In light of last week's news that blood substitutes have led to a 30% increase in the risk of death and a nearly threefold chance of having a heart attack, Synthetic Blood International (SBI; Costa Mesa, California) has reiterated that its Oxycyte is not a synthetic blood and is not hemoglobin-based.

Despite the company's name, its flagship product Oxycyte is being developed as a therapeutic oxygen carrier, with application first as a treatment for traumatic brain injury and, if found to be successful, a slew of other potential indications down the road.

"Initially when the company was founded, the focus was on developing a blood substitute," SBI President Dick Kiral told Medical Device Daily. "But a few years back, we really changed the strategic direction to focus on oxygen delivery."

Highlighting the change in strategy, SBI has asked shareholders to approve a name change at a shareholder meeting scheduled for June 17. The proposed new name is Oxygen Biotherapeutics.

SBI's clarifications were prompted by an analysis of a number of hemoglobin-based oxygen carrier (HBOC) trials by the Journal of the American Medical Association, which pointed out that there is a "clinically important increase in risk of mortality and risk of myocardial infarction across HBOC trials" and that "more troubling, trials continue to be planned and conducted in the presence of accumulating knowledge as demonstrated by the cumulative meta-analyses."

The FDA and National Institutes of Health also held a workshop last week on HBOCs, during which the JAMA findings were center stage. Authors of that study suggest that no further Phase III studies be conducted with HBOCs, given the known toxicities.

"Until the mechanisms and potential toxicities of HBOC products are better understood, patients cannot be placed at unacceptable risk," wrote lead study author Charles Natanson, MD, of the critical-care medicine department in the NIH Clinical Center.

"I just came back from the HBOCs meeting in Bethesda," Kiral said. "There seems to be some safety issues and cardiovascular events reported. The FDA will publish a paper looking at the whole thing overall. But the tone of the meeting was don't treat all HBOCs alike,' in response to the fact that JAMA grouped findings about various products."

Although Oxycyte could be used as a blood substitute, Kiral said it's a therapeutic oxygen carrier and is not hemoglobin-based. Instead, it's a synthetic perfluorocarbon (PFC) therapeutic oxygen-carrying intravenous emulsion that can carry five times more oxygen than hemoglobin, making it an effective means of transporting oxygen to tissues and carbon dioxide to the lungs for disposal.

Because it is a PFC and not based on hemoglobin, it does not have the safety issues identified in the JAMA article, he said.

"We're using Oxycyte in a therapeutic way, focusing on traumatic brain injury," Kiral said. "We're not trying to replace blood. This allows us to enter a lot more markets, rather than just as a general blood substitute, which have a bad name overall because you're not really replacing all the functionality of the lost blood. You replace volume and oxygen, but none of the clotting factors are replaced."

Last May, SBI reported results from a Phase IIa pilot trial of Oxycyte in human isolated closed-head injuries, which was conducted at the Virginia Commonwealth University Reanimation Engineering Shock Center (Richmond, Virginia). Nine patients received a single dose of Oxycyte within four to 12 hours after entering the hospital. Data collected from these patients mirrored what was found in earlier animal experiments, and patient outcomes were dramatically better than expected, as compared to historical controls (MDD; May 17, 2007).

Current treatments for these kinds of head injuries involve supportive care, surgical drainage of blood from inside the skull, and the administration of added oxygen through the lungs. But nothing is available to improve oxygen delivery to the brain tissues that are starving for oxygen and dying. SBI is trying to fill that niche.

Kiral said SBI filed an application with the FDA for a Phase IIb/III trial comparing Oxycyte with currently available therapy in up to 200 patients. It's intended to be a randomized, double-blind, and placebo-controlled trial at six major neurosurgery centers throughout the world. Discussions, briefings and a Department of Defense (DoD) grant have been submitted for further investigations.

"We've been going back and forth with FDA, answering questions and dealing with the usual stumbling blocks," he said. "We're hoping, if everything goes well, we'll start that trial in early summer."

The U.S. Office of Naval Research has funded research related to the use of PFCs for the treatment and prevention of decompression sickness (DCS) over the last six years. DCS causes tissue damage when bubbles in the blood vessels block delivery of oxygen to the tissues. Oxycyte not only delivers the oxygen, but it helps to remove the bubbles. The program to develop Oxycyte as a treatment for DCS is a major component of the Navy's Disabled Submarine Initiative.

Kiral said the Navy will seek FDA approval for the use of PFCs in the treatment of DCS. About $6.5 million in DoD grants have been submitted and are under review.

Although SBI has adequate funding for the near term, with help provided via grants to the U.S. Navy and Army researchers, the company said it will be looking for additional funding in about a year and half to continue the development of Oxycyte.