Although Neupogen—a cancer drug—has been indicated for people exposed to extreme radiation, it has to be refrigerated and must be injected or given intravenously. And, Whitnall notes, "it does have occasional severe side effects, so it does need to be administered under the care of an MD."
In the event of a natural disaster, accident or nuclear attack, the likelihood that these supplies—and the clinical environment in which to administer them—would be easily and rapidly accessible for people in the immediate vicinity is dubious.
Nevertheless, the Defense Department "wanted an injectable form of the drug, which could be used by first responders as well as military personnel in the battlefield," Maniar says. But a pill form would be much easier to distribute on a wider scale.
CBLB502 will need to be injected because it contains a protein that would be digested in the stomach if swallowed. Gudkov notes, however, that the liquid is very stable even at high temperatures.
Likewise, Ex-RAD has only been tested in humans via injection. But researchers are working on an oral formulation. They also have a device that would make it easy for people to inject it themselves. "We have developed an auto-injector where the volunteers could self-administer to mimic a real-life scenario where people would be administering the drug by themselves," Maniar says.
Pitching a medication that might be picked up by the government as a just-in-case measure does not always appeal to investors the same way a new blockbuster cholesterol drug might.
As Whitnall points out "none of these are Big Pharma," and although the government has been helping out with contracts and grants, assembling larger scale human trials to prove safety requires "a huge amount of money."
But broadening the application of some of these drugs might eventually be able to generate additional interest. As Whitnall notes, "there are a lot of patients who need their blood system stimulated."
Some of them could also find a home in cancer treatment regimens. Animal and in vitro research has shown that CBLB502 might be effective in helping to mitigate damage done to healthy cells during radiation therapy—without protecting the tumor cells. Researchers are not exactly sure why this seems to be the case. It might be that because the nuclear factor-kappa B (NF-kB) light chain–enhancer of activated B-cell signaling—which boosts the survival of progenitor cells in bone marrow as well as a resistance to cell death (apoptosis)—is already activated in tumor cells, the drug boosts it in healthy cells but cannot increase its activity any more in the tumor cells. But more work remains to be done. And those at Onconova note that they are not currently pursuing a cancer angle with Ex-RAD because the approval process is so different from the one they are currently undertaking for radiation sickness.
And new drug candidates are cropping up all the time. As Whitnall notes, they have had to develop an initial screening program just to prioritize which compounds to test further because they "only have the funds to test one or two a year." A next step will also include trying to "increase the efficacy [by] combining drugs with different mechanisms in hopes that there is some kind of synergy."
But the drugs will first have to be shown to be safe on their own.
Whitnall, who works with several of the drugs in development through his role at the AFRRI, says that he does not want to pick favorites to guess which drug might come up for approval first. But in all likelihood it will still be at least a couple years before any of these therapies are ready to battle against the effects of gamma rays. Cleveland BioLabs is aiming to submit CBLB502 to the FDA for approval by late 2012. Onconova hopes to be able to file for agency approval for Ex-RAD in 2013 at the earliest. And Cellerant isn't expecting to have enough data together to submit its compound for at least another four years.