The development of a viable substitute for blood has been one of the rockiest of roads, its speed bumps and potholes consisting of significant trial difficulties and the very complex nature of blood itself. Clearly, yet to be determined is whether the road is simply very long or ultimately a dead end.

Providing yet another example of the sector’s difficulties is ongoing criticism of Northfield Laboratories (Evanston, Illinois), most recently in the use of its oxygen therapeutic Hemopure. The company last month once again had to provide a defense of its trial for use of Hemopure for victims of trauma in response to a critical article by the Wall Street Journal. The article reported continuing critical statements by Senator Charles Grassley (R- Iowa), together with an alert about “urgent ethical concerns” about the trial sent to the FDA by the Office for Human Research Protections.

The WSJ story focused primarily on two issues: the study’s reliance on a waiver of informed consent by patients, with Grassley saying he was concerned that these patients were not fully informed of its risks – primarily deaths in a previous trial conducted by the company; and the use of a blood substitute in a study when real blood is available.

In a statement responding to the article, Northfield said that it has “adhered scrupulously” to FDA regulations, issued in 1996, which allow a waiver of informed consent “when patients are in a life-threatening situation, when obtaining individual informed consent is impossible, and when current therapy is unproven or unsatisfactory.” It said that the rule holds true when “there is the potential for direct benefit to the patients enrolled, which FDA has interpreted to mean survival benefit. Our study meets these criteria.” The company cited two “life-saving” benefits of this approach: the ability to provide oxygen-carrying fluid to a severely injured patient immediately at the scene of injury, and the avoidance of the use of blood in “the early hospital period.” Northfield also acknowledged the availability of blood once the patient arrives at a hospital but said this “may not be the optimal treatment for the early care of trauma,” based on the risks inherent in donated blood.

Northfield backed its discussion of the safety of the trial by noting reviews and approvals by its Independent Data Monitoring Committee (IDMC) and said that group “recently reiterated its recommendation to complete the trial based on four separate reviews of mortality and adverse event data from the first 500 patients enrolled.” And it said the IDMC stated: “As has been reported to Northfield Laboratories regarding the final assessment of the interim data, including 500 randomized patients, there were no statistically significant trends or safety issues identified to warrant modification or other changes in the current protocol and patient recruitment.”

The company also reported that while informed consent is often not obtainable from injured patients, the protocol provides clear guidelines for attempting to contact family members – from every 20 minutes for the first two hours after treatment to once a week “through day 30, if not previously accomplished.”

The WSJ also reported that two hospitals participating in the study using Northfield’s blood substitute product Polyheme have suspended further enrollment. Responding to that, Northfield said that “a few sites” have suspended trial enrollment to review “their activities” and that “three are once again enrolling.”

Northfield had to respond to comments made by Grassley – also reported primarily by the WSJ, which was critical of the company’s handling of a trial using PolyHeme in to treat abdominal aortic aneurysm, in which two of 81 patients died within a week of receiving the product. That story said that the company had “quietly shut down the trial and made no attempt to publicly disclose the results.”

The company responded to that attack, claiming that the newspaper report had contained several errors of fact that and that it had made no attempt to hide the results. Steven Gould, MD, CEO and chairman of Northfield, at the time said that three publications reported on the study, that the patients in the trial were highly complex and that the deaths were most likely the result of fluid management issues rather than any “pharmacologic effect” of Polyheme. Also at the time, an FDA spokeswoman defended the trial, noting the critical need for a blood substitute for survival, “particularly in emergency and battlefield situations.”

Novoste completes sale of VBT business

Novoste (Norcross, Georgia) officially exited the vascular brachytherapy (VBT) business last month, with another company assuming it as part of its broader brachytherapy line. Best Vascular (Springfield, Virginia) acquired substantially all of Novoste’s VBT business through the assumption of various Novoste liabilities related to the VBT business.

Krish Suthanthiran, president of Best, said the acquisition “fits our strategy of providing brachytherapy therapy products across a wide variety of clinical applications. It is of utmost importance that radiation therapy is available to cardiologists and their patients.” He added: “The Novoste system is the only remaining vascular brachytherapy product on the market, and having previously supplied Cordis (Miami Lakes, Florida), a Johnson & Johnson (New Brunswick, New Jersey) company, with VBT products, we believe we have the capability to assure the continuation of this important therapy in the cardiology market.” He added: “We remain committed to our radiation oncology customer base and look forward to serving the particular needs of the cardiology community with a therapy that has proven durable results.”

