Increlex
Registration timeline
The following table summarises the key steps and dates for this application.
| Description | Date |
|---|---|
| Orphan designation | 17 July 2018 |
| Submission dossier accepted and first round evaluation commenced | 3 October 2018 |
| First round evaluation completed | 1 March 2019 |
| Sponsor provides responses on questions raised in first round evaluation | 1 May 2019 |
| Second round evaluation completed | 17 July 2019 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 28 August 2019 |
| Sponsor's pre-Advisory Committee response | 16 September 2019 |
| Advisory Committee meeting | 4 October 2019 |
| Registration decision (Outcome) | 19 November 2019 |
| Completion of administrative activities and registration on ARTG | 22 November 2019 |
| Number of working days from submission dossier acceptance to registration decision* | 220 |
*Statutory timeframe for standard applications is 255 working days
Increlex is supplied as a multi-dose solution. Each vial is for use in one patient only.
Treatment with mecasermin should be under the supervision of a paediatric endocrinologist.
There should be documented confirmation of the diagnosis of severe IGF-1 deficiency at initiation of treatment, in line with guidance in the prescribing information (see section 4.1 Therapeutic Indications in Product Information). Ideally this will also include confirmation of mutation in the growth hormone/IGF signalling pathway consistent with severe IGF-1 deficiency.
The dose should be individualised for each patient. The recommended starting dose of mecasermin is 0.04 mg/kg of body weight twice daily by subcutaneous injection. If no significant adverse reactions occur for at least one week, the dose may be raised in increments of 0.04 mg/kg to the maximum dose of 0.12 mg/kg given twice daily. In the clinical trials, optimal growth response was seen with doses between 0.08 mg/kg and 0.12 mg/kg twice daily. Lower doses were less effective. Higher doses were more often associated with hypoglycaemia. Doses greater than 0.12 mg/kg twice daily should not be exceeded as this may increase the risk of neoplasia. (See Section 4.4 Special warnings and precautions for use in Product Information). If the recommended dose is not tolerated by the patient, treatment with a lower dose can be considered. Treatment success should be evaluated based on height velocities.
For further information refer to the Product Information.
Increlex (mecasermin) was approved for the following therapeutic use:
For the long-term treatment of growth failure in children and adolescents from 2 to 18 years with severe primary insulin-like growth factor 1 deficiency (Primary IGFD).
Severe Primary IGFD is defined by:
- Height standard deviation score ≤ -3.0 and
- Baseline height velocity less than the 25th percentile for bone age, based on two measurements over 12 months and
- Basal IGF-1 levels below the 2.5th percentile for age and gender and
- GH sufficiency.
- Exclusion of secondary forms of IGF-1 deficiency, such as malnutrition, hypopituitarism, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory steroids.
IGF-1 and GH levels must be performed using validated assays with paediatric normal ranges.
- Increlex (mecasermin) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Increlex 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 Increlex mecasermin European Union-Risk Management Plan (EU-RMP), version 11.3, dated 22 October 2019, (data lock point 31 January 2018), with Australian Specific Annex, version 3.0, dated 8 November 2019, included with submission PM-2018-03520-1-5, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.
Any changes to which the sponsor has agreed should be included in a revised RMP and ASA. However, irrespective of whether or not they are included in the currently available version of the RMP document, the agreed changes become part of the risk management system.
An obligatory component of risk management plans 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 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.
- For all injectable products the Product Information must be included with the product as a package insert.
- The Consumer Medicines Information must be included with the products as a package insert. The CMI should have a link to the full version of the PI on the TGA website.
- Batch release testing & compliance with Certified Product Details (CPD)
- All batches of Increlex imported into/manufactured in Australia must comply with the product details and specifications approved during evaluation and detailed in the Certified Product Details (CPD).
- Each batch of Increlex imported into/manufactured in Australia is not released for sale until samples and/or the manufacturer’s release data have been assessed and endorsed for release by the TGA Laboratories Branch. Outcomes of laboratory testing are published biannually in the TGA Database of Laboratory Testing Results.
- The sponsor should be prepared to provide product samples, reference materials and documentary evidence as defined by the TGA Laboratories Branch. The sponsor must contact Biochemistry.Testing@health.gov.au for specific material requirements related to the batch release testing/assessment of the product. More information on TGA testing of biological medicines is available at https://www.tga.gov.au/publication/testing-biological-medicines.
This batch release condition will be reviewed and may be modified on the basis of actual batch quality and consistency. This condition remains in place until you are notified in writing of any variation.