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Truseltiq
Sponsor
ARTGs
348760, 348761, 348762, 348763
348760, 348761, 348762, 348763
348760, 348761, 348762, 348763
348760, 348761, 348762, 348763
Device/Product name
Truseltiq
Active Ingredient
Infigratinib (as phosphate)
Date of decision
Published
Submission type
New chemical entity
ATC codes
Not yet assigned
Decision
Approved for provisional registration
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 Truseltiq 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 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) 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).
| Description | Date |
|---|---|
| Designation (Orphan and Provisional) | 30 October 2020 |
| Submission dossier accepted and first round evaluation commenced | 4 January 2021 |
| First round evaluation completed | 3 June 2021 |
| Sponsor provides responses on questions raised in first round evaluation | 2 July 2021 |
| Second round evaluation completed | 24 August 2021 |
| Delegate's overall benefit-risk assessment | 6 October 2021 |
| Sponsor's pre-Advisory Committee response | Not Applicable |
| Advisory Committee meeting | Not Applicable |
| Registration decision (Outcome) | 2 November 2021 |
| Completion of administrative activities and registration on ARTG | 5 November 2021 |
| Number of working days from submission dossier acceptance to registration decision* | 189 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Original publication date
Black triangle scheme
Yes.As a provisionally registered product, this medicine will remain in the Black Triangle Scheme for the duration of its provisional registration.
Dose forms
Hard capsule
Strength
25 mg, 100 mg, and 25 mg + 100 mg (composite pack)
Other ingredients
Lactose monohydrate, microcrystalline cellulose, crospovidone, hypromellose, magnesium stearate (from vegetable source), colloidal anhydrous silica, gelatin (bovine), titanium dioxide, iron oxide red (100 mg capsules only), iron oxide yellow (100 mg capsules only), iron oxide black (25 mg capsules only) and TekPrint SW-9049 black ink
Containers
Blister pack
Pack sizes
21 (100 mg capsules), 42 (25 mg capsules), 42 (composite pack of 21 x 25 mg capsules and 21 x 100 mg capsules) and 63 (25 mg capsules)
Routes of administration
Oral
Dosage
The recommended dose of Truseltiq is 125 mg (one 100 mg hard capsule and one 25 mg hard capsule) orally once daily for 21 consecutive days followed by 7 days off therapy, in 28 day cycles. Continue treatment until disease progression or unacceptable toxicity.
For further information refer to the Product Information.
Pregnancy category
DDrugs 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.
What was approved
Truseltiq (infigratinib) was approved for the following therapeutic use:
Truseltiq infigratinib has provisional approval in Australia for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement (see Section 4.2 Dose and method of administration). The decision to approve this indication has been made on the basis of overall response rate and duration of response in a single arm trial. Continued approval of this indication depends on verification and description of benefit in confirmatory trials.
What is this medicine and how does it work
Infigratinib is a small molecule kinase inhibitor that targets fibroblast growth factor receptor (FGFR)1, FGFR2 and FGFR3 with in vitro half-maximal inhibitory concentration (IC50) values of 1.1, 1.0, and 2.0 nanomolar (nM), respectively. In vitro, infigratinib inhibited the activity of FGFR1 to FGFR3, but not FGFR4, kinase insert domain receptor (KDR) and other kinases, at clinically relevant concentrations. The major active metabolites of infigratinib, BHS697 and CQM157, showed similar in vitro binding activity as infigratinib towards FGFR1 to FGFR3, with similar less potent activity toward FGFR4, in binding affinity studies. Infigratinib inhibited FGFR1 to FGFR3 phosphorylation and signalling and decreased cell viability in cancer cell lines with activating FGFR amplifications, mutations and fusions that resulted in constitutive activation of FGFR signalling. Constitutive FGFR signalling can support the proliferation and survival of malignant cells. Infigratinib exhibited anti-tumour activity in mouse and rat xenograft models of human tumours with activating FGFR1, FGFR2, or FGFR3 alterations, including two patient-derived xenograft models of cholangiocarcinoma that expressed distinct FGFR2 fusion proteins. Infigratinib demonstrated brain-to-plasma concentration ratios (based on antibiotics area under the plasma concentration time curve from time zero to infinity (AUC0-inf)) of 0.682 in rats after a single oral dose.
What post-market commitments will the sponsor undertake
- Truseltiq (infigratinib) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Truseltiq must include the black triangle symbol and mandatory accompanying text for the product’s entire period of provisional registration.
- Periodic safety update reports and risk management plan conditions.
Medicines with a risk management plan
The infigratinib core-risk management plan (RMP) (version 1.0, dated 20 September2021, data lock point 1 March 2021) with Australian specific annex (version 1.2, dated 21 September 2021), included with Submission PM-2020-06031-1-4, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.
An obligatory component of RMP 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 (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.
- 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.
Specifically, the sponsor must conduct studies as described in the clinical study plan in version 1.0 (dated 23 June 2021) of the Australia specific annex. The following study report(s) should be submitted to the TGA:
- Study CBGJ398X2204, ClinicalTrials.gov identifier NCT02150967, by the second quarter in 2023
- Study QBGJ398-301, the PROOF trial, by the second quarter in 2027.
Further guidance for sponsors is available on the TGA website.