SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported) November 12, 2001
ENZON, INC.
(Exact name of registrant as specified in its charter)
Delaware 0-12957 22-2372868
(State or other jurisdiction (Commission (IRS Employer
of incorporation) File Number) Identification)
20 Kingsbridge Road, Piscataway, New Jersey 08854
(Address of principal executive offices) (Zip Code)
Registrant's telephone number, including area code: (732) 980-4500
NA
(Former name or former address, if changed since last report
Item 5. Other Events
ENZON ANNOUNCES RESULTS OF CLINICAL STUDIES
OF PEG-INTRON(TM) AND REBETOL(R) COMBINATION THERAPY FOR HEPATITIS C
REPORTED BY SCHERING-PLOUGH AT AMERICAN ASSOCIATION FOR THE
STUDY OF LIVER DISEASES MEETING
DATA PRESENTED ON WIDE VARIETY OF PATIENT POPULATIONS
Enzon, Inc. announced today that Schering-Plough Corporation has reported
results of several clinical studies presented at the 52nd Annual Meeting of the
American Association for the Study of Liver Diseases (AASLD) in Dallas, Texas on
PEG-INTRON(TM) (peginterferon alfa-2b) Powder for Injection in combination with
REBETOL(R) (ribavirin, USP) Capsules for the treatment of chronic hepatitis C.
In all, clinical investigators presented 28 studies with PEG-INTRON.
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.
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. The
combination therapy was approved for hepatitis C in the European Union (EU) in
March 2001.
In an oral presentation, investigators reviewed clinical data indicating
that PEG-INTRON and REBETOL combination therapy reduces the rate of fibrosis
progression in patients with chronic hepatitis C. The extent of liver fibrosis
is known to be an important prognostic factor in patients infected with the
hepatitis C virus (HCV). Researchers pooled data from four randomized studies
involving 3,010 previously untreated patients with pre- and post-treatment
biopsies who received one of 10 different regimens utilizing either standard or
pegylated alpha interferon and ribavirin. The histological impact of each
regimen was estimated by the percentage of patients with at least one grade
improvement in liver necrosis and inflammation, the percentage of patients with
at least one stage worsening in fibrosis and by the fibrosis progression rate
per year. While all regimens reviewed in this study reduced fibrosis progression
rates in comparison to rates before treatment, PEG-INTRON and REBETOL
combination
therapy showed the greatest improvement in liver necrosis and inflammation and
the lowest rate of fibrosis worsening among these treatment regimens.
"The development of pegylated interferon is a significant advance in the
treatment of hepatitis C, especially when used in combination with oral
ribavirin," said Ira Jacobson, M.D., chief, division of gastroenterology and
hepatology, Weill Medical College of Cornell University, New York. "It is
imperative for us now to better define optimal treatment regimens using these
therapies and further explore their use in treating specific patient
populations," he said. Jacobson is the lead investigator for the largest
prospective hepatitis C study undertaken to date, which is expected to enroll
more than 4,000 U.S. patients. Schering-Plough is supporting this study.
PEG-INTRON Studies Presented at AASLD
A large randomized study is ongoing to evaluate two different dosing
regimens of PEG-INTRON and REBETOL in nonresponders to interferon monotherapy or
combination therapy with ribavirin, or in patients who relapsed following
combination therapy. Of the 330 patients enrolled in this study to date, 152
have completed 24 weeks of treatment (half way through therapy). Combined
results of the two dosing regimens for the subset of patients who did not
respond to prior combination therapy showed that 26% of these patients (29/112)
had a virologic response after 24 weeks of treatment, including patients with
genotype 1 (22/98), the predominant genotype worldwide and the most difficult to
treat.
In another large ongoing study involving patients who failed to clear the
hepatitis C virus following interferon-based therapy, the first 250 patients
enrolled are being treated with PEG-INTRON (1.5 mcg/kg/week) and REBETOL (800
mg/kg/day) for 48 weeks. The next 250 patients enrolled will receive the same
dose of PEG-INTRON, but in combination with a weight-based dose of REBETOL. Of
the 132 patients to date who have received at least 24 weeks of treatment with
PEG-INTRON (1.5 mcg/kg/week) and REBETOL (800 mg/kg/day), 41% are HCV negative.
Of these patients, 31% with genotype 1a and 49% with genotype 1b, as well as 22%
of previous nonresponders and 25% of African Americans, are HCV negative.
In a study designed to evaluate the effect of adherence to therapy on
treatment outcome for HCV patients receiving PEG-INTRON and REBETOL, researchers
performed an analysis on data from the pivotal clinical study involving 1,530
patients that served as the basis for U.S. and EU regulatory approval of the
combination therapy. Analysis of sustained viral response(1) (SVR) rates
according to patient compliance during therapy showed that patients receiving
>= 80% of their total interferon dose and >= 80% of
their ribavirin dose for >80% of the expected duration of therapy had enhanced
SVR rates compared to patients who were not adherent to therapy.
New treatment strategies are needed to maximize HCV viral clearance in the
growing number of patients with chronic hepatitis C who did not respond to, or
had relapsed following, previous interferon-based therapy. Researchers at AASLD
presented interim data from eight separate ongoing prospective studies
evaluating the safety and efficacy of PEG-INTRON and REBETOL combination therapy
in this treatment setting.
Treatment of chronic hepatitis C in patients co-infected with HIV has
become a major issue in the last few years as the prognosis of HIV disease has
improved dramatically with the development of highly active antiretroviral
therapy (HAART). As a consequence, an increasing number of co-infected patients
are prone to develop cirrhosis and end-stage liver disease. Investigators
reported interim results of an ongoing open-label study evaluating the safety
and efficacy of PEG-INTRON (150 mcg/week) and REBETOL (800 mg/day) in 31
co-infected patients previously untreated with interferon, many of whom are
receiving antiretroviral drugs for HIV. After 12 weeks of treatment, serum
HCV-RNA was undetectable in 22 patients (75%) and liver enzyme levels normalized
in 27 patients (85%), with three patients stopping therapy due to adverse
effects. These interim results indicate that longer follow up is warranted.
In a study comparing the public health burden of chronic hepatitis C and
HIV infection in France, researchers using mortality data and natural history
estimates applied the back-calculation method to make projections about
incidence and mortality from HCV and HIV up to 1997. The HCV model applied
natural history and hepatocellular carcinoma mortality data from French national
statistics. The HIV model used AIDS cases reported to the French National
Institute for Public Health Surveillance and HIV/AIDS deaths reported to the
French Institute of Health and Medical Research. These data indicate that the
public health burden of HCV is on the rise in France, while the burden of HIV
may be on the decline.
Hepatitis C virus recurrence after liver transplantation is common and
poses one of the greatest challenges to transplantation for this indication. In
a small study, PEG-INTRON and REBETOL combination therapy was evaluated in six
patients who developed aggressive recurrent HCV after receiving transplants for
HCV-related cirrhosis. Researchers noted that additional clinical studies are
necessary to define duration of therapy and whether treatment will lead to
improved overall patient and graft survival.
A significant number of patients chronically infected with hepatitis C
have cirrhosis or transition to cirrhosis at the time of diagnosis. In order to
define the impact of severe liver
disease on the pharmacokinetics and pharmacodynamics of PEG-INTRON and REBETOL
combination therapy, pharmacokinetic data for REBETOL (1,367 patients) and
pharmacodynamic data for PEG-INTRON in combination with REBETOL (627 patients)
were collected from the pivotal clinical study involving 1,530 patients that
served as the basis for U.S. and EU regulatory approval of the combination
therapy. Additionally, pharmacokinetic data for PEG-INTRON (894 patients) were
collected from the pivotal clinical study involving 1,219 patients that served
as the basis for U.S. and EU regulatory approval of PEG-INTRON monotherapy. The
population models for PEG-INTRON and REBETOL were developed separately and the
severity of hepatic fibrosis was determined by Knodell HAI score. Results of
this analysis suggest that baseline fibrosis score had no effect on the apparent
clearance of REBETOL. For PEG-INTRON, the baseline fibrosis score had no effect
on week 4 clearance. Furthermore, the baseline fibrosis score had no effect on
other pharmacokinetic parameters, (end of treatment) and the time that the
clearance of PEG-INTRON declines to half of the baseline clearance (T50).
Researchers also presented results of a cost-effectiveness study of
PEG-INTRON and REBETOL combination therapy in the initial treatment of hepatitis
C. For this analysis, summary data from the pivotal clinical study involving
1,530 patients that served as the basis for U.S. and EU regulatory approval of
the combination therapy was applied to a previously published and validated
computer cohort simulation to project lifelong clinical outcomes. Their analysis
suggested that PEG-INTRON and REBETOL combination therapy should be considered
cost effective, providing good economic value for its clinical benefit.
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.
Schering-Plough holds an exclusive worldwide license to PEG-INTRON.
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. This toll is expected to triple by the year 2010 and exceed
the number of annual deaths due to AIDS, 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 through 2019, according to a study published in the American Journal
of Public Health.
Except for the historical information herein, the matters discussed in this
Form 8-K 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/A, 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, market
acceptance of and continuing demand for Enzon's products and the impact of
competitive products and pricing.
(1) Defined as HCV-RNA below limit of detection using a research-based RT-PCR
assay at 24 weeks post-treatment.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf by the
undersigned hereunto duly authorized.
Dated: November 26, 2001
ENZON, INC
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(Registrant)
By: /s/ Kenneth J. Zuerblis
--------------------------------------------
Kenneth J. Zuerblis
Vice President, Finance and Chief Financial
Officer