Internet Conference Report
39th EASL - April 14 - 18, 2004, Berlin Germany

Peginterferon Alfa-2b (PEG-Intron) Plus Ribavirin Can Cure HCV Genotypes 2 and 3

The objective of this multicenter Italian study was to prospectively compare efficacy of PEG-Intron (PEG-IFN) alfa-2b and ribavirin (RBV) when given for 12 or 24 weeks in naive pts with chronic HCV genotype 2 or 3.

A total of 280 pts, treated with PEG-IFN alfa-2b 1.0 mcg/Kg sc QW plus RBV 1-1.2 g D, were randomized at a 3:1 ratio to 12 wks (N=210, Group A) or 48 wks (n=70, Group B) course of treatment. 

Efficacy assessment consisted of serum quantitative HCV-RNA at wks 4, 12, and 24 during therapy, and at wk 24 off therapy.  In group A, HCV-RNA negative pts at wk 4 had to stop therapy at wk 12, whereas viremic pts had to stay on therapy until wk 24. 

Results

In 130 pts in group A who experienced HCV clearance within 4 wks, EVR was 99.2%, SVR 89.2%, whereas 10% of pts relapsed off therapy. 

The remaining 80 pts from group A, viremic at wk 4, experienced EVR of 81.2% after 6 months of tx, SVR of 78.7% at 6 months off tx, whereas 2.5% of them relapsed at follow-up. 

In the 70 pts from group B, EVR and SVR were both 81.4% with no relapse.  No correlation between baseline viremia and relapse was found.

Conclusions

The majority of pts with genotypes 2 or 3 and early viral clearance can be cured by only 12 wks of treatment with PEG-IFN alfa-2b and RBV.  Longer treatment with combination therapy may be needed only in pts still viremic at wk 4. 

04/19/04

Reference
A Mangia and others. HCV GENOTYPE 2 AND 3 CAN BE CURED BY PEG-IFN-ALFA-2B AND RBV FOR 12 WKS: A RANDOMIZED CONTROLLED STUDY. Abstract 93. 39^th EASL. April 14-18, 2004. Berlin, Germany.

www.hivandhepatitis.com

News Release Sunday 18 April 2004, 10:00 GMT

Sunday 18 April 2004 HEALTH MEDICAL Schering-Plough Europe

Schering-Plough Reports New Data Showing Patients with Hepatitis C Genotypes 2 and 3 May Benefit from Shorter Course of Treatment with PegIntron and Rebetol Combination Therapy

    -  Identification of non-responders with genotype 1 using HCV Core  
        Antigen testing (Poster #466)(4); 
    -  PegIntron plus Rebetol combination therapy in the retreatment of non- 
        responders previously treated with interferon alfa-2b or interferon  
        alfa-2b plus ribavirin (Poster #457)(5);  
    -  PegIntron plus Rebetol combination therapy for the treatment of  
        recurrent HCV infection after liver transplant (Poster #489)(6);  
    -  PegIntron monotherapy or in combination with lamivudine in patients  
        with hepatitis B (Posters #446, 447 and 423)(7-9); and  
    -  The use of PegIntron monotherapy in patients with acute hepatitis C  
       (Posters #469, 510 )(10,11).  

    References: 
    (1)  Mangia, A.1, N.Minerva3, GL Ricci10, M.Romano8, V.Carretta4,  
         M.Persico9, D.Bacca6, F.Spirito1, F.Vinelli2, M.Annese5,  
         A.Giangaspero7, G. Scotto2, A.Andriulli1, Gastroenterology - IRCCS  
         "CSS" San Giovanni Rotondo1, Ospedali Riuniti Foggia2, Medicina  
         Ospedali di Canosa3, Venosa4, Policoro5, Casarano6, Bari7, Ospedale  
         "S.Pertini" Roma8, Universita Napoli9, "La Sapienza" Roma10, HCV  
         Genotype 2 and 3 Can Be Cured by Peg-IFN-ALFA-2B and RBV for 12  
         Weeks: A Randomized Controlled Study 
 
    (2)  Sustained Virological response (SVR) is defined as the sustained  
         undetectability of HCV-RNA in the blood six months following the end  
         of treatment.  SVR is the standard criterion for efficacy.   
 
