FDA Clears Firm for 20-Unit Level in Phase II Study in Trauma

    EVANSTON, Ill., Aug. 12 /PRNewswire/ -- The Food and Drug Administration
has asked Northfield Laboratories Inc. (Nasdaq: NFLD) to expand the number of
patients in Phase III clinical trials of its blood substitute, PolyHeme.
Although, Northfield's Phase III trials have progressed without negative
incident, the FDA based its request Tuesday on what it characterized as
public concern over failures of competing products in Phase III trials.
    At the same time, the FDA has cleared Northfield to infuse up to 20 units
of PolyHeme, essentially two times the blood volume of the average adult, in
continuing Phase II trials being conducted among trauma patients.
    "Although an expanded number of patients in our Phase III effort will
likely lead to delays in this important product's availability to patients, we
understand the FDA's concern regarding public perceptions of safety,
especially after unfortunate outcomes in competing research," said Richard
DeWoskin, Northfield's chairman and chief executive officer. "An expanded
study probably would delay completion of the Phase III trials into the late
spring of 1999."
    "PolyHeme has been infused in more than 100 patients over the past two
years without negative side effects and, in its Phase II trials, has replaced
the need for red cell transfusions on a one-to-one basis.  We believe these
results, and the Phase III trials completed to date, reflect the fundamental
safety and effectiveness the FDA is seeking in a product before its commercial
introduction," he continued.  "However, we also recognize that the public must
have complete confidence in each new medical treatment brought to market, and
we recognize the importance of reinforcing the public's awareness of how
PolyHeme differs from those products that failed."
    The protocol cleared earlier by the FDA includes 240 elective surgery
patients.  At present, Northfield and the FDA have agreed that at least 600
patients would need to participate in an expanded study, seeking to balance
the public's concern about blood substitute safety with the compelling need to
bring such a product to market.
    DeWoskin said the timing of the two developments reflects the contrast
between Northfield's own research and the external nature of public
perceptions.  It also reinforces the core science behind Northfield's product,
he added.
    The science behind PolyHeme is based on the insight that raw hemoglobin
can be toxic outside the red blood cell and that, in order to provide safe
transfusions of a blood substitute, it is necessary to make the hemoglobin
molecule larger than its natural state.  To do that, Northfield polymerizes
the hemoglobin molecule to create PolyHeme.  Some competing research efforts
have focused on the idea that the hemoglobin molecule breaks apart in some way
and that the smaller parts are the source of toxicity.  Other research efforts
have focused on ways to encapsulate the hemoglobin molecule, enabling it to
transfer oxygen from the lungs to the body's tissues without creating
toxicity.
    "Recent results in competing research leave Northfield as the only major
competitor in the search for a safe, effective blood substitute," DeWoskin
noted.  "At the same time, negative results in competing research seem to have
reduced public confidence in the ability of any company to achieve this
fundamental goal.  To the extent that a larger number of patients can help us
restore public confidence, it is critical that we address these concerns."
    Northfield Laboratories, a development stage company, received clearance
from the Food and Drug Administration in April 1997 to begin Phase III trials
of PolyHeme(TM).  The pivotal trials were the first Phase III study to include
direct replacement of blood in large volumes, and mark a milestone in
medicine's search for an oxygen carrying blood substitute, the company said
today.
    Under the Phase III protocol cleared by the FDA, Northfield has infused
surgical patients with up to six units of PolyHeme, Northfield's proprietary
blood substitute.  The six-unit level (3 liters containing 300 grams of
hemoglobin) represents approximately 60% of an adult's entire blood volume.
Northfield Laboratories is the only firm to report successful achievement of
this high dose level in any phase of clinical testing, and the only firm to
evaluate its oxygen carrier as a direct replacement for blood in high volumes
in a Phase III study.
    In trials leading up to the Phase III clearance, Northfield infused its
blood substitute in over 100 individuals, including infusions at an
unprecedented dose level of ten units, without ill effect.  This is equivalent
to the replacement of a patient's entire blood volume.  In studies of trauma
patients, PolyHeme replaced the need for donated blood on a one-to-one basis,
according to the company.
    In November, 1996, the company received clearance from the FDA to conduct
clinical trials of PolyHeme at the ten-unit level, which is equivalent to
replacing the total blood volume of an adult human being. This additional
study, separate from the Phase III trials, is the one being expanded to the
20-unit level.
    "Although the Phase III trial will continue at the six-unit level, we
believe this Phase II trial will provide important insights regarding use of
PolyHeme in situations requiring very large volumes of blood replacement,"
DeWoskin said.

