Partner Therapeutics (PTx), announced the FDA approval of Leukine for the treatment of adult and pediatric patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome, or H-ARS). Leukine is the first drug for H-ARS to demonstrate an improvement in survival when initiated 48 hours after radiation exposure.
Acute Radiation Syndrome (ARS) (sometimes known as radiation toxicity or radiation sickness) is an acute illness caused by irradiation of the body by a high dose of penetrating radiation. H-ARS occurs when the radiation exposure results in the destruction of the stem cells resident in the bone marrow that generate and maintain the body's immune system increasing the risk of infection, bleeding, and death. Leukine has the potential to improve survival in patients with H-ARS by facilitating recovery of blood cells that are important in helping the body's immune system fight infection.
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Efficacy studies of Leukine could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons and approval of this use was based on government-sponsored efficacy studies conducted in animals. Leukine (7 mcg/kg/day) or placebo was initiated 48 hours after exposure to myelosuppressive doses of radiation expected to be fatal to 50-60% of in non-human primates at day 60, without requiring supportive whole blood transfusions or individualized antibiotics (36 animals per group). Leukine improved survival by 85% (78% vs 42%; p=0.0018) at day 60. In addition, in an exploratory cohort that received higher radiation exposures, myelosuppressive doses to be fatal in 70-80% of non-human primates at day 60, Leukine was also shown to improve survival: 61% survival (11/18) in the Leukine group compared to 17% survival (3/18) in the control group.1 Clinical studies of Leukine in patients undergoing autologous or allogeneic bone marrow transplantation which showed improvements in recovery of white blood cells, reduced incidence of severe and life-threatening infections, and improved survival were included as supportive data for this indication. In clinical studies of Leukine, the most commonly reported side effects with Leukine administration are fever, nausea, diarrhea, and vomiting. Hypersensitivity reactions and infusion-related reactions have been reported with Leukine injection. Patients, particularly those with pre-existing lung disease, should be closely observed for such events.
Leukine is a yeast-derived recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF). Leukine was initially approved in the United States in 1991 and has five hematology oncologic indications. The development of the H-ARS indication was funded completely with Federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under Contract No. HHSO100201300005I. Leukine received orphan designation for H-ARS in the U.S. in November 2016 and in April 2018 was granted 7 years exclusivity period for this indication. A supplemental biologics licensing application (sBLA) was filed with FDA in September 2017 requesting approval of Leukine for treatment of H-ARS. In December, the application was granted Priority Review.
"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" said Debasish Roychowdhury, PTx Chief Medical Officer. "This latest approval in H-ARS is the beginning of a new era for Leukine with important ongoing studies in immunotherapy of cancers2 and other chronic debilitating disorders."
The company also announced today that FDA has issued a biologic license to PTx which completes the regulatory process for the transfer of Leukine to PTx.