    (3)  Rapid viral response is defined as achieving undetectable HCV-RNA in  
         the blood at week four of treatment. 
 
    (4)  M. Buti et al, HCV Core AG as a Predictor of Non-Response in 
         Genotype 1 Chronic Hepatitis C Patients Treated with PegInterferon
         Alfa-2B Plus Ribavirin 
 
    (5)  C. Bapin et al, Retreatment with Pegylated Interferon Alpha-2B and  
         Ribavirin in Patients with Chronic Hepatitis C Non-Responders to  
         Interferon Monotherapy or Interferon and Ribavirin Combination.  A  
         Prospective Randomized Pilot Study of Two Regimens: Induction versus  
         Regular Dose Pegylated Interferon 
 
    (6)  S. Lorenzini et al, Pegylated Interferon Plus Ribavirin for the  
         Treatment of Recurrent HCV Infection After Liver Transplantation  
 
    (7)  M. van Zonneveld et al, Liver Histology in Chronic Hepatitis B  
         Patients After 1 Year of Treatment with Pegylated Interferon 
         Alpha-2B in Combination with Lamivudine or Placebo 
 
    (8)  M. van Zonneveld et al, Viral Dynamics During Peg-Interferon Alone  
         and in Combination with Lamivudine 
 
    (9)  H.L.Y. Chan et al, A Randomized Trial of PegInterferon Alfa-2B and  
         Lamivudine Combination Treatment versus Lamivudine Monotherapy in  
         Chinese Patients with HBEAG-Positive Chronic Hepatitis B 
 
    (10) G. Calleri et al, Short Course of Pegylated Alfa Interferon in Acute  
         HCV Hepatitis 
 
    (11) T. Santantonio et al, Efficacy of Peg-Interferon Alpha-2B 
         (PegIntron) Monotherapy in Acute Hepatitis C: A Preliminary
         Analysis 
 
     Media:      Robert J. Consalvo    +1 (908) 298-7409 
                                       +447766728282 (onsite at EASL) 
                 Mary-Frances Faraji   +1 (908) 298-7109 
                                       +1 (908) 265-6695(onsite at EASL) 
 
     Investors:  Lisa W. DeBerardine   +1 (908) 298-7437 
                 Janet M. Barth        +1 (908) 298-7417 

Internet Conference Report
39th EASL - April 14 - 18, 2004, Berlin Germany

Black Patients with HCV Genotype 1 in a Study of Veterans Have a Lower Sustained Viral Response Rate Due to Lower Neutrophil Count

Large prospective HCV treatment studies with few black patients (<5%) reported that their SVR rate was lower than in white patients, owing to a higher frequency of HCV genotype 1 (GT-1) in blacks.

Overall, 813 patients (25.4% black, 70.5% white, 4.1% others) were prospectively followed during and after standard therapy with interferon alfa-2b 3 MU TIW + ribavirin 1000-1200 mg/d.

Results

Black patients (GT-1, 85.3%) had a lower SVR rate (7.9%) than white patients (GT-1, 63.2%, SVR=21.5%, p<0.001).  Within GT-1, blacks still had a lower SVR rate (5.8%) than whites (14.1%, p=0.011), but not within GT 2-4 (p=0.56). 

Multi-variable logistic regression analysis using known factors associated with SVR (age, sex, GT, HCV viral load, race, HIV status, and fibrosis) found 3 factors to be independently associated with SVR rate:

• GT-1
• Bblack race; and
• Metavir fibrosis stage 3-4. 

When 4 further factors (all different between blacks and whites), namely ferritin, alpha-fetoprotein, hemoglobin, and neutrophil count (black=2.900/mm3 vs. white=4,100/mm3, p<0.001) were added to the logistic regression model, only 2 factors emerged as independently associated with SVR:

• GT-1; and
• Neutrophil count.

