NIAID-funded research has expanded the toolbox of medical countermeasures available in case a catastrophic event exposes people to high doses of radiation. Such an event could be a nuclear explosion, an accident at a nuclear reactor, a radiotherapy accident, or the escape of radioactive waste. In January, the Food and Drug Administration approved the use of romiplostim (trade name Nplate) to increase survival of adults and children, including newborns, who are acutely exposed to high doses of radiation that damage the bone marrow.
Romiplostim’s approval is the result of a collaboration between NIAID, the Biomedical Advanced Research and Development Authority (BARDA), and Amgen, which manufactures the drug. The FDA’s decision was based largely on NIAID-supported studies showing that romiplostim greatly increases survival in an animal model of radiation exposure.
Whole-body exposure to high doses of radiation can injure multiple tissues and organs, but the rapidly dividing cells of the bone marrow are among the most sensitive to radiation damage. Radiation-induced bone marrow damage reduces the number of pathogen-fighting neutrophils and clot-forming platelets in the blood, which can lead to death from infection or excessive bleeding. This is known as the hematopoietic subsyndrome of acute radiation syndrome, or H-ARS.
While the other approved drugs for H-ARS promote growth of white blood cells such as neutrophils, romiplostim works differently by increasing platelet counts, helping reduce the risk of radiation-induced hemorrhage. The drug was originally licensed in 2008 for the treatment of immune thrombocytopenia, a disorder characterized by abnormally low levels of platelets, and still is widely used for this purpose.
Because testing of romiplostim’s ability to treat H-ARS could not be done ethically in humans, the drug was approved under FDA’s Animal Rule, a regulation that permits approval based on efficacy testing in animals and safety testing in humans. Using a rhesus monkey model, researchers found that romiplostim more than doubled survival 60 days after acute radiation injury, from 32.5% among animals that received a placebo to 72.5% among animals that received romiplostim.
In the study, 80 monkeys exposed to a life-threatening dose of radiation were randomly assigned to receive a single injection of either romiplostim or placebo one day after radiation exposure. All animals were given standard supportive care, including fluids, anti-ulcer medication, anti-nausea medication, pain medication, and antibiotics. After 60 days, 29 of 40 monkeys in the romiplostim group had survived compared to 13 of 40 in the placebo group.
Encouragingly, scientists also found that the survival benefit of romiplostim appeared additive to that of an existing approved H-ARS drug. An additional 40 animals received doses of romiplostim and pegfilgrastim, which promotes neutrophil growth, one day and eight days following radiation exposure. Survival after 60 days in this group was 87.5%, suggesting that the combination may offer even greater benefit than romiplostim alone.
With the recent approval of romiplostim, FDA has now granted four approvals for products to treat H-ARS, three of which relied on NIAID-supported preclinical data. Previously, NIAID-funded research contributed to the 2015 approvals of filgrastim (Neupogen) and pegfilgrastim (Neulasta) for an H-ARS indication.