You are here
The Australian Prescription Medicine Decision Summary provides a short overview of the TGA's evaluation process leading to the registration of a new prescription medicine on the Australian Register of Therapeutic Goods (ARTG).
More in-depth information about the evaluation will be available in the Australian Public Assessment Report (AusPAR) for a particular prescription medicine, which can be found on the AusPAR search page once published.
Australian prescription medicine decision summary
|Submission type|| |
New biological entity
|Product name|| |
|Active ingredients|| |
|ATC codes|| |
|Date of decision|| |
8 October 2019
|Date of entry onto ARTG|| |
17 October 2019
|ARTG numbers|| |
|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.
Alexion Pharmaceuticals Australasia Pty Ltd
|Sponsor address|| |
20 Rodborough Road, Frenchs Forest NSW 2086
|Dose forms|| |
Injection, intravenous solution
|Other ingredients|| |
Monobasic sodium phosphate, dibasic sodium phosphate, sodium chloride, polysorbate 80, water for injections
|Pack sizes|| |
|Routes of administration|| |
The recommended dosing regimen for adult patients (≥ 18 years of age) with paroxysmal nocturnal haemoglobinuria (PNH) consists of a loading dose followed by maintenance dosing, administered by intravenous infusion. The doses to be administered are based on the patient's body weight. Maintenance doses should be administered at a once every 8 week interval, starting 2 weeks after loading dose administration.
For further information refer to the Product Information.
|Pregnancy category|| |
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 are inadequate or may be lacking, but available data show no 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.
Ultomiris (ravulizumab rch) was approved for the following therapeutic use:
Ultomiris is indicated for the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH).
Ravulizumab rch is a humanised monoclonal antibody (mAb) consisting of 2 identical 448 amino acid heavy chains and 2 identical 214 amino acid light chains and has a molecular weight of approximately 148kDa.
Ravulizumab rch is a terminal complement inhibitor that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a (the pro-inflammatory anaphylatoxin) and C5b (the initiating subunit of the terminal complement complex [C5b-9, also known as the membrane attack complex (MAC)]) and preventing the generation of the C5b-9 or MAC. By binding specifically to C5, ravulizumab rch antagonises terminal complement-mediated inflammation, cell activation, and cell lysis while preserving the early components of complement activation that are essential for opsonisation of microorganisms and clearance of immune complexes.
This mechanism of action provides the therapeutic rationale for the use of Ultomiris in paroxysmal nocturnal haemoglobinuria (PNH), in which uncontrolled complement activation is involved. In patients with PNH, complement mediated intravascular haemolysis is blocked with Ultomiris treatment.
Ravulizumab rch was specifically engineered to dissociate from C5 and associate with human neonatal Fc receptor (FcRn) at pH 6.0 (while minimising the impact in binding to C5 in intravascular space where the normal pH is 7.4). As a result, dissociation of antibody:C5 complexes in the acidified environment of the early endosome after pinocytosis is increased. Therefore, free antibody is recycled from the early endosome back into the vascular compartment by FcRn, resulting in an extended ravulizumab rch terminal elimination half-life.
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 Ultomiris was considered favourable for the therapeutic use approved.
The following table summarises the key steps and dates for this application.
|Submission dossier accepted and first round evaluation commenced||2 January 2019|
|First round evaluation completed||31 May 2019|
|Sponsor provides responses on questions raised in first round evaluation||27 June 2019|
|Second round evaluation completed||21 August 2019|
|Delegate's overall benefit-risk assessment and request for Advisory Committee advice||23 September 2019|
|Sponsor's pre-Advisory Committee response||N/A|
|Advisory Committee meeting||N/A|
|Registration decision (Outcome)||8 October 2019|
|Completion of administrative activities and registration on ARTG||17 October 2019|
|Number of working days from submission dossier acceptance to registration decision*||180|
*Statutory timeframe for standard applications is 255 working days
- Ultomiris (ravulizumab rch) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Ultomiris 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 Ultomiris European Union (EU)-Risk Management Plan (RMP) (version 1.4, dated 8 March 2018; DLP 2 May 2019), with Australian Specific Annex (version 2.0, dated 21 June 2019), included with submission PM-2018-05023-1-6, to be revised to the satisfaction of 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 this 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.
- For all injectable products the Product Information must be included with the product as a package insert.