INCRELEX

What it is

Increlex is mecasermin 10 mg/mL solution for injection, a recombinant DNA-derived human insulin-like growth factor-1 (IGF-1) produced in Escherichia coli. It is supplied as a solution for injection. This medicinal product is subject to additional monitoring in Australia.

Approved indications

— 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).

Dosing overview

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 clinical trials, optimal growth response was seen with doses between 0.08 mg/kg and 0.12 mg/kg twice daily. Doses greater than 0.12 mg/kg twice daily should not be exceeded as this may increase the risk of neoplasia. Increlex should be administered by subcutaneous injection shortly before or after a meal or snack. Treatment should continue until bone age demonstrates fusion of epiphysis.

Key safety warnings

There is an increased risk of benign and malignant neoplasia in children and adolescents treated with Increlex, since IGF-1 plays a role in the initiation and progression of benign and malignant tumours. There have been post-marketing reports of both benign and malignant neoplasms in children and adolescents who have received treatment with Increlex. Physicians should be vigilant of any symptoms of potential malignancy. If benign or malignant neoplasia develops, Increlex treatment should be discontinued definitely and appropriate expert medical care sought. It is recommended that patients have a skin check at baseline and regularly during treatment for the documentation of any naevi. Mecasermin may have insulin-like hypoglycaemic effects. It should be administered shortly before or during a meal or snack. Special attention should be paid to young children, children with a history of hypoglycaemia and children with inconsistent food intake. Blood glucose monitoring is recommended on initiation of treatment, during dose titration, periods of reduced oral intake or if the child is unwell. Patients should avoid engaging in any high-risk activities within 2–3 hours after dosing, particularly at the initiation of mecasermin treatment, until a well-tolerated dose of Increlex has been established. Lymphoid tissue hypertrophy associated with complications, such as snoring, sleep apnoea, and chronic middle-ear effusions have been reported with the use of this medicinal product. Patients should have examinations periodically and at the occurrence of clinical symptoms to rule out such potential complications or to initiate appropriate treatment. Echocardiogram is recommended before initiation of mecasermin treatment in all patients. Patients with abnormal echocardiogram findings or cardiovascular symptoms should be followed regularly with echocardiogram procedures.

Contraindications

Increlex is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients. Increlex is contraindicated in children and adolescents with active or suspected neoplasia, or any condition or medical history which increases the risk of benign or malignant neoplasia. As Increlex contains benzyl alcohol, it must not be given to premature babies or neonates.

PBS listing

Increlex solution for injection 40 mg in 4 mL (10 mg per mL) is listed on the PBS with one item. The restriction type is authority required, and the ex-manufacturer price is A$1024.00.

Regulatory history

Increlex mecasermin 10 mg/mL solution for injection was first listed on the ARTG on 22 November 2019. An AusPAR (Australian Public Assessment Report) was published on 19 November 2019 approving Increlex 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. The PBAC initially did not recommend Increlex in November 2021, but recommended it in March 2022 for primary insulin-like growth factor 1 deficiency in children and adolescents with growth failure.