Somatomedin-1 binding protein-3 [
insulin-like growth factor-1 binding protein-3,
SomatoKine] is a recombinant complex of
insulin-like growth factor-1 (rhIGF-1) and binding protein-3 (IGFBP-3), which is the major circulating
somatomedin (
insulin-like growth factor) binding protein; binding protein-3 regulates the delivery of somatomedin-1 to target tissues. Somatomedin-1 binding protein-3 has potential as replacement
therapy for somatomedin-1 which may become depleted in indications such as major surgery, organ damage/failure and traumatic injury, resulting in catabolism. It also has potential for the treatment of
osteoporosis; diseases associated with
protein wasting including
chronic renal failure,
cachexia and severe
trauma; and to attenuate cardiac dysfunction in a variety of disease states, including after severe
burn trauma. Combined
therapy with somatomedin-1 and somatomedin-1 binding protein-3 would prolong the duration of action of somatomedin-1 and would reduce or eliminate some of the undesirable effects associated with somatomedin-1 monotherapy. Somatomedin-1 is usually linked to binding protein-3 in the normal state of the body, and particular
proteases clip them apart in response to stresses and release somatomedin-1 as needed. Therefore, somatomedin-1 binding protein-3 is a self-dosing system and
SomatoKine would augment the natural supply of these linked compounds. Somatomedin-1 binding protein-3 was developed by Celtrix using its proprietary
recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed
Pharmaceuticals on June 1 2000. Insmed and Avecia, UK, have signed an agreement for the manufacturing of
SomatoKine and its components,
IGF-1 and binding protein-3. CGMP clinical production of
SomatoKine and its components will be done in Avecia's Advanced Biologics Centre, Billingham, UK, which manufactures recombinant-based medicines and
vaccines with a capacity of up to 1000 litres. In 2003, manufacturing of
SomatoKine is planned to move to Avecia's larger facility with a capacity of 10 000 litres. Somatomedin-1 binding protein-3 was originally licenced to Welfide for Japan. On October 1 2001, Welfide Corporation merged with Mitsubishi-Tokyo
Pharmaceuticals to form Mitsubishi Pharma Corporation. The new company is a subsidiary of Mitsubishi Chemical. In April 2003 Insmed initiated a named patient programme in Europe, that will make available somatomedin-1 binding protein-3 for the treatment of
growth hormone insensitivity syndrome (GHIS)--
Laron syndrome. The treatment of patients was initiated in Scandinavia, with authorisation pending in several other European countries. Somatomedin-1 binding protein-3 will be made available to those GHIS patients who, in the opinion of their doctor, may benefit from
IGF-1 therapy. At precommercial scale quantities, the
drug will be available on a limited basis. Safety data generated from the named patient programme will be used to support marketing applications in 2004. A phase II dose-ranging study in children with GHIS was completed at Saint Bartholomew's and the Royal London School of Medicine, London, UK. A single dose of somatomedin-1 binding protein-3 delivered the same amount of
IGF-1 as two daily
injections of unbound
IGF-1. There were no adverse events reported. GHIS is a genetic condition in which patients do not produce adequate quantities of IGF because of a failure to respond to the
growth hormone signal. This results in a slower growth rate and short stature. Insmed has acquired an exclusive licence to Pharmacia's regulatory filings concerning yeast-derived
IGF-1. These filings were used by Pharmacia to receive marketing approvals in several European countries and also in the
investigational New Drug Application with the US FDA. This licence will facilitate the development of
SomatoKine for the treatment of children with GHIS. In January 2003, Insmed announced positive results from a double-blind, placebo-controlled, dose-ranging study of
SomatoKine in adolescent patients with
type 1 diabetes mellitus redolescent patients with
type 1 diabetes mellitus receiving
insulin therapy. The study was conducted at the University of Cambridge, Cambridge, UK, under the supervision of Professor D. Dunger. It has also been granted orphan drug status for the treatment of GHIS--
Laron syndrome in the US and in Europe. Celtrix has been granted 11 US patents for its
recombinant protein production technology, which it used for developing somatomedin-1 binding protein-3. Subsequently, Celtrix was acquired by Insmed
Pharmaceuticals on June 1 2000. Following the acquisition, Insmed announced that it intends to maintain the US rights to Celtrix's products portfolio. These US patents will expire between 2010 through 2017. Insmed is holding a US patent (expires in 2019) for the use of
SomatoKine in the treatment of both type 1 and
type 2 diabetes mellitus.