Thus, after adjusting for neutrophils count, black race was no longer associated with SVR rate.

04/26/04

Reference
N Brau and others. BLACK PATIENTS INFECTED WITH HCV GENOTYPE 1 HAVE A LOWER SUSTAINED VIRAL REPONSE (SVR) RATE TO THERAPY WITH INTERFERON + RIBAVIRIN THAN WHITE PATIENTS, AND THIS IS EXPLAINED BY THEIR LOWER NEUTROPHIL COUNT. A PROSPECTIVE MULTICENTER STUDY OF 813 U.S. VETERANS. Abstract 465. 39^th EASL. April 14-18, 2004. Berlin Germany.

www.hivandhepatitis.com

Internet Conference Report
39th EASL - April 14 - 18, 2004, Berlin Germany

HCV Genotypes and Pediatric HCV Infection

Pediatric HCV infection, with its peculiar aspects (perinatal exposure, lack of liver damage cofactors, histologically mild disease) is an interesting model to investigate the clinical significance of HCV genotypes.

373 consecutive HCV RNA+, otherwise healthy, children from 15 Observatory centers were studied (InnoLipa) at the University of Padua, Italy.

The following patterns were recorded: 1a=73 cases (20%, median age at entry=54 mo, maternal infection=56%); 1b=154 cases (41%, age=72 mo, maternal infection=44%); 2=63 cases (17%, age 102 mo, maternal infection=40%); 3=54 cases, (14%, age 17 mo; maternal infection=83%); 4=19 (5%, age 24 mo, maternal infection=100%); other types=3%.

The table below shows the rates of sustained (=>2 years) HCV RNA clearance in treated and untreated children (mean follow-up: 5.0+/-3.1 years). Persistent viremia with normal ALT was recorded in 37% children with genotype 2.

Conclusions

Genotype 3 is significantly associated with spontaneous viremia clearance early in life; children with genotype 2 have often a biochemically mild disease; both types 2 and 3 are predictors of sustained response to IFN.

04/26/04

Reference
F Bortolotti and others. HCV GENOTYPES AND PEDIATRIC HCV INFECTION. Abstract 464. 39^th EASL. April 14-18, 2004. Berlin Germany

www.hivandhepatitis.com

Twice a Week Administration of PEG-Intron Plus Ribavirin in Obtaining SVR Among Patients with HCV Genotype 1

Once a week administration of peginterferon alfa-2b (PEG-Intron) produces an exponential decrease of serum drug's level to almost undetectable at days 6 and 7. The aim of this Italian study was to evaluate whether twice a week administration may improve sustained virological response (SVR) in hepatitis C patients.

Sixty five patients (38 men/27 women, age range 20-65) with chronic hepatits C were subsequently enrolled among outpatients.

Twenty-two (7 genotype 2, 15 genotype 1) received PEG-Intron 1.5 mcg/kg once a week (group A), and 43 (17 genotype 2, 26 genotype 1), received PEG-Intron twice a week (mean dose 2.4 mcg/kg/week) (group B). Both groups received ribavirin 11 mg/kg/day.

Groups were comparable for rate of naive, non responders and relapsers, for prevalence of genotype 1, for male/female ratio and for age of patients.

Genotype 1 patients were treated for 48 weeks, genotype 2 for 24 weeks. The follow-up period was 24 weeks.

Results

End of treatment response was higher in group B for genotype 1 (58% vs 27%, p= 0.055). SVR was higher in group B for genotype 1 (46% vs 27%, p= 0.033).

Overall early response was higher in group B than group A (53% vs 27%, p= 0.044). Among naive patients SVR was higher in group B (72% vs 25%, p=0.024).

Total dropouts were 7 on 15 (32%) and 8 on 35 (19%) for group A and B respectively.

Conclusions

In a non selected population of patients with chronic hepatitis C, twice a week administration of PEG-Intron is more effective than once a week administration in genotype 1 naive patients.

Tolerability and adherence to treatment was higher for the twice a week group (B), probably because the twice a week administration is able to induce tachyphilaxis, producing a continuous drug exposure.

