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Device/Product name
Inqovi 35/100
Active Ingredient
Decitabine and cedazuridine
Date of decision
Submission type
New chemical entity, New fixed dose combination
ATC codes
Decitabine: L01BC08, cedazuridine: not yet assigned
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 Inqovi 35/100 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, Health Canada (HC) 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) 9 January 2020
Submission dossier accepted and first round evaluation commenced 2 March 2020
First round evaluation completed 31 July 2020
Sponsor provides responses on questions raised in first round evaluation 30 September 2020
Second round evaluation completed 28 October 2020
Delegate's overall benefit-risk assessment and request for Advisory Committee advice 19 October 2020
Sponsor's pre-Advisory Committee response Not applicable
Advisory Committee meeting Not applicable
Registration decision (Outcome) 29 October 2020
Completion of administrative activities and registration on ARTG 2 November 2020
Number of working days from submission dossier acceptance to registration decision* 123

*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
Tablet, film coated
35 mg decitabine and 100 mg cedazuridine
Other ingredients
Lactose monohydrate, hypromellose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate and 85F15458 red
Pack sizes
Routes of administration

Prior to initiation of Inqovi 35/100, conduct baseline laboratory testing including complete blood cell counts with platelets, serum hepatic panel, and serum creatinine. Obtain complete blood cell counts prior to start of each cycle.

The recommended dose of Inqovi 35/100 is 1 tablet containing 35 mg of decitabine and 100 mg of cedazuridine taken orally once daily on Day 1 through 5 of each 28-day cycle for a minimum of 4 cycles. Best response may take longer than 4 cycles. Continue treatment as long as the patient continues to benefit. Repeat cycles every 28 days in the absence of haematologic toxicities not attributed to active disease and blood counts show absolute neutrophil count at least 1000/μL and platelets at least 50000/μL, or at least return to pretreatment levels. Delay or reduce the dose per cycle for haematologic toxicity.

For further information refer to the Product Information.

Pregnancy category
XDrugs which have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy.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

Inqovi 35/100 (decitabine and cedazuridine) was approved for the following therapeutic use:

Inqovi 35/100 is indicated for the treatment of adult patients with myelodysplastic syndromes (MDS) intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups, and patients with chronic myelomonocytic leukaemia (CMML).
What is this medicine and how does it work
Decitabine is a nucleoside metabolic inhibitor that is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into deoxyribonucleic acid (DNA) and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation and/or apoptosis. Decitabine inhibits DNA methylation in vitro, which is achieved at concentrations that do not cause major suppression of DNA synthesis. Decitabine induced hypomethylation in neoplastic cells may restore normal function to genes that are critical for the control of cellular differentiation, proliferation, and the immune system. In rapidly dividing cells, the cytotoxicity of decitabine may also be attributed to the formation of covalent adducts between DNA methyltransferase and decitabine incorporated into DNA. Non-proliferating cells are relatively insensitive to decitabine.Decitabine has been shown to induce hypomethylation both in vitro and in vivo. At the recommended Inqovi 35/100 dose, maximal or near maximal pharmacodynamic effect of long interspersed nucleotide elements-1 (LINE-1) demethylation was observed over the range of decitabine systemic exposures based on modelling.Cedazuridine inhibits cytidine deaminase (CDA). CDA is an enzyme that is responsible for the degradation of nucleosides, including decitabine. High levels of CDA in the gastrointestinal tract and liver rapidly degrade these nucleosides and prohibit or limit their oral bioavailability. Oral administration of cedazuridine with decitabine enhances the oral bioavailability of decitabine via inhibition of first pass metabolism of decitabine in the gut and liver by CDA.
What post-market commitments will the sponsor undertake
  • Inqovi 35/100 (decitabine 35 mg and 100 mg cedazuridine) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Inqovi 35/100 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 Inqovi 35/100 core management plan (risk management plan) (version 1.1, dated 25 August 2020, data lock point 19 March 2019), with Australian Specific Annex (ASA) (version 1.1, dated September 2020), included with submission PM-2020-00088-1-6, 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).

    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. 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.

    If the product is approved in the European Union (EU) during the three years period, reports can be provided in line with the published list of EU reference dates 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.

    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.

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