Peptide education
Mecasermin
Increlex · Recombinant human IGF-1 · rhIGF-1
Mecasermin is recombinant human insulin-like growth factor 1, or IGF-1. Increlex is used for growth failure in children aged two years and older with severe primary IGF-1 deficiency or a specific growth-hormone gene deletion with neutralizing antibodies to growth hormone.
In a predominantly open-label study of 76 children with growth-hormone insensitivity, the first-year comparison used pretreatment growth data from 59 children in a group with little or no previous IGF-1 treatment. Their average height velocity increased from 2.8 to 8.0 cm per year. Growth rates were lower in subsequent years.
Overview
Quick answer
Severe primary IGF-1 deficiency has specific height, IGF-1, and growth-hormone criteria. The label does not cover secondary IGF-1 deficiency caused by factors such as growth-hormone deficiency, malnutrition, or hypothyroidism.
What is mecasermin?
It is a manufactured form of human IGF-1, a hormone involved in linear growth. Increlex supplies IGF-1 for children with certain severe deficiencies.
Which children does the US label include?
Children aged two years and older with growth failure and severe primary IGF-1 deficiency, or with growth-hormone gene deletion who have developed neutralizing antibodies to growth hormone.
Why is it given near a meal or snack?
Mecasermin can lower blood glucose. The label describes giving it within 20 minutes before or after food and withholding a dose when the child cannot eat.
Is it a substitute for growth hormone?
The label says Increlex is not a substitute for growth hormone in its approved indications. It is also not indicated for secondary IGF-1 deficiency.
What other risks matter?
The label describes intracranial hypertension, enlarged tonsils or adenoids, slipped capital femoral epiphysis, scoliosis progression, and reported malignancies. It states that the relationship to new malignancy is unknown.
Evidence
Evidence snapshot
Increlex is labeled for growth failure in children aged two years and older who meet the specified criteria.
Among 59 children in the study's treatment-naive group with pretreatment growth data, mean height velocity rose from 2.8 to 8.0 cm per year during the first treatment year.
The label ties dosing to meals or snacks and recommends glucose monitoring during treatment initiation.
The label contraindicates use with closed epiphyses, malignancy or a history of malignancy, and known hypersensitivity.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| Mecasermin treats every cause of short stature. | The US indication is limited to specific causes of pediatric growth failure. The label excludes secondary IGF-1 deficiency and does not substitute for growth hormone in approved GH indications. | Diagnosis and label criteria determine the relevant treatment population. |
| The first-year growth result predicts every child's adult height. | The study enrolled 76 children and used pretreatment growth measurements from 59 children in its treatment-naive group for the first-year comparison. First-year velocity was not final height. | The result describes a group average over one treatment year. |
| Hypoglycemia is only a minor concern. | The label reports severe hypoglycemia, including seizures, and calls for dosing around food and glucose monitoring at treatment initiation. | Low blood glucose can be serious and is central to treatment monitoring. |
| Reports of malignancy prove mecasermin caused cancer. | Malignancies have been reported in treated children, including patients with underlying cancer-predisposing conditions. The label says a causal relationship to newly occurring malignancy is unknown. | The reports warrant monitoring; the label does not establish causation. |
Bottom line
Main takeaway
Mecasermin supplies IGF-1 for children with certain severe growth disorders, and treatment is timed around food because blood sugar can fall.
Severe primary IGF-1 deficiency and the separate GH-gene-deletion indication have specific label criteria.
The long-term growth study was predominantly open-label and compared growth velocity with pretreatment measurements.
Identity
What it is
Mecasermin is recombinant human IGF-1. IGF-1 contributes to growth signaling, and Increlex is given by subcutaneous injection in the label-defined pediatric conditions.
Severe primary IGF-1 deficiency is defined in the label by height and basal IGF-1 standard deviation scores at or below minus 3, with normal or elevated growth hormone.
Use context
Routes, doses, and cycle patterns
The Increlex label describes twice-daily subcutaneous treatment supervised by a clinician experienced in these pediatric growth conditions. Food timing and glucose monitoring are part of the labeled regimen.
Human studies and product labels
Increlex label
- Purpose
- Growth failure in children aged two years and older with label-defined conditions
- Context
- US prescribing information
- Route
- Subcutaneous
- Amount
- Starting dose 0.04 to 0.08 mg/kg per dose; maximum 0.12 mg/kg per dose
- Frequency
- Twice daily
The label allows an increase of 0.04 mg/kg per dose after at least one week if well tolerated. Doses are given within 20 minutes before or after a meal or snack; a dose is withheld when the child cannot eat.
Growth-hormone insensitivity study
- Purpose
- Growth in children with IGF-1 deficiency due to growth-hormone insensitivity
- Context
- Predominantly open-label long-term study
- Route
- Subcutaneous
- Amount
- 60 to 120 mcg/kg per dose
- Frequency
- Twice daily
- Duration
- Follow-up for up to 12 years
The study compared height velocity during treatment with pretreatment growth in the same children.
Research
Research evidence
The long-term study included 76 children with growth-hormone insensitivity and IGF-1 deficiency. For 59 children in its treatment-naive group with pretreatment growth data, average height velocity was higher in the first treatment year than before treatment. Growth rates were lower in subsequent years.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Long-term growth-hormone insensitivity study | 76 children with IGF-1 deficiency due to growth-hormone insensitivity; 59 children in the treatment-naive group had pretreatment growth data for the first-year comparison | Predominantly open-label longitudinal study | Subcutaneous recombinant human IGF-1 twice daily | Mean height velocity increased from 2.8 to 8.0 cm per year in the first treatment year. | The comparison used pretreatment growth, not a randomized control. Study entry criteria included height and IGF-1 standard deviation scores below minus 2; the US label's definition of severe primary IGF-1 deficiency uses scores at or below minus 3. | Moderate for the studied rare-disease population |
Cautions
Safety and unknowns
- Severe hypoglycemia, including seizures, has occurred. The label connects dosing to meals or snacks and recommends glucose monitoring when treatment begins.
- The label warns about intracranial hypertension, tonsil and adenoid enlargement, slipped capital femoral epiphysis, and progression of preexisting scoliosis.
- Malignancies have been reported in treated children, but the label says a causal relationship to new malignancy is unknown. Current or past malignancy is a contraindication in the professional prescribing information. The FDA-approved patient information also says children with a condition that increases cancer risk should not receive Increlex.
- The label contraindicates use with closed growth plates and known hypersensitivity to the product.
Mechanism
How it is proposed to work
Mecasermin supplies IGF-1, a hormone that helps carry growth signals to body tissues.
IGF-1 acts through its receptor to support growth. It also has insulin-like effects on glucose, which help explain the risk of hypoglycemia.
Details
Technical details
Sources
References
- 1.
DailyMed. Increlex prescribing information
US pediatric indication, food-associated dosing, monitoring, contraindications, and clinical studies.
- 2.
doi:10.1210/jc.2006-1610 PMID:17192294
Predominantly open-label pediatric growth and safety study.