Updated from 6:59 a.m. ESTI've received a good bit of email lately asking my opinion on Northfield Laboratories ( NFLD) and its experimental human blood substitute Polyheme. The interest in Northfield was sparked by the company's Dec. 20 announcement that the FDA would review Polyheme for approval with a decision date set for April 30. Northfield shares jumped from about 40 cents prior to the FDA announcement to more than $1. The stock closed Wednesday's trading session down 5.8% at 98 cents. Clearly, there's a contingent of retail investors out there who believe that the FDA, by accepting the Polyheme application for review, is signaling a willingness to approve the blood substitute despite its checkered history. I wouldn't make that assumption at all. In fact, Polyheme has very little chance of being approved, in my opinion. This is not a stock I'd chase. Northfield is trying to win a race to get the first human blood substitute approved where other companies like Biopure ( BPUR) and Baxter ( BAX) have failed previously. It's been two years since Northfield first announced the failure of the phase III Polyheme study, but recall that the death rate for trauma patients treated with Polyheme was over 13% compared to a death rate of just under 10% for patients treated with saline and blood. Scarier was the study's safety data, which went against Polyheme in every way measured. Patients treated with Polyheme reported more serious adverse events, more heart attacks and greater risks to the kidneys than the control patients. Polyheme's fans tend to ignore the blood sub's dangerous safety profile and rationalize an FDA approval on the belief that Polyheme is the only thing that can save the life of a severely injured and bleeding patient when blood is not available.
Perhaps, but the FDA is not going to approve a blood substitute, or any drug for that matter, when it's not safe, regardless of its life-saving potential. (Which in the case of Polyheme is not proven because the phase III study failed.) In the two years since the pivotal Polyheme data was released, Northfield has spent a lot of time and money to massage the data and reinterpret it in a way that puts Polyheme in a better light. Post-hoc analyses were done in which some patients were stripped from the data set, the safety data has been probed and "cleaned up," the data presented at medical meetings and most recently published this month in the Journal of the American College of Surgeons. I think these efforts have been a waste of time. Last April, Dr. Charles Natanson, a researcher at the National Institutes of Health, published a meta-analysis of blood substitutes, including Polyheme, which concluded that use of these products is associated with an increased risk of death and heart attack. Natanson's study was published in the Journal of the American Medical Association (JAMA), and uses data compiled from all previously conducted studies of human blood substitutes, including those from Northfield Labs. The FDA is taking the Natanson study and his finding that blood substitutes are not safe very seriously. At a two-day conference on blood substitutes sponsored by the FDA and NIH last April, the Natanson data were put under the microscope by a host of blood transfusion and trauma experts, but his conclusions were not seriously rebutted. In fact, FDA officials, including those at the agency who oversee the review of blood subs like Polyheme, went on record questioning their safety. If you haven't read the 700-page transcript from this two-day blood substitute meeting, I suggest you do before thinking about investing in Northfield.
If you read the transcript, you'll realize that there is very little support for Polyheme or any first-generation blood sub because of serious questions about safety. That includes situations where patients are at risk for death due to the unavailability of blood.
Polyheme, by the way, has never been studied in such a situation. Take special note of comments made by Dr. Tom Fleming, a noted bio-statistician, who completely dismantles Northfield's argument for using a "per protocol" analysis of the Polyheme data as a truer gauge of the blood sub's efficacy and safety. Fleming's comments can be found in the transcript of the April 29 meeting, starting on page 292. The FDA is likely to hold an advisory committee meeting to discuss and review the Polyheme application before the April 30 decision date nears. My bet: The meeting will not go well for Northfield, which will give FDA all the public ammunition it needs to reject Polyheme. Not that the agency really needs any new reasons to reject Polyheme, but a rebuke from an advisory committee will make it easier. One more note to seal Polyheme's fate: Dr. Sydney Wolfe is listed as a co-author on Natanson's JAMA paper regarding the safety risks of blood substitutes. Wolfe works for Public Citizen and is an outspoken critic of drug safety. More important, the FDA recently appointed Wolfe a permanent member of the FDA Drug Safety and Risk Management Committee. This FDA drug safety committee is certain to get involved in the Polyheme review. As the co-author of a paper that concludes blood subs, including Polyheme, to be unsafe, Wolfe is likely to take an active role against Polyheme's approval. Northfield shares closed Thursday down 22.2% to 77 cents.