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Trecondi
Sponsor
ARTGs
Device/Product name
Trecondi
Active Ingredient
Treosulfan
Date of decision
Published
Submission type
New chemical entity
ATC codes
LO1AB02
Decision
Approved
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 Trecondi 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) | 11 June 2021 |
| Submission dossier accepted and first round evaluation commenced | 2 August 2021 |
| First round evaluation completed | 22 December 2021 |
| Sponsor provides responses on questions raised in first round evaluation | 28 February 2022 |
| Second round evaluation completed | 18 May 2022 |
| Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice | 29 June 2022 |
| Sponsor’s pre-Advisory Committee response | 15 July 2022 |
| Advisory Committee meeting | 4 and 5 August 2022 |
| Registration decision (Outcome) | 19 September 2022 |
| Completion of administrative activities and registration on ARTG | 23 September 2022 |
| Number of working days from submission dossier acceptance to registration decision* | 221 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
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
Dose forms
Powder for solution for infusion
Strength
1 g and 5 g
Other ingredients
None
Containers
Vial
Pack sizes
1 and 5
Routes of administration
Intravenous infusion
Dosage
Administration of treosulfan should be supervised by a physician experienced in conditioning treatment followed by allogeneic hematopoietic stem cell transplantation (alloHSCT).
Adults with AML or MDS
Treosulfan is given in combination with fludarabine.
The recommended dose and schedule of administration is:
- Treosulfan 10 g/m² body surface area (BSA) per day as a two-hour intravenous infusion, given on three consecutive days (day -4, -3, -2) before stem cell infusion (day 0). The total treosulfan dose is 30 g/m²;
- Fludarabine 30 mg/m² BSA per day as a 0.5-hour intravenous infusion, given on five consecutive days (day -6, -5, -4, -3, -2) before stem cell infusion (day 0). The total fludarabine dose is 150 mg/m²;
- Treosulfan should be administered before fludarabine on days -4, -3, -2 (FT10 regimen).
Paediatric population aged 1 month and older with malignant and non-malignant haematological diseases
Treosulfan is given in combination with fludarabine, with thiotepa (intensified regimen; FT10-14TT regimen) or without thiotepa (FT10-14 regimen).
The dose and schedule of administration in paediatric population is based on body surface area and use of medicine such as fludarabine and thiotepa. For futher information refers to Section 4.2 Dose and method of administration in the Product Information.
The safety and efficacy of treosulfan in children less than 1 month of age has not yet been established.
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
Trecondi (treosulfan) was approved for the following therapeutic use:
Adults with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS)
Trecondi (treosulfan) is indicated in combination with fludarabine as part of conditioning treatment prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult patients with AML or MDS at increased risk for standard conditioning therapies.
Paediatric patients aged 1 month and older with malignant and non-malignant haematological diseases
Trecondi (treosulfan) is indicated in combination with fludarabine, with or without thiotepa, as part of conditioning treatment prior to allogeneic haematopoietic stem cell transplantation (alloHSCT) in paediatric patients older than one month with malignant and non-malignant diseases.
What is this medicine and how does it work
Treosulfan is a prodrug of a bifunctional alkylating agent with cytotoxic activity to haematopoietic precursor cells. The activity of treosulfan is due to the spontaneous conversion into a mono-epoxide intermediate and L-diepoxybutane (see section 5.2 of Product Information).
The epoxides formed alkylate nucleophilic centres of deoxyribonucleic acid (DNA) and are able to induce DNA cross-links which are considered responsible for the stem cell depleting and antineoplastic effects.
The epoxides formed alkylate nucleophilic centres of deoxyribonucleic acid (DNA) and are able to induce DNA cross-links which are considered responsible for the stem cell depleting and antineoplastic effects.
What post-market commitments will the sponsor undertake
- Trecondi (treosulfan) is to be included in the Black Triangle Scheme. The PI [Product Information] and CMI [Consumer Medicine Information] for Trecondi 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 Trecondi global risk management plan (RMP) (version 0.4, dated 30 December 2020, data lock point 19 June 2020), with Australia specific annex (version 0.1, dated April 2021), included with Submission PM-2021-02707-1-6, 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).
Reports are to be provided in line with the current published list of EU [European Union] 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.
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.
- For all injectable products the Product Information must be included with the product as a package insert.