The regulatory path for blood substitution products is paved with good intentions yet most of the companies in this sector are plenty familiar with the multitude of roadblocks along the way.

But every now and then one of the companies in this sector sees some progress, either clinically or financially. This week that company is Synthetic Blood International (Costa Mesa, California), which reported positive data from a statistical analysis of its Phase IIa study with Oxycyte in patients with traumatic brain injury — which is quickly becoming known as the "signature wound" of soldiers in Iraq and Afghanistan.

In line with preliminary study results the company reported in December, the company said statistical results confirmed that the primary endpoint of increasing patients' oxygen tension levels compared with baseline was met. Data also show a decrease in patient glucose and lactate/pyruvate (LP) ratio, consistent with increased glucose metabolism. Patients in the trial were stabilized with either 50% or 100% oxygen. Data determined that results of both treatment arms were favorable, with statistically significant differences in some data between the two treatment arms, according to Synthetic Blood International.

"This analysis further validates our initial study findings that Oxycyte is more effective in increasing brain oxygen tension levels and impacting other brain chemistries that contribute to more favorable clinical outcomes in patients with traumatic brain injury, than breathing either 100% or 50% oxygen alone," said Robert Nicora, president/CEO of Synthetic Blood. "Based on these positive results, we are working with Virginia Commonwealth University (VCU; Richmond, Virginia) to develop a protocol for a multi-center, controlled Phase IIb trial that could enroll up to 100 patients with traumatic brain injury."

Nicora told Medical Device Daily that commercially, Oxycyte could end up being a "blockbuster" product for the company if eventually approved.

"There's a huge unmet need for products like this in treating ischemic conditions such as traumatic brain injury for example," Nicora said.

Other ischemic indications for blood substitution products could include heart attacks or strokes, Nicora added.

Synthetic Blood hopes to begin its Phase IIb trial with Oxycyte sometime this year, Nicora told MDD, but he said the next big step for the company would be securing significant funding for the trial.

"We continue active discussions with several sources for financing the company," he said. "If we are successful in these discussions, the receipt of additional funding will enable us to move forward with our Phase IIb program and other development activities with Oxycyte, which include plans to initiate a cardiac ischemia study in an animal model."

The company also is in discussions with potential pharmaceutical partners — one which he described as "extremely large" and another "midsize" company — though Nicora could not disclose any details about those talks.

In this open-label, Phase II proof-of-concept, eight-patient study conducted at VCU, Oxycyte was administered to patients with severe traumatic brain injury and a Glasgow Coma Scale score of 3-9. The study protocol includes two groups. The first four study patients were stabilized with 50% oxygen for four hours before and 12 hours following Oxycyte administration. The remaining four study patients breathed 100% oxygen on the same schedule. Clinical data on brain oxygen and metabolite levels are compared in patients from both groups.

The primary purpose of this study is to demonstrate Oxycyte's ability to increase brain oxygen tension and favorably affect other brain chemistries that impact clinical outcome in patients suffering severe head injury. Additionally, the company noted, the study will further assess the safety of Oxycyte when given by intravenous infusion.

Due to a technical malfunction whereby a complete measurement of oxygen levels in the brain of one treated patient was not made, nine patients were treated during this study to meet the eight-patient enrollment goal, the company said. While survival was not a trial endpoint, seven patients in the trial survived their brain trauma.

Synthetic Blood said neither of the two mortality cases was related to the safety of Oxycyte. One patient suffered massive injury and was not expected to survive. Another patient was withdrawn from the trial upon the voluntary decision to remove life-support.

Not only could these early trial results mean big things for the company in the future, Nicora said the use of Oxycyte to treat conditions like traumatic brain injury could be widely beneficial for both civilian patients and injured soldiers.

Nicora said he has heard as many as 50% of the soldiers coming home from battle have some degree of brain injury and often the problem is not recognized until it's too late and the damage is permanent.

Synthetic Blood is not alone in this market.

The front-runners in the sector are Northfield Laboratories (Evanston, Illinois) and Biopure (Cambridge, Massachusetts), but they have both run up against significant hurdles to product approval. Another company in the area is Sangart (San Diego), which raised $50 million in a Series F round of financing last month. The financing included warrants that would add $50 million more in funding to the company (Medical Device Daily, April 6, 2007).

Shares of Northfield, however, lost more than half their value in December when it reported that its product, PolyHeme, failed to meet its primary endpoints in a Phase III trauma study. PolyHeme, a human hemoglobin-based oxygen-carrying red blood cell substitute, was being evaluated in severely injured and bleeding patients when a blood transfusion is needed but blood is not immediately available. The company said it still intends to file a biologic license application, based on certain non-inferiority data (MDD, Dec. 21, 2006).

Northfield's news came on the heels of Biopure's failure to win approval for a Phase III trial of its bovine-based oxygen therapeutic, Hemopure, for pre-hospital treatment of hemorrhagic shock resulting from traumatic injury (MDD, Dec. 17/Dec. 18, 2006).

Among others facing difficulty in the sector are Alliance Pharmaceutical (Evanston, Illinois), which has had clinical and financing trouble with development of Oxygent, an oxygen "carrier;" and Hemosol (Toronto), which went bankrupt in its attempt to develop Hemolink (MDD, Nov. 28, 2005).

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