FW: NATAP: New Peg-Intron Maintenance Study
- New Peg-Intron Maintenance Study
Press announcement today from Schering Plough. There is a symposium at the
Coinfection Workshop, where I am now, tomorrow morning discussing this
bSCHERING-PLOUGH INITIATES PEG-INTRON MAINTENANCE STUDY
IN PATIENTS COINFECTED WITH HEPATITIS C AND HIVb
ENDURE STUDY TO ASSESS LOW-DOSE PEG-INTRON MONOTHERAPY
IN HELPING TO PREVENT HEPATITIS C DISEASE PROGRESSION IN COINFECTED PATIENTS
AMSTERDAM, Netherlands, Jan. 13, 2006 - Schering-Plough announced today that
it is initiating a large multinational clinical trial to evaluate the use of
low-dose PEG-INTRON (peginterferon alfa-2b) maintenance monotherapy in
preventing or delaying hepatitis C disease progression and thus potentially
reducing the occurrence of clinical events such as liver transplantation,
liver cancer and death in cirrhotic patients with hepatitis C who are
coinfected with HIV. Known as the ENDURE study, the trial is targeted to
enroll 448 patients at approximately 80 sites worldwide, including centers
in the United States, Europe and Canada.
Approximately one third of HIV patients, or about 10 million people
worldwide, are coinfected with the hepatitis C virus (HCV) and HIV.1 Liver
disease caused by chronic hepatitis C is now a leading cause of morbidity
and mortality among HIV-infected patients in the developed world.2,3
Furthermore, studies have shown that HCV can aggravate the course of HIV
bThe principal goal for treating patients infected with hepatitis C is
viral eradication, with pegylated interferon and ribavirin combination
therapy being the current standard of care. However, many coinfected
patients fail to respond to this combination therapy and there currently is
no approved treatment for such patients. Until more effective HCV agents
such as protease and polymerase inhibitors are available, it is critically
important to try to prevent or delay progression of liver disease in these
patients,b said Mark S. Sulkowski, M.D., associate professor of medicine in
the Division of Infectious Diseases, Johns Hopkins University School of
Medicine, Baltimore, USA, and co-lead investigator of the study.
bAnother patient group that may benefit from low-dose PEG-INTRON
maintenance monotherapy is cirrhotic patients with coinfection who are
ineligible for combination therapy due to contraindications to ribavirin or
who simply cannot tolerate full-dose combination therapy,b added co-lead
investigator Massimo Puoti, M.D., associate professor in the Department of
Infectious Diseases, University of Brescia, Italy, directed by professor G.
Carosi. bThe purpose of the ENDURE study is to address this question with
a large, randomized, controlled clinical study.b
ENDURE is a randomized, open-label, multicenter, Phase III, parallel-group
clinical study evaluating the efficacy and safety of maintenance therapy
with low-dose PEG-INTRON (0.5 mcg/kg once weekly) versus standard supportive
care in patients with cirrhotic hepatitis C who are coinfected with HIV.
The primary objective of the study is to compare efficacy for the two
treatment groups at the end of the study, using the time to any of the
following clinical events as primary endpoints: death, liver decompensation,
liver transplant or liver cancer (hepatocellular carcinoma). All patients
will be enrolled within the first 12 months of this 36-month study and
treated until the end of the study or until a clinical event occurs.
Written informed consent will be obtained and all other regulatory
requirements adhered to for all patients participating in the study.
The ENDURE study is consistent with Schering-Plough's research strategy to
conduct and support clinical studies with weight-based PEG-INTRON therapy,
particularly in hepatitis patients with difficult-to-treat forms of the
bAlthough we have made great advances over the past decade in the effective
treatment of chronic hepatitis C, one of the most common blood-borne
infections in the world, improved treatment options are still neededb said
Robert J. Spiegel, M.D., chief medical officer and senior vice president of
medical affairs, Schering-Plough Research Institute. bSchering-Plough is
undertaking studies with our existing hepatitis C products to explore new
approaches to treatment, including maintenance therapy with our ongoing
EPIC3 study5 in HCV patients and the new ENDURE study in coinfected
patients, while at the same time developing new antiviral agents such as our
investigational hepatitis C protease inhibitor.6 These research efforts
underscore our long-term commitment to this therapeutic area and the
PEG-INTRON is approved in the United States as monotherapy and for use in
combination therapy with REBETOLB. (ribavirin, USP) for the treatment of
chronic hepatitis C in patients with compensated liver disease who are at
least 18 years of age, and is not approved for treatment of patients who are
coinfected with HCV and HIV.
