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The Australian Prescription Medicine Decision Summary provides a short overview of the TGA's evaluation process leading to the registration of a new prescription medicine on the Australian Register of Therapeutic Goods (ARTG).
More in-depth information about the evaluation will be available in the Australian Public Assessment Report (AusPAR) for a particular prescription medicine, which can be found on the AusPAR search page once published.
Australian prescription medicine decision summary
|Submission type|| |
New chemical entity
|Product name|| |
|Active ingredients|| |
|ATC codes|| |
|Date of decision|| |
19 March 2020
|Date of entry onto ARTG|| |
20 March 2020
|ARTG numbers|| |
315020, 315055, 315064
|Black Triangle Scheme|| |
Yes. This product will remain in the scheme for 5 years, starting on the date the product is first supplied in Australia
Novartis Pharmaceuticals Australia Pty Ltd
|Sponsor address|| |
54 Waterloo Road Macquarie Park, NSW 2113
|Dose forms|| |
Film coated tablet
50 mg, 150 mg, 200 mg
|Other ingredients|| |
Piqray tablets contain the following inactive ingredients: microcrystalline cellulose, mannitol, sodium starch glycollate, hypromellose, magnesium stearate (vegetable source), macrogol, iron oxide red CI77491, iron oxide black CI77499, titanium dioxide (E171), and purified talc.
|Pack sizes|| |
50 mg and 200 mg film coated tablets composite pack: 14 day* or 28 day calendar packs containing 28 film coated tablets (fourteen 50 mg and fourteen 200 mg) or 56 film coated tablets (twenty eight 50 mg and twenty eight 200 mg).
150 mg film coated tablets pack: 14 day* or 28 day calendar packs containing 28 or 56 film coated tablets.
200 mg film coated tablets pack: 14 day* or 28 day calendar packs containing 14 or 28 film coated tablets.
*Not all pack sizes are supplied.
|Routes of administration|| |
Treatment with Piqray should be initiated by a physician experienced in the use of anticancer Patients with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer should be selected for treatment with Piqray, based on the presence of a phosphatidylinositol 3-kinase catalytic alpha subunit (PIK3CA) mutation in tumour or plasma specimens, using a validated test. If a mutation is not detected in a plasma specimen, test tumour tissue if available.
The safety and efficacy of alpelisib in combination with a gonadotropin-releasing hormone (GnRH) agonist in pre- or peri-menopausal women has not been established. There was no treatment benefit demonstrated in patients without PIK3CA mutations, in the Phase III clinical study (see Section 5.1 Pharmacodynamic properties).
The recommended dose of Piqray is 300 mg (two 150 mg film coated tablets) taken orally, once daily. Piqray should be taken immediately following food, at approximately the same time each day (see Section 5.1 Pharmacodynamic properties and Section 4.5 Interactions). The maximum recommended daily dose of Piqray is 300 mg. If patient vomits after taking the Piqray dose, the patient should not take an additional dose on that day, and should resume the usual dosing schedule the next day, at the usual time.
When co-administered with Piqray, the recommended dose of fulvestrant is 500 mg administered intramuscularly on Days 1, 15 and, 29, and once monthly thereafter. Please refer to the full product information of fulvestrant.
Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs. Dosing modifications may be necessary to improve tolerability.
For further information refer to the Product Information.
|Pregnancy category|| |
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.
Piqray (alpelisib) was approved for the following therapeutic use:
Piqray in combination with fulvestrant, is indicated for the treatment of postmenopausal women, and men, with hormone receptor positive, HER2-negative, advanced or metastatic breast cancer with a PIK3CA mutation as detected by a validated test following progression on or after an endocrine-based regimen.
Alpelisib is a class I phosphatidylinositol 3-kinase (PI3K) inhibitor with higher activity against PI3Kα than other members of class I PI3K. Class I PI3K lipid kinases are key components of the PI3K/AKT/mammalian target of rapamycin (mTOR) signalling pathway.
Gain-of-function mutations in the gene encoding the catalytic α-subunit of PI3K (PIK3CA) lead to activation of PI3Kα manifested by increased lipid kinase activity, growth-factor independent activation of Akt-signaling, cellular transformation and the generation of tumours in preclinical models.
In vitro, alpelisib treatment inhibited the phosphorylation of PI3K downstream targets Akt as well as its various downstream effectors in breast cancer cells and showed activity towards cell lines harboring a PIK3CA mutation.
In vivo, alpelisib showed good tolerability as well as dose-and time-dependent inhibition of the PI3K/Akt pathway and dose-dependent tumour growth inhibition in relevant tumour xenograft models, including models of breast cancer.
PI3K inhibition by alpelisib treatment has been shown to induce an increase in estrogen receptor (ER) transcription in breast cancer cells, therefore, sensitizing these cells to ER inhibition by fulvestrant treatment. Combination of alpelisib and fulvestrant demonstrated increased anti-tumour activity than either treatment alone in xenograft models derived from ER+, PIK3CA mutated breast cancer cell lines (MCF-7 and KPL1).
The following table summarises the key steps and dates for this application.
|Submission dossier accepted and first round evaluation commenced||1 April 2019|
|First round evaluation completed||23 October 2019|
|Sponsor provides responses on questions raised in first round evaluation||24 December 2019|
|Second round evaluation completed||17 February 2020|
|Delegate's overall benefit-risk assessment||2 January 2020|
|Sponsor's pre-Advisory Committee response||Not applicable|
|Advisory Committee meeting||Not applicable|
|Registration decision (Outcome)||19 March 2020|
|Completion of administrative activities and registration on ARTG||20 March 2020|
|Number of working days from submission dossier acceptance to registration decision*||195|
*Statutory timeframe for standard applications is 255 working days
- Piqray (alpelisib) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Piqray must include the black triangle symbol and mandatory accompanying text for five years, which starts from the date that the sponsor notifies the TGA of supply of the product.
- The Piqray European Union-Risk Management Plan (EU-RMP) (version 1.0, dated 4 December 2018, data lock point 12 June 2018), with Australian specific Annex (version 1.0, dated 7 February 2019), included with submission PM-2019-00401-1-4, 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 this 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. The annual submission may be made up of two PSURs each covering six months. If the sponsor wishes, the six monthly reports may be submitted separately as they become available.
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.
- Submit the final clinical study report for SOLAR-1 when available.
- Assessment of the transport potential for bile salt export pump (BSEP), multidrug and toxin extrusion 1 (MATE1) and multidrug resistance-associated protein 2 (MRP2) in the liver system is to be performed as a post-marketing commitment.