05/17/04

Reference
F Lodato and others. Superior Efficacy of Twice a Week Administration of Peginterferon Alfa-2b plus Ribavirin in Obtaining SVR in HCV Genotype 1. Abstract 122. Digestive Disease Week 2004. May 15-20. New Orleans, LA.

Results of a new study
published in the current issue of the New England Journal of Medicine show
that in patients who have chronic hepatitis C, genotype 1 -- the most common
form of the disease and difficult to treat successfully

Study Reports Results in African American Patients and Non-Hispanic Whites

    KENILWORTH, N.J., May 26 /PRNewswire-FirstCall/ -- Results of a new study
published in the current issue of the New England Journal of Medicine show
that in patients who have chronic hepatitis C, genotype 1 -- the most common
form of the disease and difficult to treat successfully -- non-Hispanic whites
achieved one of the highest response rates reported to date, but response
rates in African Americans were significantly lower.(1)  The findings
challenge much of the current thinking about why African Americans respond
less well to hepatitis C treatment and underscore the need for further
clinical research.
    In the large open-label study, non-Hispanic white patients achieved a
sustained virologic response (SVR) rate of 52 percent, which was significantly
higher than the 19 percent seen in African American patients (p < 0.001).  SVR
is the sustained undetectability of the hepatitis C virus for six months
following therapy.  Lower SVR rates in African Americans, as seen in this
study, also have been seen in past studies using other forms of interferon
therapy, (2,3,4,5) including the newer peginterferon and ribavirin combination
therapies.(6,7)
    "The sustained virologic response rates achieved in this study in genotype
1 patients demonstrate that peginterferon alfa-2b and ribavirin combination
therapy is effective," said lead investigator Andrew Muir, M.D., assistant
professor of medicine, Division of Gastroenterology, Duke University Medical
Center, Durham, North Carolina.  He noted that the study was conducted in a
"real-world" community setting, rather than in a more restrictive clinical
trial.  "However, the lower response rate in African Americans poses a
critical challenge because even with the best therapies currently available,
African American patients clearly have a lower response rate."
    In the study, 100 African American and 100 non-Hispanic white patients
with chronic hepatitis C, genotype 1, were treated with a regimen of
peginterferon alfa-2b (1.5 mcg/kg/weekly) and 1,000 mg of ribavirin daily for
the first 12 weeks and then 800 mg daily thereafter, for a total of 48 weeks.
Growth factors were not used.  The current U.S. label for peginterferon alfa-
2b (1.5 mcg/kg/week) recommends that it be used in combination with 800 mg of
ribavirin daily.  The investigators analyzed a number of variables, including
patients' socio-demographic and clinical characteristics, and found that only
race was significantly associated with the difference in SVR rates.
    The study demonstrated the safety and tolerability of peginterferon alfa-
2b and ribavirin combination therapy in these patients, and showed that the
rates and types of adverse events were similar in the African American and
non-Hispanic white patient groups.  Importantly, the rate of dose reduction of
peginterferon alfa-2b because of neutropenia was similar in the two groups (13
vs. 14 percent, respectively) as was the rate of discontinuation due to
neutropenia (4 vs. 3 percent, respectively).  Neutropenia often is a concern
when treating African Americans, as seen in previous clinical studies.(6,8)

    Challenging Current Thinking
    Dr. Muir said the reasons for the different responses seen in the racial
groups remains unknown, but the study results counter at least some previously
held hypotheses.  For example, some suggested the disparity could be due to a
higher prevalence of hepatitis C, genotype 1, in African Americans, but in
this study 98 percent of both racial groups had that form of the virus.
Further analyses showed that other variables -- including age, sex, education,
body weight, initial viral load, duration of HCV infection and other clinical
factors -- had no significant effect on response.  "Showing these other
factors are not the reason for the difference in response rates adds to our
understanding of the disease and is important in furthering research to
identify what factors actually are responsible.  We can speculate about what
those causes might be, but we need additional clinical studies to get real
answers," he said.

