Experimental Drug May Stop Vascular Leak in Ebola

Veronica Hackethal, MD

December 24, 2014

An experimental drug developed to treat hemorrhagic shock may help treat vascular leakage symptoms in Ebola, according to a case study published online December 19 in the Lancet.

The drug is known as FX06 (MChE-F4Pharma), an experimental fibrin-derived peptide. Studies of FX06 in mice with dengue hemorrhagic shock have suggested the drug can reduce vascular leakage, a known physiologic effect of Ebola. A phase 2 clinical trial of FX02 used after myocardial infarction suggested the drug was well tolerated.

During Ebola infection, increased permeability of the vascular endothelium causes leakage of fluid, coagulation factors, and platelets into the tissues. This results in severe hypotension, edema, and tissue damage that can lead to multiorgan failure, the authors write.

Timo Wolfe, MD, from the Department of Medicine, Infectious Diseases Unit, University Hospital Frankfurt, Frankfurt/Main, Germany, and colleagues describe the case of a 38-year-old Ugandan male physician who survived after being evacuated to Germany for intensive care unit treatment. The patient was in charge of an Ebola virus treatment center in Lakka, Sierra Leona, where he tested positive for Ebola on September 28, 2014. After steadily worsening, the patient was airlifted to Germany on day 5, where he was treated under biosafety level 4 isolation conditions at University Hospital Frankfurt.

After 72 hours, the patient developed symptoms of vascular leak and multiorgan failure of the lungs, kidneys, and gastrointestinal tract.

The patient was intubated and placed on mechanical ventilation, as well as renal dialysis. He received 3 days of FX06 (from day 11 to 13) and improved from day 13 onward. He had undetectable viremia by day 19, was extubated on day 22, and fully recovered. He is now at home with his family, according to a press release.

During his treatment, the patient also received broad-spectrum antibiotics, norepinephrine, and the experimental drug favipiravir, an RNA polymerase inhibitor active against influenza.

Dr Wolf and colleagues mention another patient with Ebola who was airlifted to Leipzig and treated with FX06 from day 11 to 13. This patient died on day 13 from diffuse hemorrhage, without evidence of vascular leak syndrome.

"On the basis of our experience, we feel that FX06 warrants further evaluation in the treatment of vascular leak syndrome in Ebola virus disease," the authors write.

"We suggest FX06 as a potentially valuable therapeutic candidate for vascular leak syndrome in Ebola virus disease."

Without further study, however, no conclusions can currently be drawn because FX06 was used in only two patients, one of whom died, and there is no standard of care to which to compare FX06, according to Cameron Wolfe, MD, an assistant professor of medicine affiliated with the Duke Preparedness and Response Center at Duke University in Durham, North Carolina.

"Every Ebola patient in the [United States] and Europe, at least to my knowledge, has had at least two experimental therapies given simultaneously, so how you judge what provided the benefit is very challenging," Dr Wolfe said. "I can't say for sure that the improvement in vascular leak wasn't simply standard for someone who was improving at this point."

Vascular leak symptoms seemed to improve after treatment with FX06, Dr Wolfe explained. This improvement, however, coincided with decreasing viral load and the appearance of Ebola virus–specific antibodies, suggesting the patient was already mounting an immunologic response when he received FX06.

One way of parsing things out is to look at the mechanism of action, Dr Wolfe suggested. Favipiravir is an antiviral directed against the infection itself, whereas FX06 was designed to counteract the vascular complications resulting from the virus. All the other experimental products used so far are antiviral drugs or antibodies from survivors that directly target the virus itself, he continued.

"FX06 presents a novel way of tackling Ebola, since it is aimed solely at treating the complication of fluid leakage," Dr Wolfe stated.

Dr Wolfe commends the care team in their heroic efforts to help this patient survive.

"The capacity to deliver care is very different when using the infection control guidelines that we all have to use [for Ebola]," Dr Wolfe said. Auscultating the chest, inserting arterial and central lines, and intubation are all complicated by having to wear personal protective equipment. For example, because triple gloving interferes with palpation of pulses, the team resorted to ultrasound guidance to insert arterial and central lines.

"To get a guy who's this sick through his hospital stay is phenomenal," Dr Wolfe emphasized, "This case study not only builds on the published experience of the intensive care management of Ebola but helps with considerations of how to set up a hospital to be capable of handling such a patient."

FX06 is available on short notice in the United States for compassionate use from Bachem. An emergency kit has been sent to University Hospital Frankfurt for use as rapid supply stock in Europe.

The researchers presented an abbreviated description of the surviving case patient in a news conference in November.

The authors and Dr Wolfe have disclosed no relevant financial relationships.

Lancet. Published online December 19, 2014. Full text


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