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Sohonos
Sponsor
ARTGs
Device/Product name
Sohonos
Active Ingredient
Palovarotene
Date of decision
Published
Submission type
New chemical entity
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 Sohonos 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 |
|---|---|
Designation (Orphan) | 11 March 2021 18 August 2021 (extension) |
Submission dossier accepted and first round evaluation commenced | 30 September 2022
|
Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice | 5 September 2023 |
Advisory Committee meeting | 5 and 6 October 2023
|
Registration decision (Outcome) | 27 November 2023
|
Completion of administrative activities and registration on ARTG | 28 November 2023
|
Number of working days from submission dossier acceptance to registration decision* | 202
|
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Black triangle scheme
Yes
Dose forms
Hard capsule
Strength
1 mg, 1.5 mg, 2.5 mg, 5 mg and 10 mg
Containers
Blister pack
Pack sizes
28
Routes of administration
Oral
Dosage
Sohonos should only be prescribed under the supervision of specialist medical practitioners with expertise in managing fibrodysplasia ossificans progressiva.
Pregnancy testing and contraceptive measures must be followed prior to dosing Sohonos in females of childbearing potential. Precautions should be taken before handling or administering the medicinal product.
Recommended dose is based on multiple factors, including whether it is for chronic or flare-up treatment, the age and weight of the patient and whether the patient experiences adverse reactions that require dose reduction.
Pregnancy category
X
Drugs which have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy.
The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. The pregnancy database 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 such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy.
The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. The pregnancy database 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
Sohonos (palovarotene) was approved for the following therapeutic use:
Sohonos is indicated to reduce the formation of heterotopic ossification in adults and children aged 8 years and above for females and 10 years and above for males with fibrodysplasia ossificans progressiva (FOP).
What is this medicine and how does it work
Palovarotene is a retinoic acid receptor gamma (RARγ) selective agonist. Fibrodysplasia ossificans progressiva (FOP, formerly referred as myositis ossificans progressiva) is a genetic condition caused by a gain-of-function mutation in the gene encoding activin A receptor type 1 (also known as activin receptor-like kinase 2), a bone morphogenetic protein (BMP) expressed by chondrocytes and osteoblasts. The mutant protein aberrantly activates the Smad1/5/8 signalling pathway, diverting mesenchymal progenitor cells from a soft tissue fate (allowing for normal tissue repair) to an osseous fate (promoting chondrogenesis and heterotopic bone formation).
RARγ is expressed in chondrogenic cells and chondrocytes, where it operates as an unliganded transcriptional repressor. Activation of RARγ downregulates BMP signalling by reducing phosphorylation of downstream effectors Smad1/5/8. In this way, palovarotene prevents chondrogenesis and heterotopic ossification in FOP, and enables normal muscle tissue repair or regeneration to take place, reducing damage to muscle tissue.
RARγ is expressed in chondrogenic cells and chondrocytes, where it operates as an unliganded transcriptional repressor. Activation of RARγ downregulates BMP signalling by reducing phosphorylation of downstream effectors Smad1/5/8. In this way, palovarotene prevents chondrogenesis and heterotopic ossification in FOP, and enables normal muscle tissue repair or regeneration to take place, reducing damage to muscle tissue.
What post-market commitments will the sponsor undertake
- Sohonos (palovarotene) is to be included in the Black Triangle Scheme. The PI [Product Information] and CMI [Consumer Medicines Information] for Sohonos 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 Sohonos EU [European Union] -risk management plan (RMP) (version 5.0, dated 7 April 2023, data lock point 27 April 2022), with Australia-specific annex (version 3.0 dated 25 July 2023), included with Submission PM-2022-03518-1-5, 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 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 ([Revision] 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.
Further information
The latest Product Information (PI) and Consumer Medicines 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.