A Medical Device Daily

The Securities and Exchange Commission (SEC) has begun an investigation into the clinical development of embattled Northfield Laboratories ' (Evanston, Illinois) blood substitute Polyheme. In a statement, the company said it will comply.

PolyHeme is a chemically modified human hemoglobin that requires no cross matching and is therefore compatible with all blood types. The substance has been experimentally used on trauma patients at several hospitals around the country without patient consent.

Northfield said in a statement that it had received an informal request to “voluntarily provide“ certain information to the staff of the SEC, adding that it intends to respond to the request.

Public concerns about the safety of the blood substitute arose after a Feb. 22 report in The Wall Street Journal.

The WSJ article, headlined “Amid Alarm Bells, Blood Substitute Keeps Pumping,“ said about 12% (10) of patients on the product in an abdominal aorta aneurysm trial suffered heart attacks and two out of 81 patients died within seven days of receiving PolyHeme. None of the 71 patients in the trial who received real blood had heart attacks, the paper said, adding that the trial results were intentionally never published.

The article charged that the company “quietly shut down the trial and didn't publicly disclose the results.“

The trial also suggested that PolyHeme was linked to other serious adverse events such as heart rhythm aberrations and pneumonia, the paper said. These events occurred in 54% of the PolyHeme patients vs. 28% in the control group, the article added.

In an earlier statement, the company said the WSJ article contained several errors of fact and misinterprets the Acute Normovolemic Hemodilution (ANH) – described in the article as the abdominal aorta aneurysm – clinical trial protocol and results.

The company said it particularly disagrees with the characterization that Northfield did not disclose the results of the trial or discouraged others from publishing its results. In fact, it said it believes that prompt publication of all the study data would have been favorable to the company.

“We made no effort to discourage the publication of ANH data and in fact, three publications have resulted from the study, with the fourth expected soon,“ said Steven Gould, MD, chairman and CEO of Northfield, in a statement. “We believe that publishing the full data upon closing the study would have shown that PolyHeme could not be isolated as the cause of the observed serious adverse events.“

The company said the ANH trial was conducted in the late 1990s and was a complex study involving a difficult and unusual procedure in a high-risk population from whom individual consent was obtained.

The company also said that periodic reviews by an independent monitor have deemed the trauma study fit to continue.

Northfield has also said it believes that heart attacks in the ANH trial may have been caused by excessive fluid volume delivered to the PolyHeme patients.

The FDA has said this explanation is plausible and okayed the ongoing study of the use of PolyHeme in trauma patients.

Senate Finance Committee chairman Sen. Charles Grassley (R-Iowa) has been critical of the trial design for PolyHeme.

Grassley, who has been an outspoken critic of the FDA, which cleared the trial for use of PolyHeme in trauma patients in 2003 (Medical Device Daily, March 7, 2003) that waives an informed consent requirement – provided the trial is accompanied by a community outreach program – pressed the agency for details on its role in the clinical trial of the blood substitute being tested on patients in 18 states.

Grassley, whose panel has oversight of Medicare and Medicaid programs, has requested that the FDA make a full public disclosure about the PolyHeme clinical trial to his committee.

“It is outrageous that, for all intents and purposes, the FDA allowed a clinical trial to proceed, which makes every citizen in the United States a potential 'guinea pig' without providing a practical, informative warning to the public,“ the Iowa Republican said in a letter to acting FDA Commissioner Andrew von Eschenbach.

In his letter to the FDA, Grassley expressed concern that patients could be subjected to the experimental blood product unless they were wearing a wristband that says they decline to participate in the study.

Many people probably do not know how to get the wristband, he added. “Why should Americans have to wear a bracelet at all times to protect themselves from a government-sanctioned medical experiment if they happen to get into a car accident?“

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