Thanks to an unprecedented number of blood donations across America in the wake of the World Trade Center and Pentagon attacks, U.S. blood reserves are in excellent shape--for now. But a blood shortage is still a real possibility as the military prepares for battles on foreign shores. Because donated blood must be kept refrigerated and goes bad after 42 days, it may not be available where it's most needed. "Blood isn't something you can easily get to where the [military] action is," says Dr. Jeffrey D. Kerby, a laboratory director at Wilford Hall Medical Center at Lackland Air Force Base in Texas.
For the past two decades, the quest to develop a blood substitute has been pursued by tiny biotech startups and Big Pharma alike. Finally, potential winners are breaking out of the pack. On Aug. 28, Northfield Laboratories Inc. in Evanston, Ill., became the first company to file for Food & Drug Administration approval. Its product, PolyHeme, is derived from human blood. A second company, Biopure Corp. in Cambridge, Mass., said it will file for approval of Hemopure, derived from cow's blood, by the end of the year. And Alliance Pharmaceutical Corp. in San Diego is in the late stages of testing a chemical blood substitute, Oxygent. These products, though different in makeup, have similar crucial attributes: They are compatible with any blood type and stay fresh for a year or more.
The technological effort that went into these products cannot be underestimated. Scientists have found it extremely hard to replicate the ability of red blood cells to ferry life-giving oxygen through the body. Some early blood substitutes worked in animals but proved toxic in humans. Even the blood substitutes being readied now are not meant to permanently replace the real thing. Artificial blood circulates only for a matter of hours, sustaining patients until they can replenish their own blood or get access to donated supplies.
TOUGH SELL. Still, artificial blood could save thousands of lives each year--provided it reaches the market. The three leading U.S. players are tiny, unprofitable, and need millions of dollars to ramp up production. Plus, the FDA is sure to be a tough critic. "This is not similar to any other product we've ever dealt with," says Dr. Abdu I. Alayash, who heads the FDA's program for blood research. "It's going to take a great deal of time and effort to understand."
Of the three contenders, Northfield is in the lead and is so sure that PolyHeme will pass muster with the FDA that it has applied for fast-track approval, which would guarantee it a decision within six months. The company extracts still-potent hemoglobin from outdated blood and chemically transforms it into a purified solution compatible with all blood types. Northfield is seeking approval to stop oxygen loss in traumas until the patient can receive real blood. "It would eliminate the time required to test for compatibility and give the doctor more time to find the source of the bleeding," says President Steven A. Gould.
Despite those seeming advantages, Northfield has found it tough to recruit trial participants--few patients in emergency situations care to volunteer. That leaves some experts wondering if the FDA will demand more data. "If you have an adverse reaction in 1 in 10,000 patients, that would be a concern," says Dr. Harvey G. Klein, chief of the National Institutes of Health's Transfusion Medicine Div. A small trial won't address that issue.
To reduce such hurdles, Northfield rival Biopure seeks approval for its Hemopure product only for use during orthopedic surgery, a much easier setting for recruiting volunteers. Hemopure is made by extracting hemoglobin from cow blood, then chemically modifying it in a 17-step process to make it compatible with humans. But Biopure must convince the FDA and the public that Hemopure won't transmit mad cow disease. The company uses only U.S.-bred cows and insists that its rigorous manufacturing method eliminates disease-causing agents. "We just need to get people to understand that," says CEO Carl W. Rausch.
If he fails, mad cow worries could take a slice out of an already limited market. Orthopedic surgery represents just 15% of the potential $12 billion market for blood substitutes, analysts say. But given that Hemopure can stay fresh for three years without refrigeration, it would be ideal for emergency settings. Biopure will keep researching such uses, but it's years away from having enough data to satisfy the FDA.
BIG LOSSES. Alliance is in a similar bind. In January, the company halted a late-stage trial of Oxygent when some patients undergoing cardiac surgery suffered strokes. Oxygent is a milky mixture of chemicals designed to carry oxygen through the body. The company says that it was the method by which the concoction was injected and not the product itself that was faulty. It also believes that preexisting conditions common to heart patients, such as obesity and diabetes, may have made the study subjects more prone to strokes. To be safe, Alliance designed a new trial that focuses only on elective, noncardiac surgery. "This needs to be tested in controlled, measurable settings, and that's hard to do in trauma," says Alliance CEO Duane J. Roth. The product won't be ready for FDA review until at least 2003.
All three companies are racing against time. Northfield has lost $5.4 million so far this year, and Biopure $29.4 million. Alliance, which is $31 million in the hole, will receive an $11 million infusion from marketing partner Baxter Healthcare Corp. this year but will have to scrape up considerably more if it wants to survive beyond 2002. "This sector has experienced spectacular failures, and that will make raising funds even more difficult," says CIBC World Markets analyst Steven B. Gerber. In other words, despite the hopes for substitutes, blood drives won't become a thing of the past. By Arlene Weintraub in Los Angeles