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Koselugo
Sponsor
ARTGs
345972 and 345973
345972 and 345973
Device/Product name
Koselugo
Active Ingredient
Selumetinib sulfate
Date of decision
Published
Submission type
New chemical entity
ATC codes
L01EE04
Decision
Approved
What was the decision based on
The decision was based on nonclinical (pharmacology and toxicology), clinical (pharmacology, safety and efficacy) and risk management plan information submitted by the sponsor. The benefit-risk profile of Koselugo was considered favourable for the therapeutic use approved.
What steps were involved in the decision process
Registration timeline
This evaluation was facilitated through Project Orbis, an initiative of the United States (US) Food and Drug Administration (FDA) Oncology Centre 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) | 30 July 2020 |
| Submission dossier accepted and first round evaluation commenced | 30 November 2020 |
| First round evaluation completed | 30 April 2021 |
| Sponsor provides responses on questions raised in first round evaluation | 29 June 2021 |
| Second round evaluation completed | 30 July 2021 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 30 August 2021 |
| Sponsor's pre-Advisory Committee response | 14 September 2021 |
| Advisory Committee meeting | 30 September and 1 October 2021 |
| Registration decision (Outcome) | 29 November 2021 |
| Completion of administrative activities and registration on ARTG | 2 December 2021 |
| Number of working days from submission dossier acceptance to registration decision* | 205 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Original publication date
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
Capsule
Strength
10 mg and 25 mg
Other ingredients
Tocofersolan, hypromellose, carrageenan, potassium chloride, titanium dioxide, carnauba wax, shellac and purified water (for both 10 mg and 25 mg capsules).
Iron oxide black, propylene glycol, strong ammonia solution (for 10 mg capsule only).
Indigo carmine, iron oxide yellow, iron oxide red, indigo carmine aluminium lake, glyceryl monooleate, and/or maize starch (for 25 mg capsule only).
Containers
Bottle
Pack sizes
60
Routes of administration
Oral
Dosage
The recommended dosage of Koselugo is 25 mg/m2 orally twice daily (approximately every 12 hours) until disease progression or unacceptable toxicity. Dosage is based on body surface area (BSA) of the patient.
Therapy should be initiated by a physician experienced in the diagnosis and the treatment of patients with neurofibromatosis type 1 (NF1) related tumours.
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
Koselugo was approved for the following therapeutic use:
Koselugo is indicated for the treatment of paediatric patients aged 2 years and above, with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).
What is this medicine and how does it work
Selumetinib is an orally available, inhibitor of mitogen activated protein kinase kinases 1 and 2 (MEK1/2) that is not competitive with respect to adenosine triphosphate (ATP). MEK1/2 proteins are critical components of the reticular activating system (RAS)-regulated rapidly accelerated fibrosarcoma (RAF)-mitogen activated protein kinase (MEK)-extracellular signal regulated kinases (ERK) pathway, which is often activated in different types of cancers. Selumetinib blocks MEK activity and inhibits growth of RAF-MEK-ERK pathway activated cell lines. Therefore, MEK inhibition can block the proliferation and survival of tumour cells in which the RAF-MEK-ERK pathway is activated.
What post-market commitments will the sponsor undertake
- Koselugo (selumetinib) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Koselugo 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 Koselugo European Union (EU)-risk management plan (RMP) (version 1 (succession 4), dated 6 May 2021, data lock point 3 September 2019), with Australian specific annex (version 1 (succession 3) , dated 25 August 2021), included with Submission PM 2020 05290-1-4 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).
Reports are to be provided in line with the current published list of EU 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 (rev 1), part VII.B structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration.
- Evaluation of long term safety effects and any potential for serious adverse risks of selumetinib on the growth and development of paediatric patients. Submission of complete final report and long term follow-up data from paediatric patients enrolled on SPRINT and ongoing or completed studies of selumetinib.
- Evaluate the long term safety effects and any potential for specific serious adverse risks of selumetinib in paediatric patients. Submission of complete final report and long term follow up safety data (minimum of 7 years) from paediatric patients enrolled on SPRINT and all ongoing or completed studies of selumetinib to include an analysis of the following toxicities in paediatric patients: ocular toxicity, cardiac toxicity, muscle toxicity, serious gastrointestinal toxicity, and serious dermatologic toxicity.
- Submit the final report and datasets from a pharmacokinetic (PK) trial in paediatric patients to confirm the effect of a low fat meal on selumetinib exposure with the marketed capsule formulation. Evaluate whether administration of selumetinib with food may alleviate gastrointestinal toxicities. Confirm appropriate dosing recommendation of selumetinib with a low fat meal that maintains efficacy with acceptable safety.