Northfield Laboratories Inc. said it received clearance from the FDA to proceed with a pivotal Phase III pre-hospital trial of PolyHeme, the company's oxygen-carrying blood substitute that is derived from human blood but has a longer shelf life.
And while the Evanston, Ill., company said it is excited about the pending trial, it acknowledged in a conference call that the study will be expensive and that it will need to raise additional funds to see the project through to final regulatory approval.
"This is a gratifying day for Northfield. The clinical trial we proposed is unprecedented in its scope, design and setting," said Steven Gould, chairman and CEO, during the conference call. "This favorable response represents a seminal achievement in our efforts to develop PolyHeme as the first blood substitute to be approved for use in urgent blood loss when blood is not immediately available."
Northfield now plans a 700-patient study comparing use of the blood substitute in pre-hospital emergency care - accident scenes and ambulances - to the use of saline solution.
"Nobody has done a trial of blood substitutes in the ambulance setting in the U.S.," Gould said.
He said Northfield plans to recruit 20 Level 1 trauma centers for the trial, each of which will take between a couple of months to more than six months to begin enrolling patients.
The primary endpoint of the pending trial will be an improvement in 30-day survival. Patients, who must be suffering from hemorrhagic shock resulting from extensive bloodletting, will be randomized to receive either PolyHeme or the standard therapy, which is a saline-based solution since ambulances do not carry blood. Severe head injuries will be excluded from the trial because of their high mortality rate.
The trial has an interesting twist, which may push the enrollment date in some areas closer to the six-month figure. Because the patients eligible for the study are unlikely to be able to provide consent - the traditional protocol for a clinical trial - due to the extent and nature of their injuries, the trial will be conducted under federal regulations that allow clinical research in emergency settings using an exception from the requirement for informed consent.
However, before enrollment under this special exception can begin in a given community, the company must provide public disclosure via various media outlets on the potential risks and benefits of PolyHeme.
A local Institutional Review Board will oversee clinical trials at each study site. The IRB is an independent body composed of medical, scientific and nonscientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of patients enrolled in clinical trials.
Because of the added time for trial enrollment and its ambitious scope, he said that the cost of the Phase III study is likely to be very high, in the range of $10 million to $15 million, but he said he remained optimistic that the trial could be completed within a year and that the product then could be submitted for FDA approval.
While Northfield has ambitious plans, it acknowledged during the conference call that it has enough cash only to maintain its existing operations through year-end. Gould said the company is open to all options for funding the PolyHeme trial, but noted that "time constraints are such that we are apt to get money from new investors" rather than a development partner. He also said that while his company has a relationship with the military for use of the product in a battlefield trauma setting, he did not think the military would be supporting this particular trial.
The company has had problems in the past with earning a U.S. approval for the product. In 2001, the FDA turned down the company's application for PolyHeme, citing concerns about the design of an earlier trial, which used historical models to compare effectiveness.
Gould, who took over as CEO for Northfield last July, said he has spent a lot of time reintroducing the "quiet company" to Wall Street. He said he believes that with this high-profile trial approval, the company has "woken up a bit" and he believes it will have a less-difficult time raising the funds needed for the trial's completion. "I think, to some extent, people were waiting to see if we were really going to pass this regulatory milestone of having the FDA agree to our proposal, since it was so new, so landmark."