Northfield Laboratories Reports Results of Pivotal Phase III Trauma StudyEVANSTON, Ill.--(BUSINESS WIRE)--May 23, 2007 - Northfield Laboratories, Inc. (NASDAQ: NFLD) reported today results of its pivotal Phase III trauma trial with PolyHeme(R), its human hemoglobin-based oxygen-carrying red blood cell substitute. The trial was designed to seek an indication for use in the treatment of life-threatening red blood cell loss when transfusion is required and red blood cells are not available, not for use interchangeably with blood. This indication addresses a critical, unmet medical need.
The primary efficacy endpoint of the study was a dual superiority-noninferiority assessment of mortality at 30 days after injury. The margin to assess noninferiority, using the upper limit of the confidence interval, was set at 7% more than control. In the primary Modified Intent to Treat population, the upper limit was 7.65%. In the As Treated population, the upper limit was 7.06%. In the Per Protocol population, the upper limit was 6.29%.
Day 30 mortality was also a primary safety endpoint. Further analysis of the mortality data indicates that the difference in mortality at 30 days between patients who received PolyHeme beginning at the scene and continuing for up to 12 hours following injury, and control patients who received the standard of care, including early blood, was not statistically significant.
"The results of this study are best understood in the context of bleeding patients who do not have early access to blood transfusion," said Steven A. Gould, M.D., Chairman and Chief Executive Officer. "47 million Americans live more than an hour away from a trauma center where blood is available. Mortality rates in that scenario would be considerably higher than those observed in the control patients in the urban setting of this trial, where transit times were relatively short. We believe that when our data are extrapolated to patients who need an oxygen carrier and have delayed access to blood, PolyHeme can play an important role in saving lives."
Northfield will hold a conference call today, Wednesday, May 23, 2007, at 8:30 a.m. EDT to discuss the results of the study. To participate in the call, investors may dial 866.770.7146 and reference the passcode 56877457. Investors may also access a live audio webcast at www.northfieldlabs.com; this will be archived for two weeks. A telephone replay will also be available for two weeks by dialing 888-286-8010 and entering the passcode 14789842.
The study protocol pre-specified multiple patient populations for analysis: the primary Modified Intent to Treat population (MITT); the As Treated population (AT); and the Per Protocol population (PP).
The primary efficacy endpoint of the study was a dual superiority-noninferiority assessment of mortality at 30 days after injury. A noninferiority endpoint requires the establishment of a relative margin around the control outcome. The margin to assess noninferiority in this study, using the upper limit of the confidence interval, was set at 7% more than control.
The MITT population is comprised of all 714 patients both randomized and treated. In this population, patients were analyzed as randomized, and not based on the actual treatment they received. There were 41 randomized patients in the study who received the incorrect treatment. Therefore, the 21 patients randomized to PolyHeme who did not receive any PolyHeme were analyzed in the PolyHeme group. Similarly, the 20 patients randomized to control who did receive PolyHeme were analyzed in the control group.
The AT population is also comprised of all 714 patients both randomized and treated. However, in this population all patients were analyzed according to the treatment they actually received. Therefore, all patients who did receive PolyHeme were analyzed in the PolyHeme group, and all patients who did not receive any PolyHeme were analyzed in the control group. Although the AT population was pre-specified for safety rather than efficacy, it provides a meaningful opportunity to assess mortality as well.
The PP population is comprised of the 586 patients both appropriately randomized and correctly treated. The PP population does not include 128 patients who had major protocol violations related to eligibility or treatment regimen. Since the PP patients were treated exactly as specified in the protocol, Northfield believes the PP population represents the clearest opportunity to assess a treatment effect.
In the primary MITT population, the upper limit of the confidence interval was 7.65%. In the AT population, the upper limit was 7.06%. In the PP population, the upper limit was 6.29%. The data are shown in Table 1. -0-
TABLE 1 DAY 30 MORTALITY PolyHeme Control Upper Limit (deaths/N) % (deaths/N) % ------------------------- ---------- ----- ---------- ---- ----------- MITT 47/350 13.4 35/364 9.6 7.65% ------------------------- ---------- ----- ---------- ---- ----------- AT 46/349 13.2 36/365 9.9 7.06% ------------------------- ---------- ----- ---------- ---- ----------- PP 31/279 11.1 28/307 9.1 6.29% ------------------------- ---------- ----- ---------- ---- -----------
Secondary efficacy endpoints of the study included Day 1 mortality (Table 2), the incidence of multiple organ failure, the use of donated blood through Day 1, and an analysis of mortality by the mechanism of injury (blunt versus penetrating trauma). The incidence of transfusion of donated blood was significantly lower in the PolyHeme group at 41% than the control group at 51% (p(less than or =)0.05). There was no statistically significant difference between PolyHeme and control patients for the other efficacy endpoints. -0-
TABLE 2 DAY 1 MORTALITY PolyHeme Control (deaths/N) % (deaths/N) % ------------------------------------- ---------- ---- ---------- ---- MITT 34/350 9.7 27/364 7.4 ------------------------------------- ---------- ---- ---------- ---- AT 33/349 9.5 28/365 7.7 ------------------------------------- ---------- ---- ---------- ---- PP 20/279 7.2 21/307 6.8 ------------------------------------- ---------- ---- ---------- ----
The primary safety endpoints in the study were Day 1 mortality, Day 30 mortality, and durable serious adverse events (SAEs). Durable serious adverse events were prospectively defined as SAEs which resulted in a "permanently disabling" outcome. There were two durable SAEs in each group. There was no statistically significant difference between the PolyHeme and control groups for any of these endpoints.
