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Isturisa
ARTGs
Device/Product name
Isturisa
Active Ingredient
Osilodrostat phosphate
Date of decision
Published
Submission type
New chemical entity
ATC codes
H02CA02
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 Isturisa 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 comparable overseas regulator approach B (COR-B) application.
| Description | Date |
|---|---|
| Designation (Orphan) | 29 April 2021 |
| Submission dossier accepted and first round evaluation commenced | 2 August 2021 |
| First round evaluation completed | 6 December 2021 |
| Sponsor provides responses on questions raised in first round evaluation | 9 February 2022 |
| Second round evaluation completed | 11 April 2022 |
| Delegate's overall benefit-risk assessment | 21 April 2022 |
| Sponsor's pre-Advisory Committee response | Not Applicable |
| Advisory Committee meeting | Not Applicable |
| Registration decision (Outcome) | 6 May 2022 |
| Completion of administrative activities and registration on ARTG | 12 May 2022 |
| Number of working days from submission dossier acceptance to registration decision* | 122 |
*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
Film coated tablet
Strength
1 mg, 5 mg and 10 mg
Other ingredients
Colloidal anhydrous silica, croscarmellose sodium, hypromellose, macrogol 4000, magnesium stearate, mannitol, microcrystalline cellulose, purified talc, titanium dioxide, iron oxide yellow, iron oxide red (1 mg and 10 mg), iron oxide black (10 mg)
Containers
Blister pack
Pack sizes
60
Routes of administration
Oral
Dosage
The recommended starting dose is 2 mg osilodrostat twice daily. For patients of Asian ancestry, a reduced starting dose of 1 mg twice daily is recommended (see section 5.2 Pharmacokinetic Properties).
The dose can be gradually titrated (initially by dose increments of 1 or 2 mg) based on individual response and tolerability, with the aim to achieve normal cortisol levels.
The maximum recommended dose of Isturisa is 30 mg twice daily.
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
Isturisa (osilodrostat) was approved for the following therapeutic use:
Isturisa is indicated for the treatment of endogenous Cushing’s syndrome in adults.
What is this medicine and how does it work
Osilodrostat is a cortisol synthesis inhibitor. It inhibits 11β hydroxylase (CYP11B1), the enzyme responsible for the final step of cortisol biosynthesis in the adrenal gland.
CYP11B1 inhibition is associated with the accumulation of precursors such as 11 deoxycortisol and acceleration of adrenal biosynthesis including androgens. In Cushing’s disease, the fall in plasma cortisol concentration also stimulates adrenocorticotropic hormone (ACTH) secretion, via the feedback mechanism which accelerates steroid biosynthesis (see section 4.8 Adverse effects (undesirable effects).
CYP11B1 inhibition is associated with the accumulation of precursors such as 11 deoxycortisol and acceleration of adrenal biosynthesis including androgens. In Cushing’s disease, the fall in plasma cortisol concentration also stimulates adrenocorticotropic hormone (ACTH) secretion, via the feedback mechanism which accelerates steroid biosynthesis (see section 4.8 Adverse effects (undesirable effects).
What post-market commitments will the sponsor undertake
- Osilodrostat (Isturisa) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicine Information (CMI) for Isturisa 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 Isturisa European Union (EU)-risk management plan (RMP) (version 1.2, dated 25 November 2021, data lock point 8 July 2021), with Australian specific annex (version 1.3, dated 9 March 2022), included with Submission PM 2021 02641 1 5, 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 (revision 1), Part VII.B structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration.
- The sponsor should submit the data from PASS study when available. This should be submitted as a new application.