Chemistry
Sargramostim is a recombinant version of GM-CSF, which is a glycoprotein made of 127 amino acids; sargramostim is mixture of three versions of GM-CSF that have molecular weights of 19,500, 16,800 and 15,500 Daltons. It is manufactured in yeast. History
The sequence of human GM-CSF was first identified in 1985 and soon three recominbant human GM-CSFs were produced, one in bacteria, one in mammalian cells, and one in yeast; Immunex developed GM-CSF manufactured in yeast into Leukine. Clinical trials of sargramostim were initiated in 1987; in that same year it was administered to six people as part of a compassionate-use protocol for the victims of cesium irradiation from the Goiânia accident.It was approved by the FDA in March 1991 under the trade name Leukine for acceleration of white blood cell recovery following autologous bone marrow transplantation in patients with non-Hodgkins lymphoma, acute lymphocytic leukemia, or Hodgkins disease. In November 1996, the FDA also approved sargramostim for treatment of fungal infections and replenishment of  white blood cells following chemotherapy. A liquid formulation was approved in 1995. Immunex was acquired by Amgen in 2002. As part of the acquisition,  Leukine was spun off to Berlex, which became Bayer HealthCare in 2007.In January 2008, Bayer informed healthcare professionals of the market withdrawal of the current liquid formulation of sargramostim.
The liquid formulation was withdrawn because of an upward trend in spontaneous reports of adverse reactions, including syncope (fainting), which are temporally correlated with a change that was made to the formulation around April 2007 to include edetate disodium (EDTA). The upward trend in adverse reaction reporting rates had not been observed with the use of lyophilized sargramostim. The original liquid formulation without EDTA was returned to the market in the US in May 2008.In 2009, Genzyme acquired the rights to Leukine from Bayer, including the manufacturing facility in the Seattle area.In March 2018 the label was extended to use as a countermeasure for acute radiation syndrome. == References ==