Additional Safety Data
All adverse events (AEs), serious adverse events (SAEs), cardiac SAEs, and myocardial infarction (MI) were also analyzed. The overall incidence of AEs in the PolyHeme group of 93% (324 patients) was higher than that in the control group of 88% (322 patients), (p(less than or =)0.05). The most common AEs in both groups were: anemia, fever, and electrolyte imbalances. The overall incidence of SAEs in the study was 40% (141 patients) in the PolyHeme group and 35% (126 patients) in the control group (pgreater than or 0.05). The most common SAEs in both groups were: shock, pneumonia, and respiratory failure.
The incidence of cardiac AEs was 35% (123 patients) in the PolyHeme group and 29% (105 patients) in the control group (pgreater than0.05). The incidence of cardiac SAEs was 7% (23 patients) in the PolyHeme group and 4% (16 patients) in control (pgreater than0.05). The overall incidence of MI in the study as reported by investigators was 2%: eleven PolyHeme patients and three control patients (p(less than or =)0.05). Three PolyHeme patients and one control patient died.
The medical literature documents the difficulty of making an accurate diagnosis of MI in trauma patients for multiple reasons, including direct trauma to the chest. Myocardial infarction and myocardial ischemia are traditionally assessed by EKGs and the cardiac enzymes Troponin I and CK-MB, both of which can be altered by direct trauma. Approximately 75% of the patients in this study had abnormal EKGs or elevated cardiac enzymes. Because of the disparity between the low number of reported MIs and the high incidence of abnormal EKGs and elevated cardiac enzymes, Northfield has established an independent panel of cardiac experts to review the cardiac profiles of all 720 randomized patients in a blinded fashion to categorize MIs in the study.
"This was a seminal study. This summary represents our initial opportunity to explore the data on safety and efficacy in detail. We continue to believe there is a potential benefit to using PolyHeme in patients with delayed access to blood, whose expected mortality without oxygen-carrying replacement would be considerably greater," said Dr. Gould.
As the data have not been submitted to FDA, Northfield is preparing a detailed summary of the study data for submission to FDA for review.
About the Study
This randomized, controlled open-label, multi-center, active control pivotal Phase III study of 720 patients was designed to evaluate the safety and efficacy of PolyHeme when used to treat patients in hemorrhagic shock following traumatic injuries beginning in the prehospital setting. Treatment began at the scene of injury, continued in the ambulance during transport, and for up to 12 hours post-injury or a total of 6 units. Patients then received donated blood if they continued to bleed. Patients in the control group received the standard of care: saline in the field and during transport, followed by blood upon arrival at the hospital. Thirty-two Level I trauma centers participated in the study, which was conducted to seek an indication for the use of PolyHeme that addresses a critical, unmet medical need: the unavailability of blood.
In December 2006, Northfield announced that it had received the preliminary draft top-line data from its contract research organization. Northfield indicated that due to certain discrepancies in the data identified during its initial review, it became necessary to resolve the discrepancies and unlock the study database to make any necessary corrections. The process has now been completed, the study database relocked, and the data reanalyzed. Northfield has also had the opportunity to further analyze the study data, including additional safety data. These data have not been submitted to or reviewed by FDA.
About Northfield Laboratories
Northfield Laboratories, Inc., is a leader in developing an oxygen-carrying red blood cell substitute for the treatment of life-threatening blood loss, when an oxygen-carrying fluid is required and red blood cells are not available. PolyHeme(R) is a solution of chemically modified human hemoglobin that requires no cross matching and is, therefore, compatible with all blood types. It has a shelf life in excess of 12 months. For further information, visit www.northfieldlabs.com.
Forward Looking Statement
This press release may contain forward-looking statements concerning, among other things, Northfield's future business plans and strategies and clinical and regulatory developments affecting our PolyHeme red blood cell substitute product. These forward-looking statements are identified by the use of such terms as "intends," "expects," "plans," "estimates," "anticipates," "should," "believes" and similar terms. These forward-looking statements involve inherent risks and uncertainties. Our actual results may therefore differ materially from those predicted by the forward-looking statements because of various factors and possible events, including the possibility that since the data from our Phase III clinical trial have not been submitted to, or reviewed by, FDA, they may not be sufficient to demonstrate the safety or effectiveness of PolyHeme, our ability to obtain FDA approval to market PolyHeme commercially, our ability to obtain priority review, the availability of capital to finance our clinical trials and ongoing business operations, our ability to obtain adequate supplies of raw materials and to manufacture PolyHeme in commercial quantities, our ability to market PolyHeme successfully, the possibility that competitors will develop products that will render PolyHeme obsolete or non-competitive, our ability to protect our intellectual property rights, the outcome of certain governmental inquiries and purported class action lawsuit as described in our most recently filed annual report on Form 10-K and quarterly report on Form 10-Q, the possibility that we may be subject to product liability claims and other legal actions, our dependency on a limited number of key personnel, the uncertainty of third party reimbursement for our product and other risks and uncertainties described from time to time in our periodic reports filed with the Securities and Exchange Commission, including our most recently filed annual report on Form 10-K and quarterly report on Form 10-Q. These forward-looking statements speak only as of the date of this press release. We do not undertake any obligation to update or publicly release any revisions to forward-looking statements to reflect events, circumstances or changes in expectations after the time such statement is made. All subsequent written and oral forward-looking statements attributable to Northfield or any person acting on our behalf are qualified by this cautionary statement.
Posted: May 2007