and titanium dioxide.
For 80 mg-
Ammonia, brilliant blue FCF, butan-1-ol, colloidal anhydrous silica, ethanol absolute, gelatin, iron oxide black, isopropyl alcohol, microcrystalline cellulose, potassium hydroxide, propylene glycol, purified water, shellac and titanium dioxide.
Retevmo therapy should be initiated and supervised by physicians experienced in the use of anti-cancer therapies.
The recommended dose of Retevmo based on body weight is:
- Less than 50 kg: 120 mg twice daily.
- 50 kg or greater: 160 mg twice daily.
If a patient vomits or misses a dose, the patient should be instructed to take the next dose at its scheduled time; an additional dose should not be taken. Treatment should be continued until disease progression or unacceptable toxicity.
For further information refer to the Product Information.
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.
Retevmo (selpercatinib) was approved for the following therapeutic use:
The provisionally approved new indication(s) for the medicine(s) are:
Retevmo has provisional approval for the treatment of adult patients with locally advanced or metastatic RET fusion positive non-small cell lung cancer (NSCLC).
The decision to approve this indication has been made on the basis of objective response rate (ORR) and duration of response (DOR) from a single arm study. Continued approval of this indication depends on verification and description of benefit in a confirmatory trial.
In RET enzyme assays, selpercatinib inhibits the kinase activity of RET, RET-V804L, RET-V804M, RET-A883F, RET-S904F, RET-A764T, RET-S891A and RET-M918T with half maximal inhibitory concentration (IC50) values of 0.20 nM to 2.21 nM. In kinase screening assays, selpercatinib at a concentration of 100 nM inhibits only six of 329 non-RET kinases by more than 50% of the control. Among these, selpercatinib inhibits two kinases with IC50 values within 35-fold of RET: Fms-related tyrosine kinase 4 (FLT4) (0.7-fold in an enzyme-based assay and 8- fold in a cell-based assay); and FLT1 (1.6-fold). Selpercatinib inhibits platelet derived growth factor receptor beta (PDGFRB) with an IC50 value of 2100 nM, and janus kinase inhibitor (JAK1, JAK2, JAK3), TRKA, and TRKC with IC50 values greater than 5000 nM in enzyme assays.
Selpercatinib demonstrates in vitro inhibition of human cancer cell lines derived from multiple tumour types harbouring RET fusion genes and RET mutations with EC50 values equal to 10 nM or less. In in vivo mouse studies, selpercatinib demonstrates inhibition of tumor growth in RET fusion and RET mutant cancer cell lines, patient-derived RET fusion xenograft models, and a patient-derived RET fusion xenograft model harbouring a RET V804M mutation. Selpercatinib also exhibits intracranial anti-tumour activity of patient-derived RET fusion xenograft tumours implanted directly into the brain of mice.
In additional radioligand binding assays, selpercatinib inhibits two out of 54 non-kinase targets at a concentration of 1 μM: 5-HT transporter (70.2%) and α2c receptor (51.7%).
- Retevmo (selpercatinib) is to be included in the Black Triangle Scheme. The PI [Product Information] and CMI [Consumer Medicines Information] for Retevmo must include the black triangle symbol and mandatory accompanying text for five years, or the product’s entire period of provisional registration, whichever is longer.
- The Retevmo EU [European Union]-risk management plan (RMP) (version 3.2, dated 2 November 2022, data lock point 15 June 2021), with Australia specific annex (version 2.0, dated 30 January 2023), included with Submission PM-2022-02343-1-4, 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, 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 (revision 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.
- Specifically, the sponsor must conduct studies as described in the clinical study plan in version 2.0 (dated 30 January 2023) of the Australia specific annex. The following study report(s) should be submitted to the TGA:
- Study J2G-OX-JZJA (LIBRETTO-001 trial) by 2024
- Study J2G-MCJZJC (LIBRETTO-431 trial) by 2026
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.