    Importance of Treatment
    "While we are concerned about these findings in African Americans, it is
critical to point out that many of these patients do, in fact, respond to
hepatitis C treatment, so it is vitally important for an infected individual
to aggressively pursue, with their physician, evaluation for therapy," urged
Jonathan McCone, M.D., director, Mount Vernon Endoscopy Center in Alexandria,
Va., and a participating investigator in the study.  He noted that hepatitis
C, the most common blood-borne infection in America, affects approximately 4
million people, including a disproportionately high percentage of African
Americans.  Chronic hepatitis C infection substantially increases the risk of
cirrhosis and liver cancer, and is the most frequent indication for liver
transplantation among adults.  "Timely therapy can help achieve a sustained
virologic response," McCone said, "and patients can improve their chances of
achieving an SVR by adhering to therapy."
    Dr. Muir concurred, noting that the study found a higher SVR rate (23
percent) among African Americans who completed the full course of therapy.

    A Patient's Perspective
    The importance of adhering to treatment is exemplified by Jackie Boykin,
R.N., 41, an African American woman who contracted hepatitis C in the course
of her work as a nurse.  While not a participant in the study by Muir and his
colleagues, she was treated at Duke University Medical Center.  In 2002,
Boykin received combination therapy with PEG-INTRON(R) (peginterferon alfa-2b)
Powder for Injection and REBETOL(R) (ribavirin, USP) Capsules.  She achieved
an SVR and has been virus free for nearly one-and-a-half years.  As a result
of her experience, Boykin counsels many patients with hepatitis C to stay with
the therapy "because compliance is so important to treating the disease," she
said.
    "I found the Schering-Plough PEG-INTRON Web site very helpful, and the
support I received from the nurses in the Be In Charge program helped me stay
on therapy."  Schering-Plough's Be In Charge hepatitis C patient-support
program provides educational materials and telephone contact with registered
nurse counselors skilled in the management of hepatitis C.  "Support from
family, the community and medical professionals is critical for hepatitis C
patients," Boykin said.  She continues to attend a hepatitis C patient support
group at Duke University Medical Center.

    Commitment to Hepatitis C Research
    Schering-Plough, which supported the study by Muir and colleagues, is
committed to improving outcomes of hepatitis C treatment in African Americans.
The company's ongoing efforts include the WIN-R trial (Weight Based Dosing of
PEG-INTRON and REBETOL), an investigator-initiated study supported by
Schering-Plough that is the largest prospective clinical study in hepatitis C
undertaken to date, involving approximately 4,900 patients from 250 centers
throughout the United States.  It includes the largest number of African
American patients in any hepatitis C study to date.  Results in African
American study participants are expected to be reported in the near future.
    To further illustrate the efficacy of individualized, weight-based PEG-
INTRON therapy, Schering-Plough Research Institute is conducting comparative
studies with the two approved forms of pegylated interferon.  Foremost among
these is the IDEAL Study (Individualized Dosing Efficacy vs. flat dosing to
Assess optimaL pegylated interferon therapy), a major randomized clinical
study involving 2,880 patients that is directly comparing the efficacy and
safety of individualized weight-based dosing with PEG-INTRON and REBETOL
versus PEGASYS (peginterferon alfa-2a), which is administered as a flat dose
to all patients regardless of individual body weight, and COPEGUS (ribavirin,
USP) dosed either at 1,000 mg or 1,200 mg, in U.S. patients with chronic
hepatitis C, genotype 1.  PEGASYS and COPEGUS are trademarks of Hoffmann-La
Roche Inc.

