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Korsuva
Sponsor
Device/Product name
Korsuva
Active Ingredient
difelikefalin acetate
Date of decision
Published
Submission type
New chemical entity
ATC codes
V03AX04
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 Korsuva 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 application was evaluated as part of the Australia-Canada-Singapore-Switzerland- United Kingdom (Access) Consortium, with work-sharing between TGA, Health Canada, Health Sciences Authority Singapore and Swissmedic. Each regulator made independent decisions regarding approval (market authorisation) of the new medicine.
| Description | Date |
|---|---|
| Submission dossier accepted and first round evaluation commenced | 21 October 2021 |
| First round evaluation completed | 22 February 2022 |
| Sponsor provides responses on questions raised in first round evaluation | 17 June 2022 |
| Second round evaluation completed | 20 July 2022 |
| Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice | 8 July 2022 |
| Sponsor’s pre-Advisory Committee response | 22 July 2022 |
| Advisory Committee meeting | 4 and 5 August 2022 |
| Registration decision (Outcome) | 9 November 2022 |
| Completion of administrative activities and registration on ARTG | 10 November 2022 |
| Number of working days from submission dossier acceptance to registration decision* | 211 |
* 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
Solution for injection
Strength
50 µg/1 mL
Other ingredients
Acetic acid, sodium acetate trihydrate, sodium chloride, and water for injections
Containers
Vial
Pack sizes
3 and 12
Routes of administration
Intravenous
Dosage
The recommended dose of Korsuva is 0.5 µg/kg dry body weight (that is the target postdialysis weight) by intravenous bolus injection three times per week. The total dose volume (mL) required from the vial should be calculated as follows: 0.01 x prescription dry body weight (kg), rounded to the nearest tenth (0.1 mL).
For further information refer to the Product Information.
Pregnancy category
B1
Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed.
Studies in animals have not shown evidence of an increased occurrence of fetal damage.
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 been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed.
Studies in animals have not shown evidence of an increased occurrence of fetal damage.
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
Korsuva (difelikefalin acetate) was approved for the following therapeutic use:
Korsuva is indicated for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adult patients on haemodialysis.
What is this medicine and how does it work
Difelikefalin is a selective kappa opioid receptor agonist with low central nervous system penetration.
The physicochemical properties of difelikefalin (hydrophilic, synthetic D-amino acid peptide with high polar surface area and charge at physiological potential of hydrogen (pH)) minimise its passive diffusion (permeability) and active transport across membranes, thus limiting penetration into the central nervous system.
The pathophysiology of chronic kidney disease associated pruritus is thought to be multifactorial, including systemic inflammation and an imbalance in the endogenous opioid system (for example, overexpression of mu opioid receptors and concomitant downregulation of kappa opioid receptors).
Opioid receptors are known to modulate itch signals and inflammation, with kappa opioid receptor activation reducing itch and producing immunomodulatory effects.
The activation of kappa opioid receptors on peripheral sensory neurons and immune cells by difelikefalin are considered mechanistically responsible for the antipruritic and anti-inflammatory effects.
Abuse and dependence potential has been examined in rat studies, which do not indicate likely potential for physical dependence or abuse in rats.
The physicochemical properties of difelikefalin (hydrophilic, synthetic D-amino acid peptide with high polar surface area and charge at physiological potential of hydrogen (pH)) minimise its passive diffusion (permeability) and active transport across membranes, thus limiting penetration into the central nervous system.
The pathophysiology of chronic kidney disease associated pruritus is thought to be multifactorial, including systemic inflammation and an imbalance in the endogenous opioid system (for example, overexpression of mu opioid receptors and concomitant downregulation of kappa opioid receptors).
Opioid receptors are known to modulate itch signals and inflammation, with kappa opioid receptor activation reducing itch and producing immunomodulatory effects.
The activation of kappa opioid receptors on peripheral sensory neurons and immune cells by difelikefalin are considered mechanistically responsible for the antipruritic and anti-inflammatory effects.
Abuse and dependence potential has been examined in rat studies, which do not indicate likely potential for physical dependence or abuse in rats.
What post-market commitments will the sponsor undertake
- Korsuva (difelikfalin) is to be included in the Black Triangle Scheme. The PI [Product Information] and CMI [Consumer Medicine Information] for Korsuva 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 Korsuva EU [European Union]-risk management plan (RMP) (version 1.5, dated 8 March 2022, data lock point 15 May 2020), with Australia specific annex (version 1.0, dated 17 June 2022), included with Submission PM-2021-04071-1-1, 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.
- For all injectable products the Product Information must be included with the product as a package insert.