The stock of Northfield Laboratories (Evanston, Illinois) jumped nearly 32% Monday after an independent data monitoring committee (IDMC) gave the go-ahead for the ongoing Phase III trial of PolyHeme.
The approval marks the first time that a hemoglobin-based oxygen therapeutic has surpassed the third planned interim analysis milestone without requests for modification to a trial in high-risk trauma patients. The committee's decision was based on blinded mortality data in the first 250 people enrolled.
"This is a validation of everything to date, and we are very gratified to have reached this point," said Steven Gould, chairman and CEO of Northfield.
Northfield's shares rose $3.78 Monday to close at $15.75.
The IDMC also performed a blinded power analysis to determine if an increase in the sample size was needed, based on a comparison of the predicted mortality rate with the mortality rate observed in the trial to date. The committee concluded that the original 720 patients planned for enrollment would be sufficient.
The Phase III study is designed to evaluate PolyHeme when administered to patients in hemorrhagic shock following traumatic injury. The primary endpoint is survival at 30 days, and patients are being enrolled at Level 1 trauma centers throughout the U.S.
"A hemoglobin-based oxygen therapeutic is being used for the first time in this country at the scene of injury," Gould told Medical Device Daily's sister publication, BioWorld Today. "That's what is so revolutionary about this trial."
PolyHeme is a solution of chemically modified hemoglobin that requires no cross matching and is compatible with all blood types. It has a shelf life of more than 12 months.
The FDA has never approved a blood substitute.
High-risk trauma patients typically need transfusions, but blood is not carried in ambulances. While saline solution is used to replace blood loss, it does not carry oxygen to the body's tissues. Thus, PolyHeme could act as a substitute in situations of life-threatening blood loss.
PolyHeme now has moved beyond the first three interim analyses conducted after 60, 120 and 250 patients were enrolled in the Phase III and followed for 30 days by the IDMC. The next evaluation will take place once 500 patients are enrolled.
The development of oxygen therapeutics, once called blood substitutes, has challenged several biotech companies.
With no precedent set, companies such as Biopure (Cambridge, Massachusetts), Hemosol (Toronto) and Alliance Pharmaceutical (San Diego), as well as Northfield, have found it difficult to meet the regulatory requirements for marketing a blood-like product that can deliver oxygen to tissues without toxicities.
Biopure has developed Hemopure in the clinic since the 1980s. It filed a biologics license application in 2002, but the FDA requested more work. Last week, the company completed enrolling patients undergoing elective coronary angioplasty in a Phase II European trial.
And while Hemosol put its product Hemolink on the shelf for now, Alliance continues to develop its product Oxygent for worldwide markets, despite some adverse event snags from an earlier Phase III cardiac surgery study.
Northfield puts the market for high-risk trauma patients at $500 million in the U.S.
Phase III enrollment of the 720 patients should be complete by the end of this year, and Northfield could file for approval in the U.S. sometime in 2006.
"Our focus, unlike all the other sponsors, has really been on trauma from the outset," Gould said.
Northfield intends to market the product alone in the U.S. and could expand the market from high-risk trauma to elective surgery or oncology. The worldwide market potential for PolyHeme is estimated at between $1 billion and $2 billion for all indications.
PolyHeme started out as a research project, funded by the Department of Defense and the U.S. Army, in the late 1960s. When the work produced a product that appeared to have clinical utility and commercial potential, Gould and four other scientists founded Northfield in 1985.
Northfield attempted to gain approval for PolyHeme in 2001 based on astounding Phase II data. In the trial, each patient received up to 20 units of PolyHeme within 20 minutes. The normal blood volume in humans is 10 units. A total of 40 patients had lost all of their own blood and were kept alive with circulating PolyHeme. The endpoint, like the Phase III trial, was survival at 30 days.
The Phase II trial, however, was conducted in trauma patients at the hospital setting. The FDA wanted another trial done at the scene of injury. Northfield started the Phase III trial in high-risk trauma patients two years ago last month.
In other news in this sector:
Synthetic Blood International (Costa Mesa, California) said that Virginia Commonwealth University Medical Center (Richmond, Virginia) received approval from its investigational review board (IRB) to open patient enrollment for its Phase II Oxycyte trial. Oxycyte is the company's perfluorocarbon blood substitute and therapeutic oxygen carrier.
Robert Nicora, Synthetic Blood president and CEO, said, "We have now opened two clinical sites where patients are actively being screened for enrollment." Additional sites are being reviewed for IRB approval, including two sites in Durham, North Carolina, and the University of South Florida's Tampa General Hospital, which conducts a large number of hip replacement surgeries.
The company said it expects that pooling from this large patient population will be an asset in advancing patient enrollment in the Phase II trial.