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Nextstellis
ARTGs
Device/Product name
Nextstellis
Active Ingredient
Estetrol monohydrate/drospirenone
Date of decision
Published
Submission type
New chemical entity
ATC codes
G03AA18
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 Nextstellis 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 September 2020 |
| First round evaluation completed | 6 May 2021 |
| Sponsor provides responses on questions raised in first round evaluation | 1 June 2021 |
| Second round evaluation completed | 16 June 2021 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 30 August 2021 |
| Sponsor's pre-Advisory Committee response | 14 September 2021 |
| Advisory Committee meeting | 30 September and 1 October 2021 |
| Registration decision (Outcome) | 10 November 2021 |
| Completion of administrative activities and registration on ARTG | 26 November 2021 |
| Number of working days from submission dossier acceptance to registration decision* | 200 |
*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
14.2 mg estetrol and 3 mg drospirenone
Other ingredients
Lactose monohydrate, maize starch, magnesium stearate, hypromellose, hyprolose, purified talc, hydrogenated cottonseed oil, titanium dioxide (for both the active and inactive tablets)
Sodium starch glycollate type A, povidone and iron oxide red (for the active tablet only)
Containers
Blister pack
Pack sizes
1 x 28 tablets (24 active and 4 placebo tablets)3 x 28 tablets (72 active and 12 placebo tablets)6 x 28 tablets (144 active and 24 placebo tablets)
Routes of administration
Oral
Dosage
Nextstellis should be started using instructions for starting or switching (under Section 4.2 Dose and method of administration of the Product Information). Women with no current use of hormonal contraception should consider the possibility of pregnancy prior to initiation of this product.
Nextstellis (pink active and white inactive tablets) is swallowed whole once a day. Take one tablet daily for 28 consecutive days. Once established on Nextstellis, the administration cycle will involve 24 active pink tablets taken consecutively followed by 4 inactive white tablets. This may be across different blister packs. Tablets must be taken every day at about the same time of the day so that the interval between consecutive tablets is the same.
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
Nextstellis (estetrol (as monohydrate)/drospirenone) was approved for the following therapeutic use:
Nextstellis is indicated for use by women of reproductive potential to prevent pregnancy.
What is this medicine and how does it work
Combined oral contraceptives (COCs) prevent pregnancy primarily by suppressing ovulation. Estetrol (E4) is a naturally occurring estrogen produced by the human fetal liver. It is only produced during human pregnancy and reaches the maternal circulation through the placenta. The E4 in Nextstellis is synthesised from a plant source. Estetrol displays a high selectivity for estrogen receptors (ERs) and binds to both estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), with a 4 to 6 times higher affinity for ERα compared to ERβ. Estrogen agonist activity by E4 was demonstrated in various cell based assays in vitro and animal models in vivo. Estetrol differs from ethinylestradiol by the lack of an ethinyl group in the 17-alpha position. In humans, E4 is an end product of steroid metabolism and is not reconverted to estriol, estradiol or estrone.The progestin drospirenone possesses antigonadotropic, antiandrogenic and mild antimineralocorticoid properties and has no estrogenic, glucocorticoid or antiglucocorticoid activity. These properties are pharmacologically similar to the natural hormone progesterone.
What post-market commitments will the sponsor undertake
- Nextstellis (estetrol monohydrate/drospirenone) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Nextstellis 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 Nextstellis European Union (EU)-risk management plan (RMP) (version 0.7, dated 17 March 2021, data lock point 31 October 2019), with Australian specific annex (version 0.2, dated 28 April 2021), included with Submission PM-2020-04185-1-5, 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).
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 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.