    Commitment to Hepatitis C Patients
    In addition to its ongoing commitment to research and development,
Schering-Plough is committed to supporting hepatitis C patients with education
and service programs as well as to help locate reimbursement assistance for
patients in need.  The company's programs for patients in the United States
are among the most comprehensive in the industry, providing support and
guidance to patients, and ensuring that all eligible patients have access to
the company's hepatitis C products.
    Schering-Plough's Be In Charge hepatitis patient-support program has
helped more than 100,000 people in the United States since its inception in
1997.  This U.S. program is designed to support patients diagnosed with
hepatitis C as well as patients treated with Schering-Plough's interferon-
based therapies through the use of educational materials and telephone contact
with registered nurse counselors who are available 24/7 and skilled in the
management of hepatitis C.
    The company's Commitment to Care program is designed to ensure that
eligible U.S. patients have access to Schering-Plough's hepatitis products,
either by assisting patients in obtaining the reimbursement or assistance for
which they qualify, or by providing products free of charge to eligible
patients.  The market value of treatment provided to hepatitis C patients
through this program in 2003 exceeded $150 million.

    PEG-INTRON Combination Therapy
    PEG-INTRON is the only peginterferon approved for dosing according to
patient body weight.  It is a longer-acting form of INTRON(R) A (interferon
alfa-2b, recombinant) Injection that uses proprietary PEG technology developed
by Enzon, Inc. (Nasdaq: ENZN) of Bridgewater, N.J.  PEG-INTRON, recombinant
interferon alfa-2b linked to a 12,000 dalton polyethylene glycol (PEG)
molecule, is a once-weekly therapy that is designed to achieve an effective
balance between antiviral activity and elimination half-life.  Schering-Plough
holds an exclusive worldwide license to PEG-INTRON.

    WARNING
    -- REBETOL monotherapy is not effective for the treatment of chronic
hepatitis C virus infection and should not be used alone for this indication.
(See WARNINGS.)
    -- The primary toxicity of ribavirin is hemolytic anemia.  The anemia
associated with REBETOL therapy may result in worsening of cardiac disease
that has led to fatal and nonfatal myocardial infarctions.  Patients with a
history of significant or unstable cardiac disease should not be treated with
REBETOL.  (See WARNINGS, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION.)
    -- Significant teratogenic and/or embryocidal effects have been
demonstrated in all animal species exposed to ribavirin.  In addition,
ribavirin has a multiple-dose half-life of 12 days, and so it may persist in
nonplasma compartments for as long as 6 months.  Therefore, REBETOL therapy is
contraindicated in women who are pregnant and in the male partners of women
who are pregnant.  Extreme care must be taken to avoid pregnancy during
therapy and for 6 months after completion of treatment in both female patients
and in female partners of male patients who are taking REBETOL therapy.  At
least two reliable forms of effective contraception must be utilized during
treatment and during the 6-month post-treatment follow-up period.  (See
CONTRAINDICATIONS, WARNINGS, PRECAUTIONS -- Information for Patients and
Pregnancy Category X.)
    -- Alpha interferons, including PEG-INTRON and INTRON A, may cause or
aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic and
infectious disorders.  Patients should be monitored closely with periodic
clinical and laboratory evaluations.  Patients with persistently severe or
worsening signs or symptoms of these conditions should be withdrawn from
therapy.  In many but not all cases these disorders resolve after stopping
therapy with PEG-INTRON or INTRON A.  (See WARNINGS, ADVERSE REACTIONS.)

    PEG-INTRON
    There are no new adverse events specific to PEG-INTRON as compared to
INTRON A, however, the incidence of some (e.g., injection site reactions,
fever, rigors, nausea) were higher.  The most common adverse events associated
with PEG-INTRON were "flu-like" symptoms, occurring in approximately 50% of
patients, which may decrease in severity as treatment continues.  Application
site disorders were common (47%), but all were mild (44%) or moderate (4%) and
no patient discontinued, and included injection site inflammation and reaction
(i.e., bruise, itchiness, irritation).  Injection site pain was reported in 2%
of patients receiving PEG-INTRON.  Alopecia (thinning of the hair) is also
often associated with alpha interferons including
PEG-INTRON.
    Psychiatric adverse events, which include insomnia, were common (57%) with
PEG-INTRON, but similar to INTRON A (58%).  Depression was most common at 29%.
Suicidal behavior including ideation, suicidal attempts, and completed
suicides occurred in 1% of patients during or shortly after completing
treatment with PEG-INTRON.  PEG-INTRON is contraindicated in patients with
autoimmune hepatitis and decompensated liver disease.
    The following serious or clinically significant adverse events have been
reported at a frequency <1% with PEG-INTRON or interferon alpha:  Severe
decreases in neutrophil or platelet counts, hypothyroidism, hyperglycemia,
hypotension, arrhythmia, ulcerative and hemorrhagic colitis, development or
exacerbation of autoimmune disorders including thyroiditis, RA, systemic lupus
erythematosus, psoriasis, pulmonary disorders (dyspnea, pulmonary infiltrates,
pneumonitis and pneumonia, some resulting in patient deaths), urticaria,
angioedema, bronchoconstriction, anaphylaxis, retinal hemorrhages and cotton
wool spots.
    Renal failure patients should be closely monitored for signs and symptoms
of interferon toxicity and PEG-INTRON should be used with caution in patients
with creatinine clearance <50 mL/min.  Patients on PEG-INTRON therapy should
have hematology and blood chemistry testing before the start of treatment and
then periodically thereafter.

