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) December 20, 2000
ENZON, INC.
(Exact name of registrant as specified in its charter)
Delaware 0-12957 22-237286
(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
N/A
(Former name or former address, if changed since last report)
Item 5. Other Events
PEGINTRON(TM) and REBETOL(R) Recommended for Approval as Combination Therapy by
European Union's CPMP for the Treatment of Hepatitis C
Enzon, Inc. (the "Company") announced on December 20, 2000 that the
European Union's (EU) Committee for Proprietary Medicinal Products (CPMP) of the
European Agency for the Evaluation of Medicinal Products (EMEA) has issued a
positive opinion to Schering-Plough Corporation (NYSE:SGP) recommending approval
of PEGINTRON(TM) (peginterferon alfa-2b) Injection and REBETOL(R) (ribavirin)
Capsules as combination therapy for the treatment of both relapsed and naive
(previously untreated) adult patients with histologically proven chronic
hepatitis C.
The CPMP opinion serves as the basis for a European Commission approval,
which is typically issued within three to four months. Commission approval of
the centralized Type II variations to the Marketing Authorizations for PEGINTRON
and REBETOL would result in unified labeling that would be immediately valid in
all 15 EU-Member States.
PEGINTRON has previously received centralized marketing authorization in
the EU and is marketed as monotherapy in cases of intolerance or
contraindication to ribavirin for the treatment of adult patients with
histologically proven chronic hepatitis C. PEGINTRON is a longer-acting form of
Schering-Plough's interferon alfa-2b recombinant injection (marketed as
INTRON(R) A in certain countries), developed using Enzon's proprietary PEG
technology licensed to Schering-Plough. Under the Company's licensing agreement
with Schering-Plough, Enzon is entitled to royalties on worldwide sales of
PEGINTRON and milestone payments.
REBETOL has previously received centralized marketing authorization in the
EU and is marketed for use in combination with Schering-Plough's interferon
alfa-2b injection for the treatment of both relapsed and naive adult patients
with hepatitis C.
The centralized Type II variations propose that PEGINTRON should be
administered as a once-weekly subcutaneous injection at a dose of 1.5 mcg/kg
when used in combination with REBETOL capsules. The dose of REBETOL to be used
in combination with PEGINTRON is based on patient body weight (<65kg/800
mg/daily; 65-85 kg/1,000 mg/daily; >85 kg/1,200 mg/daily). Ribavirin capsules
are to be administered orally each day in two divided doses with food (morning
and evening). It is recommended that patients be treated initially with the
combination therapy for six months. In patients showing loss of HCV-RNA1 at six
months, treatment is to be continued for an additional six months, i.e., one
year of treatment.
Clinical Trials
In a pivotal Phase III, randomized, controlled clinical study of two dosing
regimens of PEGINTRON in combination with REBETOL compared to interferon alfa-2b
(INTRON A) in combination with REBETOL, a total of 1,530 previously untreated
patients from 62 sites worldwide (33 U.S., 5 Canada, 22 Europe, 2 other) were
randomized to three treatment arms:
(A) PEGINTRON Injection 1.5 mcg/kg once weekly (QW) plus REBETOL Capsules 800
mg/daily for 48 weeks (PEG 1.5/R);
(B) PEGINTRON 1.5 mcg/kg QW plus REBETOL 1000-1200 mg/daily for four weeks
followed by PEGINTRON 0.5 mcg/kg QW plus REBETOL 1000-1200 mg/daily for 44
weeks (Peg 0.5/R); or
(C) Interferon alfa-2b (INTRON A) Injection 3 MIU/three times weekly plus
REBETOL Capsules 1000-1200 mg/daily for 48 weeks (I/R). In this study, the
combination of PEGINTRON (1.5 mcg/kg once weekly) and REBETOL was
significantly more effective than the combination of interferon alfa-2b and
REBETOL, particularly in patients infected with Genotype 1 virus. Sustained
virologic response (SVR) was assessed by the response rate six months after
the cessation of treatment.
(D) Sustained virologic response rates in this study were shown to be dependent
on the dose of REBETOL administered in combination with PEGINTRON or
interferon alfa-2b (INTRON A). In those patients who received >10.6
mg/kg/daily REBETOL (800 mg dose in typical 75 kg patient), regardless of
genotype or viral load, response rates were significantly higher than in
those patients who received <10.6 mg/kg/daily REBETOL.
Optimized Weight-Based Dosing
-----------------------------
(>10.6 mg/kg/daily REBETOL*)
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RESULTS: (A) PEG 1.5/R (B) PEG 0.5/R (C) I/R
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SVR (overall) 61% 48% 47%
SVR Genotype 1 48% 34% 34%
SVR Genotypes 2 & 3 88% 80% 80%
* 10.6 mg/kg/daily REBETOL About Equals REBETOL 800 mg/daily for patient
weighing 75 kg.
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Sustained virologic response rates in this study were increased if patients
were able to maintain compliance. Regardless of genotype, patients who received
the recommended combination regimen and received >|=80% of their treatment with
PEGINTRON and REBETOL had a higher sustained response six months after one year
of treatment than those who received <80% of their treatment (72% vs. 46%).
In clinical studies, the combination of PEGINTRON and REBETOL had
comparable safety profiles as the combination of interferon alfa-2b and REBETOL.
The most frequently reported adverse events with PEGINTRON and REBETOL
combination therapy (fatigue, fever, headache and rigors) were also the most
frequently reported adverse events with interferon alfa-2b and REBETOL
combination therapy.
PEGINTRON (peginterferon alfa-2b), interferon alfa-2b linked to a 12,000
dalton polyethylene glycol (PEG) molecule, is a once-weekly product designed to
optimize the balance between antiviral activity and elimination half-life.
Schering-Plough holds an exclusive worldwide license to PEGINTRON.
Chronic hepatitis C is estimated to affect some 10 million people in major world
markets. As many as 5 million Europeans (1 to 2 percent of the general
population) are chronically infected with the hepatitis C virus, according to a
study conducted by the World Health Organization (WHO). In Europe, chronic
hepatitis C is the leading cause of chronic liver disease and the most common
reason for liver transplant.
Except for the historical information herein, the matters discussed herein
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-K
on file with the SEC, including without limitation, risks in obtaining and
maintaining regulatory approval for expanded indications, market acceptance of
and continuing demand for Enzon's products and the impact of competitive
products and pricing.
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: December 20, 2000
ENZON, INC.
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(Registrant)
By: /s/ Kenneth J. Zuerblis
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Kenneth J. Zuerblis
Vice President, Finance and Chief Financial
Officer