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Fabhalta (iptacopan)
Australian Prescription Medicine Decision Summary
Device/Product name
Fabhalta
Active Ingredient
Iptacopan
Date of decision
Published
Submission type
Type A - New chemical entity
ATC codes
L04AJ-08 (L04AJ = Complement inhibitors)
Decision
Approved
What was the decision based on
An extensive set of quality, nonclinical pharmacology, clinical pharmacology, pharmacokinetic and toxicology studies were performed with iptacopan to demonstrate the integrity of the drug product and the effectiveness and safety of iptacopan in paroxysmal nocturnal haemoglobinuria.
The key clinical trials which demonstrated the effectiveness and safety of iptacopan were:
• A pivotal phase III study: a randomised, active-controlled study, comparing iptacopan monotherapy to anti-C5 treatment (C5 is a complement component) in paroxysmal nocturnal haemoglobinuria patients with residual anaemia despite prior anti-C5 therapy.
• A supportive Phase III study: a single arm, open-label study, evaluating iptacopan monotherapy in PNH patients who were naïve to complement inhibitor treatment.
These studies (and others) demonstrated the persistence of efficacy (and feasibility for long-term use) of iptacopan for up to 3 years.
The key clinical trials which demonstrated the effectiveness and safety of iptacopan were:
• A pivotal phase III study: a randomised, active-controlled study, comparing iptacopan monotherapy to anti-C5 treatment (C5 is a complement component) in paroxysmal nocturnal haemoglobinuria patients with residual anaemia despite prior anti-C5 therapy.
• A supportive Phase III study: a single arm, open-label study, evaluating iptacopan monotherapy in PNH patients who were naïve to complement inhibitor treatment.
These studies (and others) demonstrated the persistence of efficacy (and feasibility for long-term use) of iptacopan for up to 3 years.
What steps were involved in the decision process
This submission was evaluated under the standard prescription medicines registration process.
| Description | Date |
|---|---|
| Submission dossier accepted and first round evaluation commenced | 31 July 2023 |
| Evaluation completed | 9 April 2024 |
| Delegate’s* Overall benefit-risk assessment and request for Advisory Committee advice | 12 April 2024 |
| Advisory Committee meeting | 19 July 2024 |
| Registration decision (Outcome) | 7 August 2024 |
| Registration in the ARTG | 12 August 2024 |
| Number of working days from submission dossier acceptance to registration decision# | 263 |
* The ‘Delegate’ is the Delegate of the Secretary of the Department of Health and Aged Care who made the final decision to either include the new medicine/indication on the ARTG or reject the submission, under section 25 of the Therapeutic Goods Act
# Statutory timeframe for standard submissions is 255 working days
Date of entry onto ARTG
Black triangle scheme
Fabhalta is to be included in the Black Triangle Scheme. The PI and CMI for Fabhalta must include the black triangle symbol ▼ for five years. The black triangle is a visual reminder to encourage health practitioners and patients to report a problem or side effect observed with this medicine.
Dose forms
Capsule
Strength
Each capsule contains 200 mg iptacopan (as 225.8 mg iptacopan hydrochloride monohydrate).
Other ingredients
Capsule shell: Hard gelatin, red iron oxide (E 172), titanium dioxide (E 171), and yellow iron oxide (E 172).
Printing ink: Black iron oxide (E 172), concentrated ammonia solution (E 527), propylene glycol (E 1520), potassium hydroxide (E 525), and shellac (E 904).
Containers
Pack of 56 hard capsules in blister packs backed with aluminium foil.
Pack sizes
One pack = 56 capsules
Routes of administration
Oral
Dosage
The recommended dose is 200 mg taken orally twice daily.
Pregnancy category
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.
There are insufficient data on Fabhalta use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with untreated PNH in pregnancy. Paroxysmal nocturnal haemoglobinuria in pregnancy is associated with adverse maternal outcomes, including worsening cytopenia, thrombotic events, infections, bleeding, miscarriages and increased maternal mortality, as well as adverse fetal outcomes, including fetal death and premature delivery. The use of Fabhalta in pregnant women or women planning to become pregnant may be considered following an assessment of the risks and benefits.
