Scientists have reported that Tekmira Pharmaceuticals Corp.'s experimental drug candidate TKM-Marburg (NP-718m–LNP) was able to prevent monkeys from becoming seriously ill after Marburg virus infection, even when treatment was not started until the animals showed signs of viremia.

They published their work in the Aug. 21, 2014, issue of Science Translational Medicine.

Senior author Thomas Geisbert, who is at the University of Texas Medical Branch, told reporters at a press conference announcing the findings that the late treatment onset demonstrated the "real world utility" of the technology, giving hope that effective treatments for Marburg, as well as its currently attention-hogging cousin Ebola, could be developed.

The technological approach used in the present studies, siRNA delivered in a lipid nanoparticle, also has been used to protect Macaque monkeys from death due to Ebola infection, although in the earlier Ebola study the drug was given soon after exposure.

Therapeutics for hemorrhagic viruses are developed under the FDA's two animal rule; that is, for FDA approval they have to be effective in two animal species and safe in humans.

With the new paper, data in two animals – guinea pigs and monkeys – exists for the Marburg drug.

Geisbert said it would take "less than a year, probably, for a clinical trial, but it really depends – we don't have the funding . . . today for a clinical trial for the Marburg product."

The experimental Ebola drug, on the other hand, had satisfied the two-animal rule in 2010 – but at the time, funding for human trials was not forthcoming, though a clinical trial is now being funded through the Department of Defense.

In their experiments, Geisbert and his colleagues at the University of Texas and Tekmira used siRNAs delivered in lipid nanoparticles to block translation of Marburg virus mRNA.

The sequences used in the study were targeted to conserved sequences of Marburg virus and would be expected to be effective against all major strains. MARV-Angola, the strain used to test in the work now reported in Science Translational Medicine is the deadliest known, with fatality rates of about 90 percent in the 2005 outbreak that was due to this particular strain.

Geisbert and his team infected monkeys with high levels of MARV-Angola and began treatment with TKM-Marburg between 30 minutes and three days after infection.

Even when treatment was not started until the third day, TKM-Marburg completely protected the animals. None of the treated animals died, and only a few of them even developed a fever or rash.

The experimental setup does not wholly mirror the course an infection with Marburg virus would take in the real world, due to both ethical and financial imperatives to minimize the number of primates used. Geisbert estimated that the third day after experimental infection would be equivalent to the sixth or seventh day after a naturally occurring infection.

But the key point, he added, was that treatment was not initiated until there were detectable signs that an infection had occurred. The team currently is testing how long treatment can be delayed and still be effective.

The company's TKM-Ebola also could be complementary to Zmapp, Mapp Biopharmaceutical Inc.'s experimental Ebola drug. Zmapp is a cocktail of monoclonal antibodies that works by blocking viral entry, whereas the siRNA sequences in TKM-Ebola block replication.

There is an NIH-funded study under way to look at whether combining the two drugs could be beneficial, much like in the HIV fight, where, Geisbert said, "you've seen a lot of advances . . . when people started combining treatments that operated by different mechanisms."

For all its promise, the work also illustrated some nonscientific challenges in fighting emerging pathogens: There are a number of them. It's difficult to know which one is going to be the next big problem until people start falling ill and, in the absence of an acute outbreak, it is very tough to secure funding to move promising agents through the pipeline.

At least in theory, the development of broad-spectrum agents that could fight, for example, filoviruses in general would be an alternative approach that might be more attractive economically. But Geisbert said that in practice, that approach has simply not panned out.

"We've tried that," he told BioWorld Today. "I mean, I've got shelves and shelves and shelves of things that look great in small animal models, but don't work in monkeys. And I think that we've kind of as a field moved toward these more specific treatments because they work, because the nonhuman primate has been the high bar and the gold standard, and kind of we felt that if you can't protect the monkeys, it's probably going to be a real challenge to get it approved for licensure for use in a human."