Enzon Announces Schering-Plough Reports Results Of Clinical Studies Of PEG-INTRON And REBETOL Combination Therapy For Hepatitis C At Digestive Disease Week Meeting.

Business & Health Editors

PISCATAWAY, N.J.--(BUSINESS WIRE)--May 21, 2002

Enzon

Studies Show Activity in Diverse Patient Populations

Enzon, Inc. (Nasdaq: ENZN) announced today that Schering-Plough Corporation (NYSE: SGP) reported results of several clinical studies presented at the 2002 Digestive Disease Week conference in San Francisco, involving PEG-INTRON(R) (peginterferon alfa-2b) Powder for Injection in combination with REBETOL(R) (ribavirin, USP) Capsules for the treatment of chronic hepatitis C.

In all, 33 studies with PEG-INTRON were presented by clinical investigators.

PEG-INTRON is a longer-acting form of INTRON(R) A (interferon alfa-2b, recombinant) Injection that uses proprietary PEG technology developed by Enzon. Under the Company's licensing agreement with Schering-Plough, Enzon is entitled to royalties on worldwide sales of PEG-INTRON. Schering-Plough holds an exclusive worldwide license to PEG-INTRON.

PEG-INTRON and REBETOL combination therapy received U.S. Food and Drug Administration (FDA) approval in August 2001 for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and are at least 18 years of age.

In an oral presentation, investigators reported clinical data from one of the largest clinical trials studying African Americans with hepatitis C. The study indicated that the commonly lower response rate to treatment among African Americans is not related to genotype, as previously believed. Researchers have attributed lower treatment response rates in African Americans to the fact that this patient population predominantly contracts genotype 1 virus, which is the most difficult to treat. In this study, which compared the treatment response rate of African Americans to response rates of non-Hispanic whites, 98 percent of all patients studied had genotype 1. In the African American patient group, 28% had a virologic response after 12 weeks of therapy compared to a 58% response rate in the non-Hispanic white patient group. At week 24 of treatment, 25% of African Americans tested negative for the virus vs. 62% of non-Hispanic whites, indicating that factors other than genotype were affecting response to therapy.

Researchers enrolled 100 African Americans and 100 non-Hispanic whites who had not been previously treated with alpha interferon therapy into each group. All patients received PEG-INTRON (1.5 mcg/kg/week) for 48 weeks plus REBETOL (1,000 mg/day) for 12 weeks followed by 800 mg/day for 36 weeks. Patients with decompensated liver disease were excluded from the study.

"The low response rate among African Americans has puzzled researchers for years," said Andrew Muir, assistant professor in medicine, division of gastroenterology, Duke University Medical Center. "Even though the response rate in the African American group was lower than in the non-Hispanic white group, treatment with PEG-INTRON and REBETOL combination therapy achieved a higher response than had been seen previously. These results bring us one step closer to understanding how the virus behaves in African Americans and how to effectively treat this patient population." Dr. Muir is the lead investigator for this trial.

Additional PEG-INTRON Studies Presented at DDW 

Preliminary data from the WIN-R trial, the largest ongoing prospective study to evaluate the safety and efficacy of weight-based dosing with PEG-INTRON and REBETOL combination therapy, indicated that patients receiving daily REBETOL dosages (800-1,400 mg) according to their body weight may not have any difference in the rate of significant adverse events than patients receiving a flat daily dose (800 mg) of REBETOL. Both groups were given REBETOL in combination with once-weekly PEG-INTRON (1.5 mcg/kg). Although patients receiving the weight-based dose of REBETOL experienced a moderate increase in anemia, there was no incremental anemia in patients receiving 1,400 mg of REBETOL daily compared to the other doses of REBETOL received in weight-based dosing. Researchers also found no clinically important differences or platelet decreases in neutropenia or loss of white blood cells at the higher ribavirin doses. In addition, patients dosed according to body weight had less severe platelet decreases and similar serious-adverse-event and discontinuation rates than those who had been given the standard 800 mg daily REBETOL dose.

"Data from this large patient population reinforces that PEG-INTRON and REBETOL combination therapy is manageable in hepatitis C patients," said Ira Jacobson, M.D., chief, division of gastroenterology and hepatology, Weill Medical College of Cornell University, New York. "I am encouraged by these results and believe that studies like the WIN-R trial are critical in helping us better define treatment regimens for the many patients with hepatitis C."

The results of the COPILOT (Colchicine versus PEG-INTRON Long-Term) study, which investigated maintenance therapy with PEG-INTRON in patients with advanced cirrhosis, were also presented. In this study, 250 patients with advanced cirrhosis who had previously failed interferon-based therapy were randomized to two groups: 130 patients received once-weekly PEG-INTRON (0.5 mcg/kg) and 120 patients received colchicine (0.6 mg twice-daily). At the end of one year of treatment, the PEG-INTRON group had a reduction in detectable(1) virus (HCV RNA), while the virus levels in the colchicine group remained the same. These findings may be important for patients who have not responded to previous therapy.

PEG-INTRON, which is approved for dosing according to patient body weight, is the first and only pegylated interferon product approved for marketing in the United States. PEG-INTRON, recombinant interferon alfa-2b linked to a 12,000 dalton polyethylene glycol (PEG) molecule, is a once-weekly therapy designed to optimize the balance between antiviral activity and elimination half-life.

Hepatitis C

Some 4 million Americans are infected with the hepatitis C virus (HCV) and approximately 70 percent of infected patients go on to develop chronic liver disease, according to the Centers for Disease Control and Prevention (CDC). Hepatitis C infection contributes to the deaths of an estimated 8,000 to 10,000 Americans each year and this toll is expected to triple by the year 2010, according to the CDC. The CDC has reported that HCV-associated end-stage liver disease is the most frequent indication for liver transplantation among adults. It is predicted that direct U.S. medical costs to treat HCV-related disease will exceed $13 billion for the years 2010

Enzon is a biopharmaceutical company that develops and commercializes enhanced therapeutics for life-threatening diseases through the application of its proprietary platform technologies: PEG Modification and single-chain antibodies (SCA(R)). Three products are currently marketed which utilize Enzon's technology: PEG-INTRON marketed by Schering-Plough for hepatitis C, ONCASPAR(R) for Acute Lymphoblastic Leukemia (ALL), and ADAGEN(R) a treatment for a form of Severe Combined Immunodeficiency Disease (SCID), commonly known as the "Bubble Boy Disease." In addition to three approved products, Enzon has several products in various stages of clinical development by itself and with partners, including additional indications for PEG-INTRON with Schering-Plough. A Phase III clinical trial is being conducted for PEG-INTRON for the treatment of malignant melanoma. Enzon develops and markets products on its own, through strategic alliances and licensing arrangements, which in addition to Schering-Plough Corporation, include Aventis, Alexion Pharmaceuticals, Inc., Baxter Healthcare Corporation, Bristol-Myers Squibb Company, Eli Lilly & Company, Inhale Therapeutics, Inc., and Micromet AG.

Except for the historical information herein, the matters discussed in this news release include forward-looking statements that may involve a number of risks and uncertainties. Actual results may vary significantly based upon a number of factors which are described in the Company's Form 10-K, Form 10-Qs and Form 8-Ks on file with the SEC, including without limitation, risks in obtaining and maintaining regulatory approval for indications and expanded indications, risks that Enzon will not outperform the sector, market acceptance of and continuing demand for Enzon's products and the impact of competitive products and pricing.

This release is also available at http://www.enzon.com

(1) Defined as HCV-RNA below limit of detection using a research-based RT-PCR assay.