Mecasermin
Rinfabate

Mecasermin rinfabate is a binary complex of recombinant human insulin-like growth factor-1 and recombinant human IGF-binding protein-3 (IGFBP-3), combined in equimolar proportions. In the circulation, most endogenous IGF-1 travels in a ternary complex with IGFBP-3 and the acid-labile subunit, which prolongs its half-life and limits the amount of free IGF-1 available to tissues. Mecasermin rinfabate was designed by Insmed to mimic this natural carrier arrangement, with the aim of extending IGF-1 exposure and moderating peaks in free hormone.

The product was approved by the FDA in 2005, marketed as Iplex, for severe primary IGF-1 deficiency. Following patent litigation with the makers of mecasermin, it was withdrawn from the US market for short stature, and the product has since been discontinued; it is not marketed in the EU. Despite its short commercial life, mecasermin rinfabate remains a useful historical case in research on binding-protein pharmacology, half-life extension through physiological carriers and the comparison of free versus bound IGF-1. It was also explored in other research settings, including studies in myotonic dystrophy.

Mecasermin rinfabate delivers IGF-1 bound to IGFBP-3. In the circulation, the complex can associate with the acid-labile subunit to form a ternary complex, recreating the main physiological reservoir of IGF-1. Bound IGF-1 is unable to activate receptors directly; it is released gradually as IGFBP-3 undergoes proteolysis or binds cell surfaces. Free IGF-1 then activates the IGF-1 receptor tyrosine kinase, stimulating PI3K-Akt and MAPK signalling and, at the growth plate, chondrocyte proliferation. The carrier is intended to prolong exposure while blunting abrupt rises in free IGF-1, which were hypothesised to contribute to hypoglycaemia.