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| Primary information |
|---|
| ID | 15631 |
| Therapeutic ID | Th1614 |
| Protein Name | Mecasermin rinfabate |
| Sequence | >Th1614_Mecasermin_rinfabate
GPETLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA
|
| Molecular Weight | NA |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Half life ranges from 10 to 16 hours with a mean of 13 hours[F4054]. Mecasermin rinfabate is said to have a longer half life than [DB01277][A176065]. |
| Description | Mecasermin rinfabate is approved for severe primary insulin-like growth factor (IGF) deficiency or in patients with GH gene deletion who have developed antibodies to growth hormone (GH)[A176020]. Mecasermin rinfabate is similar to [DB01277] in that both drugs contain recombinant DNA origin insulin-like growth factor 1 (IGF-1). Mecasermin rinfabate however, is already bound to recombinant DNA origin insulin-like growth factor binding protein 3 (IGFBP-3)[A12605]. The binding of IGF-1 to IGFBP-3 is said to extend the half life and reduce the clearance of IGF-1 in patients with growth hormone resistant syndromes and low levels of IGFBP-3 though this may represent <500 patients worldwide[A176065]. Mecasermin rinfabate manufactured by Insmed Incorporated under the brand name Iplex was approved by the FDA in 2005[L5722]. In 2007 Insmed withdrew their application for a marketing authorization with The European Medicines Agency[F4075]. |
| Indication/Disease | Mecasermin rinfabate was approved for treatment of severe primary insulin-like growth factor (IGF) deficiency or in patients with GH gene deletion who have developed antibodies to growth hormone (GH)[A176020]. Severe primary IGF-1 deficiency is defined by:[FDA Label] A) height standard deviation (SD) score less than or equal to 3 SD below normal B) basal IGF-1 SD score less than or equal to 3 SD below normal C) normal or above normal levels of growth hormone In 2007, Insmed (Mecasermin rinfabate's manufacturer) made an agreement with Tercica (Mecasermin's manufacturer) that Mecasermin would no longer be available for this indication but could be developed for non short stature conditions such as severe insulin resistance, myotonic muscular dystrophy, and HIV associated adipose redistribution syndrome[A176125]. |
| Pharmacodynamics | Mecasermin rinfabate promotes vertical growth in pediatric patients in a similar fashion to [DB01277][FDA Label]. [DB01277] is a biosynthetic (recombinant DNA origin) form of human insulin-like growth factor 1 (IGF-1) designed to replace natural IGF-1 in pediatric patients who are deficient, promoting normalized statural growth[A2324]. Growth hormones (GH) bind to growth hormone receptors (GHR) in the liver and other tissues, which stimulates the synthesis of IGF-1. In target tissues, IGF-1 activates the IGF-1 receptor, resulting in intracellular signals that stimulate growth [A2323]. Although many actions of the GH are mediated through IGF-1, the precise roles of GH and IGF-1 have not been fully elucidated. Patients with severe primary IGF-1 deficiency (Primary IGFD) fail to produce adequate levels of IGF-1, due to disruption of the GH pathway used to promote IGF-1 release (possible GH pathway disruptions include mutations in the GHR, post-GHR signaling pathway, and IGF-1 gene defects[A176065]. The structure of IGFBP-3 remains unsolved[A176309]. |
| Mechanism of Action | Mecasermin rinfabate supplies recombinant-DNA-origin IGF-1 (rhIGF-1) bound to recombinant-DNA-origin IGFBP-3. 80% of IGF-1 is naturally bound to IGFBP-3 so the binding of rhIGF-1 to rhIGFBP-3 increases the half life of rhIGF-1 compared to [DB01277]. rhIGF-1 binds to the Type I IGF-1 receptor. This receptor exerts intra-cellular signaling activity in a number of processes involved in statural growth, including mitogenesis in multiple tissue types, chondrocyte growth and division along cartilage growth plates, and increases in organ growth[A2324]. |
| Toxicity | Studies on carcinogenicity, genotoxicity, animal fertility, fetal development, excretion in breast milk, and use in patients over 65 years have not been performed[FDA Label]. Use in pregnant, breast feeding, or geriatric populations should be avoided as there is a lack of safety data[FDA Label]. Animal reproductive toxicity studies have shown increased incidence of abortion, post implantation loss, fewer viable fetuses, and an increase in fetal skeletal abnormalities[F4054]. Insulin-like growth factor 1 (IGF-1) without insulin-like growth factor binding protein 3 (IGFBP-3) has been shown to not be mutagenic according to the Ames test and have no affect on fertility in rats given 7 times the maximum human recommended dose based on body surface area[FDA Label]. No studies have been performed in patients with impaired renal or hepatic function however these impairments are not expected to significantly affect the pharmacokinetics of Mecasermin rinfabate[F4054]. |
| Metabolism | There is little published data on the pharmacokinetics of Mecasermin rinfabate[A12605]. Mecasermin rinfabate is expected to degrade into small peptides and amino acids[F4054]. It is suspected that IGFBP-3 in Mecasermin rinfabate is broken down by serine proteases or metalloproteases[A12605]. |
| Absorption | There is little published data on the pharmacokinetics of Mecasermin rinfabate[A12605]. Mecasermin rinfabate is injected subcutaneously and distributes rapidly throughout the body, especially in well vascularized tissue[F4054]. |
| Approximately 1000mL/kg[F4054]. |
| Clearance | Clearance ranges from 50 to 56mL/hr/kg with a mean of 53mL/hr/kg[F4054]. Mecasermin rinfabate is said to have lower clearance than [DB01277][A176065] |
| Categories | Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Insulin-like growth factor 1 receptor,Insulin receptor,Cation-independent mannose-6-phosphate receptor |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |