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New England Journal of Medicine Publishes Promising Study Results of NovoSeven(R) Coagulation Factor VIIa (Recombinant) in Acute Intracerebral Hemorrhage

Key Findings Show in This Deadliest and Least Treatable Form of Stroke, NovoSeven Limited Hematoma Growth and Reduced Three-Month Mortality and Morbidity

Novo Nordisk Inc. today announced the results of a recently completed clinical trial of NovoSeven Coagulation Factor VIIa (Recombinant) in patients with acute intracerebral hemorrhage (ICH) as published in this week's New England Journal of Medicine (NEJM). The NEJM article, "Recombinant Activated Factor VII for Acute Intracerebral Hemorrhage," presents the results of the largest clinical trial ever conducted with a pharmacologic agent for the treatment of ICH. The study found a reduction in hematoma growth (bleeding in the brain), decreased mortality, and improvement in neurological and clinical outcomes in patients treated with NovoSeven compared to placebo.(1)

The preliminary results of this trial were initially presented at the Fifth World Stroke Congress in Vancouver, B.C., in June 2004, and most recently at the International Stroke Conference in New Orleans, LA, in February 2005.

"One of the strongest predictors of mortality and morbidity in ICH patients is hematoma volume and with the administration of NovoSeven hematoma growth was significantly limited," said Dr. Stephan Mayer, associate professor and director, Neurological Intensive Care Unit, Columbia University Medical Center and lead investigator of the study. "The current medical and surgical treatment options for ICH are not effective. Thirty-five to fifty percent of patients die within one month and if they survive, they are living with serious neurological deficits. The current data suggest a possible change in our paradigm for the treatment of ICH."

The trial results showed that treatment of ICH with rFVIIa within four hours of symptom onset reduced mortality and improved three-month clinical outcome, along with the reduction in hematoma growth, despite a greater frequency of thromboembolic events.(2)

The trial included 399 patients, all diagnosed by Computed Tomography Imaging (CT Scan) within 3 hours of ICH onset. Patients were randomly assigned to receive placebo (N=96), 40 (N=108), 80 (N=92), or 160 (N=103) µg/kg doses of rFVIIa within one hour of the baseline scan.(2)

The primary endpoint of the study was to determine if recombinant activated Factor VII (rFVIIa) could reduce hematoma growth after ICH. The primary outcome measure was the percent change in ICH volume at 24 hours. Clinical outcomes were assessed at 90 days.(2)

Key Findings Reported in the NEJM article include:

-- Primary endpoint: reduction in percent hematoma growth
   - ICH volume growth in the 40, 80, and 160 µg/kg treatment groups
     (P=0.01, rFVIIa vs. placebo) was 16%, 14%, and 11%, respectively
     (corresponding to a relative reduction of 45%, 52% and 62%)(2)
     compared to 29% in the placebo treatment group.

-- Secondary endpoint: Significant improvement in neurological and
   clinical outcome and decreased mortality and morbidity
   - Mortality was reduced by 38% for rFVIIa-treated patients compared
     to placebo-treated patients (P=0.02).(2)
   - 69% of placebo-treated patients died or were severely disabled
     (modified Rankin Scale (mRS) score 4-6), compared to 53% of the
     rFVIIa-treated patients (P=0.004).(2)
     - Receiving rFVIIa more than doubled a patient's chances of
       improving one level on the mRS.(2)
     - This represents a 16% absolute reduction in the risk of death
       or severe disability at three months according to the mRS.(2)

-- Safety endpoint: The overall frequency of fatal or disabling
   thromboembolic serious adverse events did not differ between the
   rFVIIa (2%) and the placebo (2%) groups. However, arterial
   thromboembolic serious adverse events occurred statistically
   significantly more frequently with rFVIIa treatment (5%) than with
   placebo (0%), manifesting in the form of myocardial ischemic events
   and cerebral infarction. The majority of patients recovered from
   these complications.

"We are very encouraged by the positive data from this study for NovoSeven® in the treatment of ICH," said Michael Shalmi, M.D., MBA, vice president, biopharmaceuticals, Novo Nordisk Inc. "Patients suffering an ICH have not had any well-documented treatment options available. These results fuel our desire to further study the use of NovoSeven in ICH and other critical bleeding indications."

About NovoSeven

NovoSeven Coagulation Factor VIIa (Recombinant) is indicated for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX. NovoSeven is the only recombinant FVIIa for effective, reliable treatment of bleeding episodes in these patients. Its unique mechanism of action induces hemostasis independently of FVIII and FIX.

About ICH

Intracerebral Hemorrhage (ICH) is the deadliest and most disabling type of stroke.(3) ICH is bleeding within the brain, which can start spontaneously rather than from external factors such as head trauma. During ICH, blood accumulates in the brain, creating a reservoir of blood called a hematoma.(3,4) Larger hematomas are more likely to create permanent brain damage, which can cause severe permanent physical and mental disability, and in many cases death.(5,6) Fifteen percent of all stroke victims will be diagnosed with ICH in the U.S.(7) Mortality occurs in 35-52% of these patients within one month, and less than 20% of the survivors are likely to become functionally independent.(8)

Novo Nordisk is a healthcare company and a world leader in diabetes care. The company has the broadest diabetes product portfolio in the industry, including the most advanced products within the area of insulin delivery systems. In addition, Novo Nordisk has a leading position within areas such as hemostasis management, growth hormone therapy, and hormone therapy for women. Novo Nordisk manufactures and markets pharmaceutical products and services that make a significant difference to patients, the medical profession and society. With headquarters in Denmark, Novo Nordisk employs approximately 20,000 full-time employees in 69 countries, and markets its products in 179 countries. Novo Nordisk's B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol "NVO." For global information, visit www.novonordisk.com ; for United States information, visit www.novonordisk-us.com.

(1) Mayer, S. et al. Recombinant Activated Factor VII for Acute Intracerbral Hemorrhage, Manuscript

(2) Mayer, S. et al. Recombinant Activated Factor VII for Acute Intracerbral Hemorrhage, Manuscript

(3) "About Stroke: Intracerebral Hemorrhage," 19 Nov. 2004 http://www.strokecenter.org/pat/ich.htm.

(4) "Hematoma," 19 Nov. 2004 http://cancerweb.ncl.ac.uk/cgi-bin/omd?query=hematoma.

(5) ICH Backgrounder Document

(6) Mayer, S. et al. Recombinant Activated Factor VII for Acute Intracerbral Hemorrhage, Manuscript

(7) Mayer, S. et al. Recombinant Activated Factor VII for Acute Intracerbral Hemorrhage, Manuscript

(8) Broderick JP, Adams HP, Jr, Barsan W, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1999;30: 905.

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