    INTRON A
    All patients receiving INTRON A therapy experienced mild-to-moderate side
effects.  Some patients experienced more severe side effects, including
neutropenia, fatigue, myalgia, headache, fever, chills and increased SGOT.
Other frequently occurring side effects were nausea, vomiting, depression,
alopecia, diarrhea and thrombocytopenia.  DEPRESSION AND SUICIDAL BEHAVIOR,
INCLUDING SUICIDAL IDEATION, SUICIDAL ATTEMPTS, AND COMPLETED SUICIDES, HAVE
BEEN REPORTED IN ASSOCIATION WITH TREATMENT WITH ALFA INTERFERONS, INCLUDING
INTRON A THERAPY.

    DISCLOSURE NOTICE:  The information in this press release includes certain
"forward-looking" statements concerning PEG-INTRON, the market for drugs to
treat hepatitis and Schering-Plough's products.  Forward-looking statements
are subject to risks and uncertainties, which may cause actual results to
differ materially.  These risks and uncertainties include product
availability, current and future branded, generic and OTC competition, the
regulatory process for new products and new indications, market acceptance of
new products and new indications, timing of trade buying, and patent
positions.  For further details and a discussion of these and other risks and
uncertainties, see the company's past and future Securities and Exchange
Commission filings, including the company's first quarter 2004 10-Q.
    Schering-Plough is a global science-based health care company with leading
prescription, consumer and animal health products.  Through internal research
and collaborations with partners, Schering-Plough discovers, develops,
manufactures and markets advanced drug therapies to meet important medical
needs.  Schering-Plough's vision is to earn the trust of the physicians,
patients and customers served by its more than 30,000 people around the world.
    For more information about Schering-Plough, visit the company's Web site
at http://www.schering-plough.com.
    For information about hepatitis and for full prescribing information
regarding PEG-INTRON and REBETOL, visit http://www.hepatitisinnovations.com.
    For more information about the IDEAL Study, visit the study's Web site at
http://www.idealstudy.com.
    PEGASYS and COPEGUS are trademarks of Hoffmann-La Roche Inc.  See the
PEGASYS and COPEGUS product inserts for information on these products.

    References:

