Discontinued Growth Hormone Axis

Mecasermin rinfabate

also known as: iPlex, rhIGF-1/rhIGFBP-3, IGF-1/IGFBP-3 complex

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.

A recombinant 1:1 molar binary complex of human IGF-1 and IGFBP-3 (its principal circulating binding protein), developed by Insmed as an alternative to free rhIGF-1 that was intended to provide IGF-1 replacement with a longer effective half-life and a lower hypoglycemia risk. FDA-approved December 2005 as iPlex for severe primary IGF-1 deficiency. A 2007–2008 patent litigation and FDA/court-imposed labeling restrictions effectively removed iPlex from the growth indication market in favor of Increlex; Insmed divested the program in 2008 and the product was discontinued. Included here for reference because it remains a cited archetype of IGF-1/IGFBP complex therapy.

Mechanism of action

Same IGF-1R agonism as free rhIGF-1, but delivered as a preformed IGF-1 / IGFBP-3 binary complex. The complex slows renal clearance, buffers the acute post-dose insulin-receptor-mediated hypoglycemia effect, and resembles the physiological circulating form of IGF-1 (which is almost entirely bound to IGFBP-3 and acid-labile subunit in a ternary complex).

Primary uses

Severe primary IGF-1 deficiency (historical, 2005–2008)
Investigated in ALS and myotonic dystrophy (not approved)

Typical dosing

0.5–2.0 mg/kg/day once or twice daily (subcutaneous)

Historical dosing; not currently available for clinical use.

Regulatory status

FDA-approved December 2005 as iPlex (Insmed) for severe primary IGF-1 deficiency. Patent litigation with Tercica (Increlex) 2006–2008 led to an injunction and labeling restrictions limiting iPlex marketing for the growth indication. Insmed divested the program to Ipsen in 2009; commercial distribution for growth indications ended. Small-scale off-label use in ALS and myotonic dystrophy was later explored without reaching approval.

References

[pubmed] Kemp SF, et al. "Efficacy and safety results of long-term therapy with recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 complex in children with severe primary IGF-1 deficiency." Horm Res Paediatr, 2013;80:275-281.
[manufacturer] Insmed Incorporated. SEC filings and press releases regarding iPlex, 2005–2009.

Related peptides

Mecasermin

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.

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.

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.

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.