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Relfydess (relabotulinumtoxinA, purified Botulinum toxin type A)
Australian Prescription Medicine Decision Summary
Sponsor
Device/Product name
Relfydess
Active Ingredient
relabotulinumtoxinA, purified Botulinum toxin type A
Published
Submission type
Type A (New chemical entity)
ATC codes
M03AX Other muscle relaxants, peripherally acting agents
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 by the sponsor.
The Relfydess clinical development program for moderate-to-severe GL and LCL included 6 studies:
- a Phase I dose-ranging study with GL and LCL treatment
- a Phase II dose-ranging study with GL treatment
- 3 pivotal Phase III double-blind, placebo-controlled studies (1 with GL only treatment, 1 with LCL only treatment, 1 with treatment in both GL and LCL regions), and
- a long-term, open-label safety study with multiple treatments in the GL and LCL regions.
The Relfydess clinical development program for moderate-to-severe GL and LCL included 6 studies:
- a Phase I dose-ranging study with GL and LCL treatment
- a Phase II dose-ranging study with GL treatment
- 3 pivotal Phase III double-blind, placebo-controlled studies (1 with GL only treatment, 1 with LCL only treatment, 1 with treatment in both GL and LCL regions), and
- a long-term, open-label safety study with multiple treatments in the GL and LCL regions.
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 March 2023 |
| Evaluation completed | 28 March 2024 |
| Delegate’s1 Overall benefit-risk assessment. | 13 May 2024 |
| Registration decision (Outcome) | 7 June 2024 |
| Administrative activities and registration in the ARTG completed | 1 July 2024 |
| Number of working days from submission dossier acceptance to registration decision2 | 390 |
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
Relfydess is to be included in the Black Triangle Scheme. The PI and CMI for Relfydess 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 with this medicine.
Dose forms
Clear, colourless to pale yellow solution
Strength
Relfydess contains 150 units in 1.5 mL of solution for injection
Other ingredients
- dibasic sodium phosphate dihydrate
- monobasic sodium phosphate
- dihydrate, potassium chloride
- sodium chloride
- polysorbate 80
- tryptophan
- water for injections.
Containers
Relfydess is supplied in 2 mL Type I glass vial, bromobutyl stopper and aluminium overseal with polypropylene flip-off top.
Pack sizes
1 or 10 vials of Relfydess 100 units/mL solution for injection.
Routes of administration
Intramuscular injection
Dosage
Glabellar Lines (GL):
Total recommended dose 50 units/0.5 mL.
Dose per injection: 5 injections of 10 units/0.1 mL: 2 injections on each side at the corrugator muscle and 1 injection at the procerus muscle near the nasofrontal angle.
Lateral Canthal Lines (LCL):
Total recommended dose 60 units/0.6 mL.
6 injections of 10 units/0.1 mL: 3 injections on each side at the orbicularis oculi muscle.
Combined treatment of Glabellar Lines and Lateral Canthal Lines:
Total recommended dose 110 units/1.1 mL.
11 injections total of 10 units/0.1 mL for combined GL and LCL.
Pregnancy category
B3
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 shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
There are only limited data from the use of botulinum toxin type A in pregnant women. RELFYDESS is not recommended during pregnancy and in women of childbearing potential not using contraception.
No reproductive and developmental toxicity studies have been performed with relabotulinumtoxinA. However, adverse embryofetal development effects have been seen in rat and rabbit studies with other botulinum toxins (lower fetal weights, delayed ossification, abortions and embryofetal development lethality). These adverse embryofetal development effects occurred in the context of maternotoxicity. The potential risk for humans is unknown.
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 shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
There are only limited data from the use of botulinum toxin type A in pregnant women. RELFYDESS is not recommended during pregnancy and in women of childbearing potential not using contraception.
No reproductive and developmental toxicity studies have been performed with relabotulinumtoxinA. However, adverse embryofetal development effects have been seen in rat and rabbit studies with other botulinum toxins (lower fetal weights, delayed ossification, abortions and embryofetal development lethality). These adverse embryofetal development effects occurred in the context of maternotoxicity. The potential risk for humans is unknown.
What was approved
Relfydess (relabotulinumtoxinA, purified Botulinum toxin type A) has been approved for the temporary improvement in the appearance of moderate to severe glabellar lines at maximum frown and moderate to severe lateral canthal lines seen at maximum smile.
What is this medicine and how does it work
Both glabellar lines ("frown lines") and lateral canthal lines ("crows feet") are caused by repeated contractions in the muscles surrounding these regions which over time may result in permanent wrinkles. Relfydess (Clostridium botulinum type A neurotoxin) prevents the release of the neurotransmitter acetylcholine from nerve cells. When injected intramuscularly, acetylcholine inhibition by Relfydess induces partial paralysis of the affected muscle. This temporarily reduces muscle activity, leading to the transient reduction of glabellar lines or lateral canthal lines. Botulinum toxin type A products have a long duration of action, measured in weeks to months.
What post-market commitments will the sponsor undertake
Relfydess is to be included in the Black Triangle Scheme. The PI and CMI for Relfydess must include the black triangle symbol for five years, or the product’s entire period of provisional registration, whichever is longer. The Black Triangle Scheme identifies new prescription medicines with a black triangle on the medicine information documents. The scheme also applies to prescription medicines being used in new ways, such as a medicine that is now being used for children. The black triangle is a visual reminder to encourage health practitioners and patients to report a problem or side effect.
The Relfydess Core-Risk Management Plan (RMP) (version 1.0, dated 14 December 2022, data lock point 20 July 2022), with Australian Specific Annex (version 2.0, dated 15 November 2023), included with submission. PM-2023-00708-1-1, 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).
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 the AusPAR dataset.
The latest news and updates regarding therapeutic goods regulation can be found on the news page.