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Device/Product name
Zepzelca
Active Ingredient
Lurbinectedin
Date of decision
Published
Submission type
New chemical entity
ATC codes
L01XX69
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 Zepzelca 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 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 17 February 2020
Designation - Provisional 29 April 2020
Submission dossier accepted and first round evaluation commenced 2 June 2020
First round evaluation completed 2 November 2020
Sponsor provides responses on questions raised in first round evaluation 21 December 2020
Second round evaluation completed 12 February 2021
Delegate's overall benefit-risk assessment 8 September 2021
Sponsor's pre-Advisory Committee response Not applicable
Advisory Committee meeting Not applicable
Registration decision (Outcome) 10 September 2021
Completion of administrative activities and registration on ARTG 13 September 2021
Number of working days from submission dossier acceptance to registration decision* 153

*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
Powder for injection
Strength
4 mg
Other ingredients
(S)-lactic acid, sucrose and sodium hydroxide
Containers
Vial
Pack sizes
One
Routes of administration
Intravenous infusion
Dosage

The recommended dose is 3.2 mg/m2 by intravenous infusion over 60 minutes, repeated once every 21 days until disease progression or unacceptable toxicity.

Only administer Zepzelca to patients with an absolute neutrophil count above 1.5 x 109/L, and a platelet count above 100 x 109/L.

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

Zepzelca (lurbinectedin) was approved for the following therapeutic use:

Zepzelca is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) that has progressed on or after prior platinum-containing therapy. This indication was approved via the provisional approval pathway, based on objective response rate and duration of response in a single arm trial. Continued approval for this indication depends on verification and description of clinical benefit in a confirmatory trial.
What is this medicine and how does it work
Lurbinectedin is an alkylating drug that binds guanine residues in the minor groove of deoxyribonucleic acid (DNA), forming adducts and resulting in a bending of the DNA helix towards the major groove. Adduct formation triggers a cascade of events that can affect the subsequent activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in perturbation of the cell cycle and eventual cell death.Lurbinectedin inhibited human monocyte activity in vitro and reduced macrophage infiltration in implanted tumours in mice.
What post-market commitments will the sponsor undertake
  • Zepzelca (lurbinectedin) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Zepzelca must include the black triangle symbol and mandatory accompanying text for the products entire period of provisional registration.
  • The lurbinectedin core European Union (EU)-risk management plan (RMP) (version 0.2, dated 15 January 2020, data lock point 17 April 2020), with Australian specific annex (ASA) (version 0.3, dated September 2021), included with Submission PM-2020-02181-1-4, 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 (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 0.3 (September 2021) of the ASA. The following study report(s) should be submitted to TGA:

    • PM1183-C-008-21, by first quarter of 2026

    Further guidance for sponsors is available on the TGA website.

  • For all injectable products the PI must be included with the product as a package insert.

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