FDA Approves Sargramostim for Hematopoeic Acute Radiation Syndrome

The FDA approved sargramostim (Leukine) as a treatment for adult and pediatric patients with hematopoietic subsyndrome of acute radiation syndrome (H-ARS), which occurs when patients are acutely exposed to myelosuppressive doses of radiation.

Sargramostim is the first drug for H-ARS to demonstrate an improvement in survival when initiated 48 hours after radiation exposure. It is currently used to help increase the number and function of white blood cells after bone marrow transplantation for five hematology oncologic indications.

Acute Radiation Syndrome, also known as radiation toxicity or radiation sickness, is a severe illness caused by irradiation of the body by a high dose of penetrating radiation; hematopoietic syndrome of acute radiation syndrome occurs when radiation exposure results in the destruction of the stem cells that reside in the bone marrow. Since these stem cells generate and maintain the body's immune system, this condition could increase the risk of infection, bleeding and death among patients treated with radiation.

Sargramostim has the potential to treat hematopoietic syndrome of acute radiation syndrome by facilitating recovery of blood cells that are important in helping the body's immune system fight infection.

The agency’s approval was based on animal studies, as human trials could not be conducted for ethical and feasibility reasons. Clinical studies—designed to evaluate sargramostim in patients undergoing autologous or allogeneic bone marrow transplantation——showed improvements in recovery of white blood cells, reduced incidence of severe and life-threatening infections, and improved survival, which supported the FDA’s original approval of the drug. The most commonly reported side effects include fever, nausea, diarrhea, and vomiting.

"In this study Leukine not only showed improved survival despite initiating therapy two days after the radiation exposure but also demonstrated these beneficial effects on survival at both standard and higher doses of radiation," Debasish Roychowdhury, chief medical officer of PTx, the drug’s manufacturer, said in a statement.

Roychowdhury added that ongoing studies are being conducted to evaluate sargramostim in immunotherapy of cancers and other chronic debilitating disorders.

"Sometimes existing drugs are overlooked given the focus on developing new drugs. This creates the potential for missed opportunities. We are taking a different approach," added Colleen Mockbee, chief development officer of PTx.

"Since the initial approval of Leukine, our knowledge of the immune system, as well as a deeper understanding of GM-CSF as a therapeutic agent has led to new development opportunities including autoimmune pulmonary alveolar proteinosis, Alzheimer's disease, and combinations with immune-oncology agents in the treatment of cancer. The approval of Leukine in H-ARS is just the beginning. We believe Leukine has the potential to positively impact the lives of many more patients."