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) March 28, 2001
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
ENZON ANNOUNCES EUROPEAN UNION APPROVAL OF PEGINTRON(TM)
AND REBETOL(R)COMBINATION THERAPY FOR HEPATITIS C
Enzon, Inc. announced today that Schering-Plough Corporation was informed
that the European Commission of the European Union (EU) has granted centralized
marketing authorization to 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. PEGINTRON is a longer acting form of
Schering-Plough's INTRON(R) A 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 PEGINTRON.
Commission approval of PEGINTRON and REBETOL results in unified labeling
that is immediately valid in all 15 EU-Member States and Iceland and Norway. The
Commission's decision follows recommendation for approval in December 2000 by
the EU's Committee for Proprietary Medicinal Products (CPMP) of the European
Agency for the Evaluation of Medicinal Products (EMEA).
The pivotal clinical study on which the marketing authorization is based
demonstrated that PEGINTRON and REBETOL combination therapy was significantly
more effective (61% vs. 47%) in achieving a sustained virologic response (SVR)
in patients receiving the recommended combination regimen than the combination
of interferon alfa-2b (INTRON(R) A) and REBETOL, particularly in patients
infected with Genotype 1 virus (48% vs. 33%). SVR is defined as sustained loss
of detectable1 hepatitis C virus (HCV-RNA2) at six months after the cessation of
treatment.
The study showed that SVR rates 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 SVR than those who took <80% of their
treatment (72% vs. 46%).
The authorization recommends PEGINTRON 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-RNA 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
treated in one of 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, SVR rates 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, SVR rates were significantly
higher than in those patients who received <10.6 mg/kg/daily REBETOL.
PEGINTRON 1.5 mcg/kg Once Weekly
Plus >10.6 mg/kg/daily REBETOL
RESULTS: (A) PEG 1.5/R (B) PEG 0.5/R (C) I/R (A) vs. (C)
SVR (overall) 61% 48% 47% (p<0.01)
SVR Genotype 1 48% 34% 33%
SVR Genotypes 2 & 3 88% 80% 79%
In clinical studies, the combination of PEGINTRON and REBETOL had a
comparable safety profile 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 had 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, 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
PEGINTRON granted by Enzon.
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 Enzon's Form 10-K, Form 10-Q's and Form 8-K on
file with the SEC, including without limitation, risks in obtaining and
maintaining regulatory approval for Enzon's products and expanded indications
for such products, 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.
2) HCV-RNA: hepatitis C viral RNA (ribonucleic acid).
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: March 29, 2001
ENZON, INC.
-----------------------------------
(Registrant)
By: /s/ Kenneth J. Zuerblis
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Kenneth J. Zuerblis
Vice President, Finance and Chief Financial Officer