Rybrevant
Registration timeline
This evaluation was facilitated through Project Orbis, an initiative of the United States (US) Food and Drug Administration (FDA) Oncology Center of Excellence (OCE). Under this project, the FDA, Health Canada (HC), Medicines and Healthcare products Regulatory Agency (MHRA) and the TGA collaboratively reviewed the application. This innovative evaluation process provided a framework for process alignment and management of evaluation issues in real-time across jurisdictions.
Each regulator agency maintained its regulatory process to make independent decisions about the approval (market authorisation).
The following table summarises the key steps and dates for this application.
|
Description |
Date |
|
Designation (Provisional) |
5 October 2021 |
|
Submission dossier accepted and first round evaluation commenced |
30 November 2021 |
|
First round evaluation completed |
3 May 2022 |
|
Sponsor provides responses on questions raised in first round evaluation |
31 May 2022 |
|
Second round evaluation completed |
1 August 2022 |
|
Delegate’s Overall benefit-risk assessment |
15 September 2022 |
|
Sponsor’s pre-Advisory Committee response |
Not applicable |
|
Advisory Committee meeting |
Not applicable |
|
Registration decision (Outcome) |
28 November 2022 |
|
Completion of administrative activities and registration on ARTG |
1 December 2022 |
|
Number of working days from submission dossier acceptance to registration decision* |
213 |
*Statutory timeframe for standard applications is 255 working days
Disodium edetate, histidine hydrochloride monohydrate, histidine, methionine, polysorbate 80, sucrose and water for injections
Rybrevant should be administered by a healthcare professional in a setting with appropriate medical support for the management of infusion-related reactions (IRRs), including equipment for cardiorespiratory resuscitation. See Section 4.4 [of Product Information] Special warnings and precautions for use.
Administer pre-infusion medications (see Section 4.2 [of Product Information] Pre-infusion medications).
When considering the use of Rybrevant, the presence of an EGFR [epidermal-growth factor receptor] exon 20 insertion mutation should be established using a validated test (see Section 5.1 [of Product Information] Clinical trials).
The recommended dose of Rybrevant is according to the body weight of patient. See section 4.2 [of Product Information] for the recommended dose, dosing schedule and infusion rates of Rybrevant. Administer Rybrevant until disease progression or unacceptable toxicity.
For further information refer to the Product Information.
Drugs 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
Rybrevant (amivantamab) was approved for the following therapeutic use:
The provisionally approved new indication(s) for the medicine(s) are:
Rybrevant has provisional approval for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that has an activating epidermal-growth factor receptor (EGFR) exon 20 insertion mutation, whose disease has progressed on or after platinum-based chemotherapy.
The decision to approve this indication has been made on the basis of objective response rate and duration of response in a single arm study. Continued approval of this indication depends on verification and description of benefit in a confirmatory study.
The full indications are now:
Rybrevant has provisional approval for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that has an activating epidermal-growth factor receptor (EGFR) exon 20 insertion mutation, whose disease has progressed on or after platinum-based chemotherapy.
The decision to approve this indication has been made on the basis of objective response rate and duration of response in a single arm study. Continued approval of this indication depends on verification and description of benefit in a confirmatory study.
In preclinical studies, amivantamab disrupted EGFR and MET signalling functions through blocking ligand binding and, in exon 20 insertion mutation models, enhancing degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumour cells also allows for targeting of these cells for destruction by immune effector cells, such as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity (ADCC) and trogocytosis mechanisms, respectively.
- Rybrevant (amivantamab) is to be included in the Black Triangle Scheme. The PI [Product Information] and CMI [Consumer Medicines Information] for Rybrevant must include the black triangle symbol and mandatory accompanying text for five years, or the product’s entire period of provisional registration, whichever is longer.
- The Rybrevant EU [European Union]-risk management plan (RMP) (version 1.2, dated 9 December 2021, data lock point 30 March 2021), with Australia-specific annex (version 2.0, dated 28 September 2022), included with Submission PM-2021-04814-1-4, 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, or the entire period of provisional registration, whichever is longer.
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.
- Confirmatory trial data (as identified in the sponsor’s plan to submit comprehensive clinical data on the safety and efficacy of the medicine before the end of the 6 years that would start on the day that registration would commence) must be provided.
Specifically the sponsor must conduct studies as described in the clinical study plan in version 2.0 (dated 28 September 2022) of the Australia-specific annex. The following study reports should be submitted to TGA:
-
- The final clinical study report for Study 61186372EDI1001 (CHRYSALIS), if it changes the data reflected in the TGA approved product information to a clinically relevant extent.
- The final clinical study report for Study 61186372NSC3001 (PAPILLON), anticipated to be available for submission in Q1 [first quarter of] 2024.
Further guidance for sponsors is available on the TGA website.
- For all injectable products the Product Information must be included with the product as a package insert.