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Uvadex
Sponsor
Device/Product name
Uvadex
Active Ingredient
Methoxsalen
Date of decision
Published
Submission type
New chemical entity
ATC codes
D05AD02, D05BA02
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 Uvadex 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 | 28 September 2018 |
| First round evaluation completed | 1 March 2019 |
| Sponsor provides responses on questions raised in first round evaluation | 6 May 2019 |
| Second round evaluation completed | 20 June 2019 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 2 July 2019 |
| Sponsor's pre-Advisory Committee response | 15 July 2019 |
| Advisory Committee meeting | 1-2 August 2019 |
| Registration decision (Outcome) | 13 September 2019 |
| Completion of administrative activities and registration on ARTG | 16 September 2019 |
| Number of working days from submission dossier acceptance to registration decision* | 184 |
*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
Concentrated injection
Strength
200 µg/10 mL
Other ingredients
Ethanol; propylene glycol; glacial acetic acid; sodium acetate trihydrate; sodium chloride; sodium hydroxide; water for injection. The drug product formulation contains 4.1% w/v ethanol and each 1 mL of Uvadex contains 40.55 mg of ethanol.
Containers
Vial
Pack sizes
12 vials
Routes of administration
Extracorporeal circulation via photopheresis
Dosage
Three extracorporeal photopheresis (ECP) treatments in the first week then two ECP treatments per week for at least 12 weeks, or as clinically indicated.
For further information refer to the Product Information.
Pregnancy category
Category DDrugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.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
Uvadex (methoxsalen) was approved for the following therapeutic use:
Uvadex (methoxsalen) is indicated for extracorporeal administration with the Therakos Cellex Photopheresis System for the treatment of steroid-refractory and steroid-intolerant chronic graft versus host disease (cGVHD) in adults following allogeneic HSC transplantation.
What is this medicine and how does it work
Methoxsalen is a naturally occurring photoactive substance found in the seeds of the Ammi majus (Umbelliferae) plant. It belongs to a group of compounds known as psoralens or furocoumarins.Uvadex is used in combination with the Therakos Cellex Photopheresis System to extracorporeally treat leukocyte enriched buffy coat. Although extracorporeal photopheresis (ECP) with methoxsalen has been used clinically for many years, knowledge regarding the full mechanism underlying ECP has not been fully elucidated. It is generally accepted that the molecular processes which lead to apoptotic cell death involve the intercalating of methoxsalen into the double-stranded DNA molecule within the nucleus.On activation by exposure to UVA light, methoxsalen binds to the pyrimidine bases of the nucleic acid (thymine, cytosine and uracil) and forms covalent cross-links between the two DNA strands. The formation of these photoadducts results in the proliferative arrest and death of lymphocytes. In addition, studies have demonstrated that photopheresis may result in the induction of an autoregulatory host response which recognizes and specifically suppresses photo-treated effector T-cell populations.
What post-market commitments will the sponsor undertake
The following specific conditions of registration apply to this approval:
- Uvadex (methoxsalen) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Uvadex 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 methoxsalen Australian-Risk Management Plan (Aus-RMP) (version 3.0, dated 15 April 2019, data lock point 25 February 2018), included with submission PM-2018-03515-1-2, 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).
As agreed between the TGA and the supplier who is the recipient of the approval, annual PSURs with the data lock point of 25th February are to be provided until the period covered by such reports is not less than three years from the date of this 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 and submitted to the TGA within ninety calendar days of the data lock point for that report.
- For all injectable products the Product Information must be included with the product as a package insert.