Sargramostim

Sargramostim
Clinical data
AHFS/Drugs.com Monograph
MedlinePlus a693005
ATC code L03AA09 (WHO)
Legal status
Legal status
  • ℞ (Prescription only)
Identifiers
CAS Number 83869-56-1 YesY
DrugBank DB00020 YesY
ChemSpider none
UNII 5TAA004E22 YesY
ChEMBL CHEMBL1201670 N
Chemical and physical data
Formula C639H1006N168O196S8
Molar mass 14434.5 g/mol
 NYesY (what is this?)  (verify)

Sargramostim (marketed by Genzyme under the tradename Leukine) is a recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) that functions as an immunostimulator.[1]

It is produced in yeast.[2]

Therapeutic uses

Sargramostim is primarily used for myeloid reconstitution after autologous or allogeneic bone marrow transplantation. It is also used to treat neutropenia induced by chemotherapy during the treatment of acute myeloid leukemia. Sargramostim has recently shown promise in treating Crohn's disease and other GI inflammatory disorders. This medication is being investigated in trials to treat autoimmune pulmonary alveolar proteinosis (PAP).[3] It is also being investigated in combination with oncolytic reovirus in brain cancer. [4]

Contraindications

Sargramostim should not be used in patients with excessive leukemic myeloid blasts in the bone marrow or peripheral blood (≥ 10%), in patients with known hypersensitivity to GM-CSF, yeast-derived products or any component of the product and for concomitant use with chemotherapy and radiotherapy.

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;[5] Immunex developed GM-CSF manufactured in yeast into Leukine.[6] Clinical trials of sargramostim were initiated in 1987;[7] 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.[8]

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-Hodgkin's lymphoma, acute lymphocytic leukemia, or Hodgkin's disease.[9] In November 1996, the FDA also approved sargramostim for treatment of fungal infections and replenishment of white blood cells following chemotherapy.[10] A liquid formulation was approved in 1995.[6] Immunex was acquired by Amgen in 2002.[7] As part of the acquisition, Leukine was spun off to Berlex, which became Bayer HealthCare in 2007.[6] In 2009, Genzyme acquired the rights to Leukine from Bayer, including the manufacturing facility in the Seattle area.[7][11][12]

Liquid formulation - withdrawn

On January 23, 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).[6] The upward trend in adverse reaction reporting rates had not been observed with the use of lyophilized sargramostim.[13] The original liquid formulation without EDTA was returned to the market in the US in May 2008.[14]

References

  1. ↑ Kirman I, Belizon A, Balik E, et al. (2007). "Perioperative sargramostim (recombinant human GM-CSF) induces an increase in the level of soluble VEGFR1 in colon cancer patients undergoing minimally invasive surgery". European Journal of Surgical Oncology. 33 (10): 1169–1176. doi:10.1016/j.ejso.2007.03.014. PMID 17512160.
  2. ↑ Beveridge RA, Miller JA, Kales AN, et al. (1998). "A comparison of efficacy of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in the therapeutic setting of chemotherapy-induced myelosuppression". Cancer Invest. 16 (6): 366–373. doi:10.3109/07357909809115775. PMID 9679526.
  3. ↑ "Whole Lung Lavage (WLL)/Inhaled Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (PAP). Phase II/III trial 2009-2013". Clinicaltrials.gov. Retrieved 2012-06-20.
  4. ↑ "Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Recurrent or Refractory Brain Tumors.". Clinicaltrials.gov. Retrieved 2015-05-14.
  5. ↑ Armitage, JO (15 December 1998). "Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor.". Blood. 92 (12): 4491–508. PMID 9845514.
  6. 1 2 3 4 Staff (May 2008). "Back to the Future: Original Liquid Leukine® Coming Soon" (PDF). Oncology Business Review.
  7. 1 2 3 "Immunex Corporation". Company Histories & Profiles. FundingUniverse.com. Retrieved 12 November 2011.
  8. ↑ Schmeck HM (1987-11-02). "Radiation Team Sent to Brazil Saves Two With a New Drug". New York Times. Retrieved 2012-06-20.
  9. ↑ "Approval Summary for sargramostim". Oncology Tools. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. 1991-03-05. Archived from the original on 2007-09-29. Retrieved 20 September 2009.
  10. ↑ "Newly Approved Drug Therapies (179): Leukine (sargramostim), Immunex". CenterWatch. Retrieved 2008-10-12.
  11. ↑ "Bayer Healthcare Pharmaceuticals Plant, Snohomish County, Washington State". pharmaceutical-technology.com. Retrieved 12 November 2011.
  12. ↑ "Genzyme and Bayer HealthCare Enter New Strategic Agreement". Genzyme. March 31, 2009. Retrieved 12 November 2011.
  13. ↑ "MedWatch Safety Alerts for Human Medical Products" (PDF). Fda.gov. 2008-11-06. Retrieved 2012-07-07.
  14. ↑ Chi, Judy (May 21, 2008). "Bayer launches Leukine without EDTA". Drug Topics.
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