    (1) Muir AJ, Bornstein JD, Killenberg PG, for the Atlantic Coast Hepatitis
Treatment Group. Peginterferon alfa-2b and ribavirin for the treatment of
chronic hepatitis C in African Americans and Non-Hispanic Whites.  N Engl J
Med 2004; 350(22):27-33.
    (2) Reddy KR, Hoofnagle JH, Tong MJ, Lee WM, Pockros P, Heathcote EJ,
Albert D, Joh T. Racial differences in responses to therapy with interferon in
chronic hepatitis C.  Hepatology 1999; 30:787-93.
    (3) Kinzie JL, Naylor PH, Nathani MG, Peleman RR, Ehrinpreis MN, Lybik M,
Turner JR, Janisse JJ, Massanari M, Mutchnick MG. African Americans with
genotype 1 treated with interferon for chronic hepatitis C have a lower end of
treatment response than Caucasians.  J Viral Hepat 2001;8:264-9.
    (4) De Maria N. Colantoni A. Idilman R. Friedlander L. Harig J. Van Thiel
DH. Impaired response to high-dose interferon treatment in African-Americans
with chronic hepatitis C.  Hepatogastroenterology 2002;49:788-92.
    (5) McHutchison JG, Poynard T, Pianko S, Gordon SC, Reid AE, Dienstag J,
Morgan T, Yao R, Albrecht J. The impact of interferon plus ribavirin on
response to therapy in black patients with chronic hepatitis C.
Gastroenterology 2000;119:1317-23.
    (6) Howell CD, Jeffers LS, Hu S, Lopez-Talavera JC.  Safety and adherence
to peginterferon alfa-2a (40KD) plus ribavirin (RBV) in black Americans with
chronic hepatitis C (CHC) HCV genotype 1.  Poster presentation M1236 (Abstract
No. 106885) at Digestive Disease Week, New Orleans, LA, May 15-20, 2004.
    (7) Jeffers LJ, Cassidy W, Howell C, Reddy R, Sheridan S, Ho I, Khouri S,
Harb G.  Peginterferon alfa-2a (40kd) (Pegasys) in combination with ribavirin
in African American and Caucasian patients with chronic hepatitis C virus
genotype 1: results of a multicenter study.  Abstract 71, oral presentation
at: 54th annual meeting of the American Association for the Study of Liver
Diseases, Boston, MA, October 24-28, 2003.
    (8) Howell C, Jeffers LJ, Cassidy W, Reddy R, Sheridan S, Ho I, Khouri S,
Harb G.  Peginterferon alfa-2a (40kd) (Pegasys) in combination with ribavirin
in African American and Caucasian patients with chronic hepatitis C HCV
genotype 1: safety and tolerability. Abstract 332, poster presentation at:
54th annual meeting of the American Association for the Study of Liver
Diseases, Boston, MA, October 24-28, 2003.

Histopathological Effects of Pegylated and Standard Interferon in Responders and Non Responders Chronic Hepatitis C Genotype 4

Gamal Esmat, Khalid Zalata, Mohamed Metwally, Mohamed Abdel Hamid, Amr Abouzied, Maissa El Raziky, Mohamed El Batanony, Thomas Strickland, Maria Sjogren

Background

Egypt has a high prevalence of hepatitis C (HCV) (more than 10%) with predominant genotype 4 (more than 90%). Data about response to and histological benefit of interferon therapy in genotype 4 are limited. Aim: Study the histological effect of treatment with pegylated and standard interferon in chronic HCV genotype 4.

Methods

In a randomized controlled trial to study the effect of pegylated interferon alfa 2b/ribavirin against standard interferon/ribavirin, 100 patients were recruited to each arm. All patients had pretreatment liver biopsy and 97 (49 in pegylated group and 48 in standard group) had liver biopsy at week 72 of therapy. Demographic, laboratory and hisopathological data of liver biopsy (based on modified Ishac score) were collected. Regression of fibrosis or inflammation was defined as at least one stage decrease from the pretreatment stage or score.

Results

Out of 97 patients, 56 (57.7%) had sustained virological response (SVR)(63.3% of pegylated group and 52.1% of standard group). Regression of fibrosis (decrease of fibrosis by at least one stage) was found in 39/97 (40.2%). Regression in fibrosis was not related to lower pre-treatment viral load, type of therapy or SVR (P=0.5, 0.3 and 0.2 respectively).  Regression of inflammatory activity was found in 74/97 (76.3%). Regression of inflammatory activity was significantly associated with SVR (P=0.0001).  In summary, in logistic regression analysis, the only independent predictor for regression of inflammatory activity is the presence of SVR (p=0.001)

Conclusions

1) A substantial number of patients had regression of fibrosis and inflammation either treated with standard or pegylated IFN.

2) Patients with SVR had more regression in inflammation than patients with no SVR; however both groups had equal regression of fibrosis.

3) Long term benefit from the regression in responders and non responders should be studied.