    BACKGROUND
    Northfield Laboratories was founded in 1985 to provide a corporate entity
to commercialize the scientific developments of a research team specializing
in a hemoglobin-based blood substitute.  That research, including some of the
key officers of the company today, dates back to 1970.
    PolyHeme, Northfield's blood substitute, is a solution of polymerized
hemoglobin.  Hemoglobin, contained in the red blood cell, is the molecule that
carries and transfers oxygen throughout the body.  This oxygen-carrying
quality is essential to sustaining life.  Because the red cell includes most
of the factors that require blood typing and cross-matching, a blood
transfusion is, in reality, a tissue transplant and can create some rejection
response from the recipient.  Separated from the red cell, however, raw
hemoglobin is toxic to the kidneys and can cause vasoconstriction, a
tightening of the muscle wall surrounding a blood vessel.
    Although some research into blood substitutes has included other
materials, most studies have focused on harvesting and transfusing hemoglobin,
with varying degrees of success.  Northfield's research, and its patents,
focus on the need to polymerize hemoglobin as a means of maintaining its
oxygen carrying capability while eliminating its harmful side effects.
    PolyHeme is a solution of polymerized hemoglobin molecules, essentially
small chains of linked tetrameters.  In comparison with red cell transfusion,
it is believed PolyHeme offers the following benefits:
    Disease free:  Blood transfusion can transmit diseases, including viral
diseases such as AIDS and hepatitis and parasitic diseases including malaria
and trypanosomiasis.  The production process for PolyHeme kills these disease
organisms.   The same process cannot be applied to the blood itself, however,
as it would kill the blood cells along with the unwanted viruses and bacteria.
    Universal Compatibility: Because the cell tissue is removed from the
solution, no typing or cross-matching is required, eliminating transfusion
reactions and making PolyHeme a universal donor solution.
    Immediate Availability:  Because it does not require cross-matching or
other preparation steps, PolyHeme is immediately available for transfusion in
emergency situations.
    Extended Shelf Life: While human blood has a useful shelf life of 28-42
days, PolyHeme has a shelf life in excess of 12 months.
    In 1994, the company completed its initial public offering, raising funds
to continue its research, and returned to the market in 1995 to obtain
additional capital to bring PolyHeme to full commercial production.
    In 1996, Northfield Labs completed the first prospective, randomized,
large volume Phase II trauma trial, directly comparing the use of a blood
substitute to blood.  After having transfused patients at dosages up to six
units of PolyHeme, Northfield received FDA clearance to conduct an additional
Phase II trauma study at dosages up to ten units.
    Later in the year, the company entered into an agreement with Hemerica,
Inc., a subsidiary of Blood Centers of America, under which Hemerica would
supply Northfield with 82,500 units per year of packed red cells, the source
material for PolyHeme, at a price of $26 per unit, over a three-year period.
    In addition, Northfield and Hemerica agreed to a joint effort to increase
the amount of raw material available in excess of the contracted amount.  It
requires approximately two units of red cells to create one unit of PolyHeme,
according to the company.  Outdated red cells, unfit for transfusion, can be
used as a raw material for PolyHeme, however, giving these cells a "second
life" as a transfusion medium.
    Currently, the company is completing plans for a commercial-scale
production facility with a capacity of approximately 300,000 units of
PolyHeme.
    Northfield Laboratories was founded in 1985.  The Company is headquartered
in Evanston, Illinois, and its stock is traded on the Nasdaq National Market
System under the symbol NFLD.

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