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Oxlumo (lumasiran)
Australian Prescription Medicine Decision Summary
Sponsor
Device/Product name
Oxlumo
Active Ingredient
lumasiran
Date of decision
Published
Submission type
Type A (New chemical entity)
ATC codes
A16AX(18) - Other alimentary tract and metabolism products
Decision
Approved
What was the decision based on
The approval was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology), clinical (pharmacology, safety and efficacy) and risk management plan data submitted to the TGA by the Sponsor.
The effectiveness and safety of Oxlumo was demonstrated in a Phase 1/2 study, an open-label extension study and three Phase 3 studies, including:
-a randomized, double-blind, placebo-controlled study in adults and children greater than 6 years of age with PH1
-a single-arm study in infants and children less than 6 years of age with PH1 and
-a single arm study in patients of all ages with advanced PH1 with or without dialysis.
The effectiveness and safety of Oxlumo was demonstrated in a Phase 1/2 study, an open-label extension study and three Phase 3 studies, including:
-a randomized, double-blind, placebo-controlled study in adults and children greater than 6 years of age with PH1
-a single-arm study in infants and children less than 6 years of age with PH1 and
-a single arm study in patients of all ages with advanced PH1 with or without dialysis.
What steps were involved in the decision process
The active ingredient with its proposed indication was given orphan drug designation and was evaluated under the Comparable Overseas Regulator B (COR-B) report-based process.
| Description | Date |
|---|---|
| Designation (Orphan) | 27 July 2023 |
| Submission dossier accepted and first round evaluation commenced | 3 October 2023 |
| Evaluation completed | 15 April 2024 |
| Delegate’s Overall benefit-risk assessment | 3 May 2024 |
| Registration decision (Outcome) | 20 June 2024 |
| Administrative activities and registration in the ARTG completed | 24 June 2024 |
| Number of working days from submission dossier acceptance to registration decision* | 182 days |
* The COR-B process has a 175 working day evaluation and decision timeframe.
Date of entry onto ARTG
Black triangle scheme
Oxlumo is to be included in the Black Triangle Scheme. The PI and CMI for Oxlumo 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.
Dose forms
Clear, colourless to yellow solution.
Strength
Each mL of solution contains lumasiran sodium equivalent to 189 mg lumasiran.
Each vial contains 0.5 mL of lumasiran sodium solution equivalent to 94.5 mg lumasiran.
Each vial contains 0.5 mL of lumasiran sodium solution equivalent to 94.5 mg lumasiran.
Other ingredients
Sodium hydroxide (pH adjustment)
Phosphoric acid (pH adjustment)
Water for injections
Containers
Glass vial with a fluoropolymer-coated rubber stopper and an aluminium overseal with a flip-off button. Each vial contains 0.5 mL solution for injection
Pack sizes
One vial per pack
Routes of administration
Subcutaneous injection
Dosage
The recommended dose of Oxlumo consists of loading doses given once a month for 3 doses, followed by maintenance doses beginning one month after the last loading dose. Dosing is dependent on body weight; see the Product Information document for dosing details.
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.
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.
What was approved
Oxlumo was approved for the treatment of primary hyperoxaluria type 1 (PH1) in all age groups.
What is this medicine and how does it work
Oxlumo (lumasiran) is a double-stranded small interfering ribonucleic acid (siRNA). Lumasiran reduces levels of glycolate oxidase (GO) enzyme by targeting the hydroxyacid oxidase 1 (HAO1) gene messenger ribonucleic acid (mRNA) in liver cells through siRNA-mediated RNA interference (a biochemical pathway in cells that can silence gene expression). Decreased GO enzyme levels reduce the amount of available glyoxylate, a chemical which liver cells use to produce oxalate. This results in the reduction of oxalate levels in the blood and urine. Excess oxalate is the cause of disease in patients with PH1 so reducing oxalate levels reduces disease symptoms.
PH1 is a genetic disease caused by a change in the AGXT (alanine-glyoxylate aminotransferase) gene. This gene is a set of instructions for synthesising the protein alanine-glyoxylate aminotransferase (AGT) which breaks down oxalate in the liver. People living with PH1 either make less AGT or don’t make it at all. Since GO activity occurs before AGT activity in this sequence of chemical reactions, the ability of lumasiran to reduce oxalate levels can proceed despite the presence of the altered AGXT gene.
PH1 is a genetic disease caused by a change in the AGXT (alanine-glyoxylate aminotransferase) gene. This gene is a set of instructions for synthesising the protein alanine-glyoxylate aminotransferase (AGT) which breaks down oxalate in the liver. People living with PH1 either make less AGT or don’t make it at all. Since GO activity occurs before AGT activity in this sequence of chemical reactions, the ability of lumasiran to reduce oxalate levels can proceed despite the presence of the altered AGXT gene.
What post-market commitments will the sponsor undertake
Oxlumo (lumasiran) is to be included in the Black Triangle Scheme. The black triangle is a visual reminder to encourage health practitioners and patients to report problems or side effects experienced with this medicine. The PI and CMI for Oxlumo must include the black triangle symbol and mandatory accompanying text for five years, which starts from the date of first supply of the product.
The OXLUMO Risk Management Plan (RMP) as agreed with the TGA will be implemented in Australia. An obligatory component of RMPs is routine pharmacovigilance, which includes the submission of periodic safety update reports.
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.