FDA Approved Growth Hormone Axis

Mecasermin

also known as: Increlex, rhIGF-1, recombinant IGF-1, somatomedin C

Ipsen's recombinant human IGF-1 (Increlex) — FDA-approved in 2005 for severe primary IGF-1 deficiency; the direct replacement for IGF-1 in patients whose own IGF-1 production is inadequate despite normal GH levels.

Recombinant human insulin-like growth factor 1 (rhIGF-1), a 70-amino-acid single-chain peptide identical in sequence to endogenous IGF-1, produced in E. coli. FDA-approved as Increlex in August 2005 for the long-term treatment of growth failure in children with severe primary IGF-1 deficiency (Laron syndrome, GH receptor defects, post-GH antibody states) or with GH gene deletion who have developed neutralizing antibodies to GH. Provides IGF-1 replacement when the patient cannot generate it from exogenous GH. Acquired by Ipsen from Tercica; marketed as Increlex in most countries.

Mechanism of action

Binds the IGF-1 receptor (IGF-1R), a tyrosine kinase receptor structurally related to the insulin receptor, triggering autophosphorylation and activation of PI3K/Akt and Ras/MAPK signaling to drive anabolic growth effects on bone (longitudinal growth via chondrocyte proliferation), muscle, and other tissues. Also activates the IGF-1R / insulin receptor hybrid receptor and, at high concentrations, the insulin receptor itself — which is the basis for the hypoglycemia risk that is the primary safety concern in dosing.

Primary uses

  • Severe primary IGF-1 deficiency in children
  • GH gene deletion with neutralizing antibodies to GH

Typical dosing

0.04–0.12 mg/kg twice daily twice daily (subcutaneous)

Start at 0.04–0.08 mg/kg twice daily; titrate by 0.04 mg/kg increments to maximum 0.12 mg/kg twice daily. Must be administered with a meal or snack to mitigate hypoglycemia risk. Dose-limiting adverse effect is hypoglycemia; tonsillar/adenoidal hypertrophy is a class characteristic.

Regulatory status

FDA-approved August 2005 as Increlex (Tercica, later Ipsen) for the long-term treatment of growth failure in children with severe primary IGF-1 deficiency or with GH gene deletion who have developed neutralizing antibodies to GH. EMA approval August 2007 (conditional, later full). Not approved for idiopathic short stature or for use in children with normal IGF-1 levels.

References

  1. [fda-pi] Increlex (mecasermin) Prescribing Information. Ipsen Biopharmaceuticals.
  2. [pubmed] Chernausek SD, et al. "Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity." J Clin Endocrinol Metab, 2007;92:902-910.
  3. [review] Backeljauw PF, et al. "Therapy for 6 years with recombinant human insulin-like growth factor-I in children with severe primary IGF-I deficiency." J Clin Endocrinol Metab, 2013;98:3440-3447.

Related peptides

Somatropin (HGH)

FDA-approved recombinant human growth hormone — the direct hormone replacement, with multiple clinical indications, prescription-only status, and specific federal criminal provisions against off-label distribution.

Mecasermin rinfabate

Insmed's IGF-1 / IGFBP-3 complex (iPlex) — briefly FDA-approved in 2005 for severe primary IGF-1 deficiency; discontinued in 2008 after a labeling/patent injunction that resolved the competitive dispute between Tercica's Increlex and Insmed's iPlex in favor of Increlex.

IGF-1 LR3

A 13-amino-acid N-terminal extension plus Arg3 substitution gives IGF-1 LR3 roughly 2–3× the potency of native IGF-1 in bioassays — a research-reagent favorite that became a bodybuilding staple despite no human approval.

IGF-1 DES(1-3)

Deleting the first three amino acids of IGF-1 cripples IGFBP binding while preserving receptor activity — giving DES(1-3) roughly 10× the in vitro potency of native IGF-1 at promoting cell growth in IGFBP-rich environments.
Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.