No malformations of other adverse effects on embryofetal development were observed in rats or rabbits with oral administration of iptacopan during the major period of organogenesis up to the highest doses tested (1000 mg/kg/day and 450 mg/kg/day in the respective species). These doses yield exposure to iptacopan 18-times higher in rats (based on unbound plasma AUC) and 8-times higher in rabbits (based on AUC for total drug) than in patients at the MRHD.
Studies in animals have not shown evidence of an increased occurrence of fetal damage.
There are insufficient data on Fabhalta use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with untreated PNH in pregnancy. Paroxysmal nocturnal haemoglobinuria in pregnancy is associated with adverse maternal outcomes, including worsening cytopenia, thrombotic events, infections, bleeding, miscarriages and increased maternal mortality, as well as adverse fetal outcomes, including fetal death and premature delivery. The use of Fabhalta in pregnant women or women planning to become pregnant may be considered following an assessment of the risks and benefits.
No malformations of other adverse effects on embryofetal development were observed in rats or rabbits with oral administration of iptacopan during the major period of organogenesis up to the highest doses tested (1000 mg/kg/day and 450 mg/kg/day in the respective species). These doses yield exposure to iptacopan 18-times higher in rats (based on unbound plasma AUC) and 8-times higher in rabbits (based on AUC for total drug) than in patients at the MRHD.
What was approved
Fabhalta (iptacopan) has been approved for the treatment of adult patients with paroxysmal nocturnal haemoglobinuria.
What is this medicine and how does it work
Iptacopan is a complement inhibitor. The complement system (or 'complement cascade') is a part of the immune system. It consists of inactive proteins in the blood which, upon receiving an appropriate trigger, initiate signals which result in activation of the complement cascade. This stimulates phagocytes (cells that engulf and kill microbes/microbe infected cells), to clear cellular debris, induce inflammation to attract other immune cells, and activate the 'membrane attack complex' which punches holes in the membranes of infected cells or microbes, facilitating their destruction. In paroxysmal nocturnal haemoglobinuria, red blood cell destruction within blood vessels is mediated by this membrane attack complex; other complement components induce destruction of red blood cells outside the blood vessels. Iptacopan selectively targets Factor B; Factor B activates red cell death within and outside blood vessels. Inhibition of Factor B by iptacopan, and therefore the complement pathways it activates, prevents red blood cell destruction. Complement inhibition is how iptacopan mediates its therapeutic effect of preventing red blood cell death. .
What post-market commitments will the sponsor undertake
Fabhalta is to be included in the Black Triangle Scheme. The PI and CMI for Fabhalta must include the black triangle symbol and mandatory accompanying text for five years. The Black Triangle Scheme identifies new prescription medicines with a black triangle on the medicine information documents. The black triangle is a visual reminder to encourage health practitioners and patients to report a problem or side effect associated with this medicine.
The Fabhalta EU-Risk Management Plan (RMP) ((version 1.1, dated 6 December 2023, data lock point 2 November 2022) with Australian Specific Annex (version 1.1, dated 22 February 2024), included with submission PM-2023-02564-1-6 and any subsequent revisions, as agreed with the TGA will be implemented in Australia. An obligatory component of risk management plans is routine pharmacovigilance which includes the submission of periodic safety update reports (PSURs).
An obligatory component of risk management plans is routine pharmacovigilance. Routine pharmacovigilance includes the submission of periodic safety update reports (PSURs).
More information
The latest Product Information (PI) and Consumer Medicine Information (CMI) can be found by searching the Australian Register of Therapeutic Goods (ARTG).
Australian Public Assessment Reports (AusPARs) can be found by searching our AusPAR dataset.
The latest news and updates regarding therapeutic goods regulation can be found on our news page.