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Pemazyre
ARTGs
Device/Product name
Pemazyre
Active Ingredient
Pemigatinib
Date of decision
Published
Submission type
New chemical entity
ATC codes
L01EN02
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 Pemazyre 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.
| Description | Date |
|---|---|
| Designation (Orphan) | 21 April 2021 |
| Determination (Provisional) | 21 April 2021 |
| Submission dossier accepted and first round evaluation commenced | 30 September 2021 |
| First round evaluation completed | 26 May 2022 |
| Sponsor provides responses on questions raised in first round evaluation | 25 April 2022 |
| Second round evaluation completed | 21 July 2022 |
| Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice | 30 June 2022 |
| Sponsor’s pre-Advisory Committee response | 15 July 2022 |
| Advisory Committee meeting | 4 and 5 August 2022 |
| Registration decision (Outcome) | 12 September 2022 |
| Completion of administrative activities and registration on ARTG | 14 September 2022 |
| Number of working days from submission dossier acceptance to registration decision* | 194 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
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
Tablet
Strength
4.5 mg, 9 mg and 13.5 mg
Other ingredients
Microcrystalline cellulose, sodium starch glycollate type A and magnesium stearate
Containers
Blister pack
Pack sizes
14 and 28
Routes of administration
Oral
Dosage
Therapy should be initiated by a physician experienced in the diagnosis and treatment of patients with biliary tract cancer.
Fibroblast growth factor receptor 2 (FGFR2) fusion positivity status must be known prior to initiation of Pemazyre therapy.
The recommended dose is 13.5 mg Pemazyre taken once daily for 14 days followed by 7 days off-therapy.
Treatment should be continued as long as the patient does not show evidence of disease progression or unacceptable toxicity.
Dose modifications or interruption of dosing should be considered when Pemazyre is co-administered with strong or moderate cytochrome P450 3A4 (CYP3A4) inhibitors and for the management of toxicities. Treatment should be permanently discontinued if patient is unable to tolerate 4.5 mg Pemazyre once daily (see Sections 4.2 Dose and method of administration, Section 4.4 Special warnings and precautions for use and Section 4.5 Interactions with other medicines and other forms of interactions of the Product Information).
For further information refer to the Product Information.
Pregnancy category
D
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.
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.
What was approved
Pemazyre (pemigatinib) was approved for the following therapeutic use:
Pemigatinib has provisional approval in Australia for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that has progressed after at least one prior line of systemic therapy. The decision to approve this indication has been made on the basis of overall response rate (ORR) and duration of response (DOR). Continued approval of this indication depends on verification and description of benefit in confirmatory trial(s).
What is this medicine and how does it work
Pemigatinib is a small molecule kinase inhibitor of fibroblast growth factor receptor (FGFR)1, 2 and 3 with half maximal inhibitory concentration (IC50) values of less than 2 nM. Pemigatinib also inhibited FGFR4 in vitro at a concentration approximately 100 times higher than those that inhibit FGFR1, 2, and 3. It inhibits FGFR1, 2 and 3 phosphorylation and signalling and decreases cell viability in cancer cell lines with activating FGFR genetic alterations, including point mutations, amplifications, and fusions or rearrangements that resulted in constitutive activation of FGFR signalling. FGFR2 fusions or rearrangements are strong oncogenic drivers and are the most common FGFR alteration occurring, almost exclusively, in 10 to 16% of intrahepatic cholangiocarcinoma. Constitutive FGFR signalling can support the proliferation and survival of malignant cells. Pemigatinib exhibited anti-tumour activity in mouse xenograft models of human tumours with FGFR1, FGFR2, or FGFR3 alterations resulting in constitutive FGFR activation including a patient-derived xenograft model of cholangiocarcinoma that expressed an oncogenic FGFR2 transformer-2 beta homolog (TRA2b) fusion protein.
What post-market commitments will the sponsor undertake
- Pemazyre (pemigatinib) is to be included in the Black Triangle Scheme. The PI [Product Information] and CMI [Consumer Medicine Information] for Pemazyre 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 Pemazyre EU [European Union]-risk management plan (RMP) (version 1.4, dated 29 January 2021, data lock point 22 March 2019), with Australia specific annex (version 0.3, dated April 2022), included with Submission PM-2021-03777-1-4, 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 this 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.
- [The sponsor to] submit the results of the confirmatory study, FIGHT‑302 (INCB 54828‑302), a Phase III study comparing the efficacy and safety of pemigatinib [versus] gemcitabine plus cisplatin chemotherapy in adults with unresectable or metastatic cholangiocarcinoma with FGFR2 [fibroblast growth factor receptor 2] rearrangement.
- [The sponsor to] submit an updated PK [pharmacokinetic]/PD [pharmacodynamic] modelling analysis for evaluation.