PEG-INTRON, recombinant interferon alfa-2b linked to a 12,000 dalton
polyethylene glycol (PEG) molecule, is a once-weekly therapy dosed according
to patient body weight that is designed to achieve an effective balance
between antiviral activity and elimination half-life.
Important Safety Information Regarding U.S. Labeling for PEG-INTRON and
Alpha interferons, including PEG-INTRON, 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 PEG-INTRON
Ribavirin causes hemolytic anemia. Anemia associated with REBETOL therapy
may exacerbate 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. It is advised that complete
blood counts (CBC) be obtained at baseline and at weeks 2 and 4 of therapy
or more frequently if clinically indicated.
REBETOL and combination REBETOL/PEG-INTRON therapy must not be used by
women, or male partners of women, who are or may become pregnant during
therapy and during the 6 months after stopping therapy. REBETOL and
combination REBETOL/PEG-INTRON therapy should not be initiated until a
report of a negative pregnancy test has been obtained immediately prior to
initiation of therapy. Women of childbearing potential and men must use
effective contraception (at least two reliable forms) during treatment and
during the 6-month post-treatment follow-up period. Significant teratogenic
and/or embryocidal effects have been demonstrated for ribavirin in all
animal species in which adequate studies have been conducted. These effects
occurred at doses as low as one twentieth of the recommended human dose of
REBETOL. If pregnancy occurs in a patient or partner of a patient during
treatment or during the 6 months after treatment stops, physicians are
encouraged to report such cases by calling (800) 727-7064.
There are no new adverse events specific to PEG-INTRON as compared to INTRON
A (interferon alfa-2b, recombinant) for Injection, 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 bflu-likeb
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/REBETOL is contraindicated in patients with autoimmune hepatitis,
decompensated liver disease, and in patients with hemoglobinopathies (e.g.,
thalassemia major, sickle-cell anemia).
The following serious or clinically significant adverse events have been
reported at a frequency less than or equal to 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
In the PEG-INTRON/REBETOL combination trial the incidence of serious adverse
events was 17% in the PEG-INTRON/REBETOL groups compared to 14% in the
INTRON A/REBETOL group. The incidence of severe adverse events in the
PEG-INTRON/REBETOL combination therapy trial was 23% in the INTRON A/REBETOL
group and 31-34% in the PEG-INTRON/REBETOL groups. Dose reductions due to
adverse reactions occurred in 42% of patients receiving PEG-INTRON (1.5
mcg/kg)/ REBETOL and in 34% of those receiving INTRON A/REBETOL.
REBETOL should not be used in patients with creatinine clearance less than
Schering-Plough Corporation 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. The company is based in Kenilworth, N.J., USA, and
its Web site is www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release
includes certain bforward-looking statementsb within the meaning of the
Securities Litigation Reform Act of 1995, including statements relating to
PEG-INTRON and the potential market for drugs that treat hepatitis.
Forward-looking statements relate to expectations or forecasts of future
events. Schering-Plough does not assume the obligation to update any
forward-looking statement. Many factors could cause actual results to
differ materially from Schering-Plough's forward-looking statements,
including market forces, economic factors, product availability, current and
future branded, generic or over-the-counter competition and the regulatory
process, among other uncertainties. For further details about these and
other factors that may impact the forward-looking statements, see
Schering-Plough's Securities and Exchange Commission filings, including the
company's third quarter 2005 10-Q.
1. Rockstroh J, Mocroft A, Soriano V, et al. Influence of hepatitis C
coinfection on HIV disease progression within the EuroSIDA cohort for the
EuroSIDA study group. 9th European AIDS Conference (EACS), Warsaw, 2003;
2. Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA,
et al. Declining morbidity and mortality among patients with advanced human
immunodeo,ciency virus infection. HIV Outpatient Study Investigators. N
Engl J Med 1998; 338:853-860.
3. Sulkowski M, Thomas D. Hepatitis C in the HIV-infected person. Ann Intern
Med 2003; 138:197-207.
4. Fischer HP, Willsch E, Bierhoff E, Pfeifer U. Histopathologic findings in
chronic hepatitis C. J Hepatol. 1996;
24 (2 suppl) 35-42.
5. EPIC3 (Evaluation of PEG-INTRON in Control of Hepatitis C Cirrhosis), a
large multicenter, multi-part treatment and maintenance therapy clinical
study involving nearly 4,000 patients at approximately 140 sites worldwide.
Schering-Plough Research Institute.
6. SCH-503034, an investigational oral HCV NS3 protease inhibitor,
Schering-Plough Research Institute.
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