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Dayvigo
Sponsor
ARTGs
338631 and 338645
338631 and 338645
Device/Product name
Dayvigo
Active Ingredient
Lemborexant
Date of decision
Published
Submission type
New chemical entity
ATC codes
Not yet assigned
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 Dayvigo 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 | 30 June 2020 |
| First round evaluation completed | 1 December 2020 |
| Sponsor provides responses on questions raised in first round evaluation | 29 January 2021 |
| Second round evaluation completed | 5 March 2021 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 6 May 2021 |
| Sponsor's pre-Advisory Committee response | 21 May 2021 |
| Advisory Committee meeting | 3 and 4 June 2021 |
| Registration decision (Outcome) | 15 July 2021 |
| Completion of administrative activities and registration on ARTG | 16 July 2021 |
| Number of working days from submission dossier acceptance to registration decision* | 224 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Original publication date
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
Film coated tablet
Strength
5 mg and 10 mg
Other ingredients
lactose monohydrate, hyprolose, magnesium stearate, Opadry complete film coating system 03F42222 (for 5 mg tablets) and Opadry complete film coating system 03F43101 (for 10 mg tablets)
Containers
Blister pack
Pack sizes
28 and 3 (3 tablets pack is for sample only) (5 mg tablets)28 (10 mg tablets)
Routes of administration
Oral
Dosage
The recommended dose of Dayvigo is 5 mg, taken no more than once per night and within a few minutes before going to bed, with at least 7 hours remaining before the planned time of awakening. If the 5 mg dose is well tolerated but greater effect is needed, the dose can be increased to 10 mg once daily, the maximum recommended dose. Dayvigo should be used at the lowest dose and for the shortest duration as clinically indicated.
For further information refer to the Product Information.
Pregnancy category
B3Drugs 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
Dayvigo (lemborexant) was approved for the following therapeutic use:
Dayvigo is indicated for the treatment of insomnia, characterised by difficulties with sleep onset and/or sleep maintenance in accordance with latest DSM criteria
What is this medicine and how does it work
Lemborexant is a competitive antagonist of both orexin receptors, orexin receptors type 1 (OX1R) and orexin receptors type 2 (OX2R), with a higher affinity for OX2R. It belongs to the pharmacologic class of orexin receptor antagonists. The orexin neuropeptide signalling system is a central promoter of wakefulness. Blocking the binding of wake promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive.Antagonism or orexin receptors may also underlie potential adverse effects such as signs of narcolepsy/cataplexy. Lemborexant administered to mice at oral doses greater than 10 mg/kg resulted in behaviour characteristic of cataplexy when presented with chocolate. Chocolate is a stimulus that has been demonstrated to increase cataplexy occurrences in narcoleptic mice.
What post-market commitments will the sponsor undertake
- Dayvigo (lemborexant) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Dayvigo 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 Dayvigo Canadian-risk management plan (RMP) (version 1.0, dated 25 August 2019, data lock point 11 January 2019), with Australian specific annex (version 2.0, dated 27 January 2021), included with submission PM-2020-02421-1-1, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.
An obligatory component of RMP 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 European Union (EU) 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.
- Submit the study report of in vitro drug-drug interaction (DDI) study to assess the potential of lemborexant as an inducer for cytochrome P450 family 2 subfamily C member 8 (CYP2C8), cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and cytochrome P450 family 2 subfamily C member 19 (CYP2C19).
- Submit the study report of in vitro DDI study to assess the potential of lemborexant as an P‑glycoprotein substrate at clinically relevant concentrations.