Best formally launched its marketing of the Novoste BetaCath product at a breakfast meeting at the Hyatt Regency Crystal City (Arlington, Virginia), in conjunction with the Cardiovascular Revascularization Therapies (CRT) meeting.

Al Novak, president and CEO of Novoste, termed the sale to Best “in the best interests of our shareholders by allowing Novoste to be free of its major liabilities associated with the VBT business.”

Best Vascular was established by Best Medical (also Springfield) for the purpose of focusing on the VBT acquired from Novoste. Best Medical is known for its radiation seed products utilizing several different isotopes. The company also has a complete line of catheters, needles, templates and accessories, including custom-designed products. Best Medical says it develops “new ideas” in brachytherapy, including VBT, and is a leader in the provision of radiation seeds for use by urologists in the treatment of prostate cancer.

The deal provides closure to what has been a rocky journey. The sale originally was contingent on a merger between Novoste and ONI Medical Systems (Wilmington, Massachusetts), which fell through last September after Novoste’s shareholders failed to approve the issuance of shares of Novoste common stock required to complete the merger.

Orasure ‘encouraged’ by home trial plans

What happens if a person uses a home test kit to determine if he or she has the HIV virus and the result is an indication of infection? Has the person used the test kit correctly so as to get a correct result? Will the person’s next steps be a rational follow-up or will the result produce an irrational response, even hysteria?

These are the questions that will be answered with new trials by OraSure Technologies (Bethlehem, Pennsylvania), which is seeking to win over-the-counter approval of its Advance Rapid HIV-1/2 Antibody Test, following recommendations by the Blood Products Advisory Committee (BPAC) of the FDA, during its meeting last month. The BPAC meeting included a discussion of the proposed studies and testimony from a variety of groups supporting the OTC approval for home use.

In a conference call following the meeting, Doug Michaels, president of Orasure, said he was “extremely encouraged” by the discussion and recommendations of the committee and that its feedback was “extremely valuable.” He also noted “unequivocal support from the public health and hospital community.”

Because the test for HIV infection is already FDA-approved as a prescription product, the company, he noted, does not need to do a Phase I trial but that it “will move directly to Phase II studies.” This will involve, Michaels said, “untrained users, focused primarily on the understanding of the materials provided with the product to evaluate the untrained users’ ability to properly collect the specimen, perform the test and interpret the test results.” The FDA, he noted, proposed three levels of test interpretation studies: “self testing, testing with simulated results . . . and contrived devices, put in front of the untrained user – negative, low positive and strongly reactive specimen.” The third phase, he said, will involve “assessment of the information provided in the kit, the clarity of that information, . . . testing the user’s understanding of how they can best be connected to care and, maybe, a post-market surveillance component.”

Michaels said that what the FDA committee had recommended was “by and large what we anticipated would be required to design our clinical studies originally. He noted that a key element of these efforts will be services and counseling by telephone as ‘part of the packaging and instructions for use – who to get in touch with appropriate healthcare professionals.” He said that the company will proceed to meet with the FDA “as rapidly as possible” to develop trial specifics, with his prediction that the studies “will launch some time this summer, no later.”

Questioned about the potential barrier of additional costs for the studies, Michaels declined to see negatives in either. “We weren’t disappointed at all. The outcome of today was very much in line with our expectations.” He noted that the recommended studies were very similar to what the company had itself proposed last November. He also indicated there was no great delay in moving forward with the trial plan. He noted that the oral fluid form of the test was launched in late 2004, that the company then approached the FDA in June of last year “about the requirements for an OTC approval” and that it now had “pretty clear guidance in terms of a path forward. My experience is that this is pretty good for the FDA,” Michaels said. “In the general scheme of things it’s moving along pretty well.”

OraQuick Advance is the only FDA-approved and CLIA-waived rapid point-of-care test that can detect antibodies to both HIV-1 and HIV-2 in 20 minutes, using oral fluid, finger-stick or venipuncture whole blood or plasma specimens.