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Letybo
Sponsor
ARTGs
Device/Product name
Letybo
Active Ingredient
LetibotulinumtoxinA
Date of decision
Published
Submission type
New chemical entity
ATC codes
M03AX01
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 Letybo 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.
|
Description |
Date |
|---|---|
|
Submission dossier accepted and first round evaluation commenced |
2 August 2021 |
|
First round evaluation completed |
4 January 2022 |
|
Sponsor provides responses on questions raised in first round evaluation |
4 March 2022 |
|
Second round evaluation completed |
1 August 2022 |
|
Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice |
6 September 2022 |
|
Sponsor’s pre-Advisory Committee response |
15 September 2022 |
|
Advisory Committee meeting |
6 October 2022 |
|
Registration decision (Outcome) |
23 November 2022 |
|
Completion of administrative activities and registration on ARTG |
28 November 2022 |
|
Number of working days from submission dossier acceptance to registration decision* |
222 |
*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
Powder for injection
Strength
50 and 100 units
Other ingredients
Albumin and sodium chloride
Containers
Vial
Pack sizes
One vial
Routes of administration
Intramuscular injection
Dosage
Letybo should only be administered by medical practitioners with suitable qualifications and proven experience in the application of botulinum toxin and in the use of the necessary equipment.
The optimum dose and number of injection sites in the treated muscles should be individualised for each patient and determined by the treating doctor.
The dose per injection site is 4 units into each of the five injection sites, two injections in each corrugator muscle and one injection in the procerus muscle. The standard dose is 20 units.
For further information refer to the Product Information.
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.
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 shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
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
Letybo (letibotulinumtoxinA) was approved for the following therapeutic use:
Letybo is indicated for the temporary improvement in the appearance of moderate to severe glabellar frown lines in adults.
What is this medicine and how does it work
LetibotulinumtoxinA blocks cholinergic transmission at the neuromuscular junction by inhibiting the release of acetylcholine from peripheral cholinergic nerve terminals. This inhibition occurs according to the following sequence:
- heavy chain of toxin binding to cholinergic nerve terminals
- internalisation of the toxin within vesicles into the nerve terminal
- translocation of the light-chain of the toxin molecule into the cytosol of the nerve terminal
- enzymatic cleavage of SNAP25, the presynaptic target protein essential for the release of acetylcholine.
Complete recovery of endplate function/impulse transmission after intramuscular injection normally occurs within three to four months as nerve terminals sprout and reconnect with the muscle endplate and the presynaptic neurotransmitter release mechanism becomes functional again.
- heavy chain of toxin binding to cholinergic nerve terminals
- internalisation of the toxin within vesicles into the nerve terminal
- translocation of the light-chain of the toxin molecule into the cytosol of the nerve terminal
- enzymatic cleavage of SNAP25, the presynaptic target protein essential for the release of acetylcholine.
Complete recovery of endplate function/impulse transmission after intramuscular injection normally occurs within three to four months as nerve terminals sprout and reconnect with the muscle endplate and the presynaptic neurotransmitter release mechanism becomes functional again.
What post-market commitments will the sponsor undertake
- Letybo (letibotulinumtoxinA) is to be included in the Black Triangle Scheme. The PI [product information] and CMI [Consumer Medicines Information] for Letybo 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 letibotulinumtoxinA (Letybo) AU-Risk Management Plan (RMP) (version 0.2, dated 20 February 2022, data lock point 1 September 2020), included with submission PM‑2021‑02698-1-1, 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).
Unless agreed separately between the supplier who is the recipient of the approval and the TGA, the first report must be submitted to TGA no later than 15 calendar months after the date of the approval letter. The subsequent reports must be submitted no less frequently than annually from the date of the first submitted report until the period covered by such reports is not less than three years from the date of the approval letter. The annual submission may be made up of two PSURs each covering six months. If the sponsor wishes, the six monthly reports may be submitted separately as they become available.
If the product is approved in the EU [European Union] during the three years period, reports can be provided in line with the published list of EU reference dates no less frequently than annually from the date of the first submitted report 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 (Rev 1), Part VII.B Structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration. Each report must have been prepared within ninety calendar days of the data lock point for that report.
- GMP [Good Manufacturing Practice] clearance for listed manufacturers: All GMP clearances must be approved prior to registration and supply of product to Australia. A commitment is required from the sponsor that they maintain the validity of all manufacturer GMP clearances for the duration of product supply to Australia. Additionally, that adherence to the conditions of GMP clearance approval is upheld.
All batches of Letybo supplied in Australia must comply with the product details and specifications approved during evaluation and detailed in the Certified Product Details (CPD).
When requested by the TGA, the sponsor should be prepared to provide product samples, specified reference materials and documentary evidence to enable the TGA to conduct laboratory testing on the product. Outcomes of laboratory testing are published biannually in the TGA Database of Laboratory Testing Results http://www.tga.gov.au/ws-labs index and periodically in testing reports on the TGA website.
- For all injectable products the Product Information must be included with the product as a package insert.