NUTLEY, N.J., Feb. 12 /PRNewswire-FirstCall/ -- Roche announced today that results from the largest study conducted to date evaluating chronic hepatitis C treatment among patients co-infected with HIV and HCV were presented at the 11th Annual Conference on Retroviruses and Opportunistic Infections.
The landmark APRICOT (AIDS Pegasys Ribavirin International Co-infection Trial) study showed 40 percent of patients treated with Pegasys(R) (peginterferon alfa-2a), the most prescribed chronic hepatitis C treatment in the US,* and Copegus(R) (ribavirin), achieved a sustained virological response. Sustained virological response refers to a patient's continued undetectable hepatitis C virus levels in the blood 24 weeks after finishing a course of treatment.
Approximately 30 percent of people in the United States infected with HIV are also infected with hepatitis C. HCV is a leading cause of death in patients with HIV.
"People co-infected with HIV and HCV are considered to be among the most difficult to treat for chronic hepatitis C," said Dr. Douglas Dieterich, Professor of Medicine, Mount Sinai School of Medicine, New York City and co-lead investigator of the APRICOT study. "The strong response rates that we have seen with Pegasys and Copegus therapy in this study are encouraging news for the 300,000 Americans estimated to be infected with HCV and HIV." The randomized, partially blinded international trial enrolled a total of 868 HCV/HIV co-infected patients in 19 countries. All patients were HCV positive, had compensated liver disease, a CD4+ count greater than 100 cells/mL, and stable HIV disease, with or without antiretroviral therapy. Patients were randomized to 48 weeks of treatment with interferon alfa 2a 3MIU three times a week plus 800 mg/day of ribavirin, 180 mcg of Pegasys once weekly plus placebo, or 180 mcg of Pegasys once weekly with 800 mg/day of Copegus. Sustained virological response (SVR) was accessed at the end of 24 weeks of treatment-free follow up (week 72).
Among the key APRICOT findings:
* 62 percent of patients with hepatitis C genotypes 2 and 3 treated with
Pegasys/Copegus achieved a sustained virological response
* 29 percent of patients with genotype 1, the hardest strain of the virus
to treat, treated with Pegasys/Copegus achieved a sustained virological
response
* 20 percent of all patients treated with Pegasys monotherapy achieved a
sustained virological response
* 12 percent of all patients treated with conventional interferon and
ribavirin achieved a sustained virological response
* Serious adverse events were experienced in 5 percent of patients treated
with standard interferon and ribavirin, in 10 percent treated with
Pegasys monotherapy and in 8 percent treated with Pegasys and Copegus
"In the APRICOT study a dramatic improvement in response rates was seen among patients treated with Pegasys combination therapy compared to those treated with Pegasys monotherapy or conventional interferon combination therapy. In addition, the side effects seen in HIV patients treated with Pegasys combination therapy were similar to those we have seen in studies among other hepatitis C patients," said Dr. Francesca Torriani of the University of California, San Diego, and co-lead investigator of APRICOT.
About HCV/HIV Co-infection
Currently, no HCV therapies have been approved for the treatment of chronic hepatitis C in HCV/HIV co-infected patients. Roche will file for an sNDA later this year for this indication. Pegasys in combination with Copegus was approved by the FDA in December 2002, and is the market leader in HCV treatment.
HCV and HIV are the two most prevalent blood-borne infections in the United States, and HCV/HIV co-infection is increasingly recognized as a growing public health problem. In total, approximately 300,000 individuals are estimated to be co-infected in the United States. Chronic HCV affects approximately 2.7 million and HIV affects almost one million Americans.
About Pegasys
Pegasys, a pegylated alpha interferon, and Copegus were approved by the FDA in December 2002 for use in combination for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis.
Pegasys is dosed at 180mcg as a subcutaneous injection taken once a week. Copegus is available as a 200mg tablet, and is administered orally two times a day as a split dose.
Roche has backed Pegasys with the most extensive clinical research program ever undertaken in hepatitis C, with major studies initiated to advance treatment for hepatitis C patients with unmet needs, including patients co- infected with HIV and HCV, African
Americans, patients with cirrhosis, patients with normal ALT levels, and patients who have failed to respond to previous therapy. Please see attached additional important information about Pegasys indication and safety.
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. prescription drug unit of the Roche Group, a leading research-based health care enterprise that ranks among the world's leaders in pharmaceuticals and diagnostics. Roche discovers, develops, manufactures and markets numerous important prescription drugs that enhance people's health, well-being and quality of life. Among the company's areas of therapeutic interest are: dermatology; genitourinary disease; infectious diseases, including influenza; inflammation, including arthritis and osteoporosis; metabolic diseases, including obesity and diabetes; neurology; oncology; transplantation; vascular diseases; and virology, including HIV/AIDS and hepatitis C.
For more information on the Roche pharmaceuticals business in the United States, visit the company's web site at: http://www.rocheusa.com/
* IMS weekly data for the week ending December 26, 2003.
Facts About Pegasys (Peginterferon alfa-2a) in Combination with Copegus
Indication
Pegasys(R), a pegylated alpha interferon, alone or in combination with Copegus(R) (ribavirin, USP) is indicated for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A).
Dosing and Administration
-- Pegasys, a premixed solution, is dosed at 180mcg as a subcutaneous
injection once a week. Copegus, available as a 200mg tablet, is
administered at 800 to 1200mg taken twice daily as a split dose. The
two products are sold separately.
Combination Therapy Clinical Studies
-- The two combination therapy pivotal study findings:
-- Study 5, including 1,284 patients receiving medication, showed that
patients with certain genotypes (strains) of the hepatitis C virus
should be treated with different dosing regimens of Pegasys and
Copegus. The treatment regimens and resulting sustained virological
response rates for these groups treated with Pegasys and Copegus
therapy were:
-- Genotype 1: 48 week duration with 1000 - 1200mg Copegus: 51 percent
-- Genotype non-1: 24 week duration with 800mg Copegus: 82 percent
-- Study 4, published in the September 26, 2002 New England Journal of
Medicine, including 1,121 patients receiving medication, showed that
Pegasys and Copegus combination therapy is a more effective treatment
for chronic hepatitis C than interferon alfa-2b and ribavirin. The
sustained virological response rate in the Pegasys and Copegus treated
patients was 53 percent compared to 44 percent in the interferon alfa-
2b and ribavirin group. Sustained virological response refers to a
patient's continued undetectable serum hepatitis C RNA levels 24 weeks
after finishing a course of treatment.
The Future - Special Populations, HIV/HCV Co-infection
-- Pegasys and Copegus studies have been conducted to evaluate the therapy
for the treatment of African-Americans, who have a substantially higher
prevalence of hepatitis C infection and typically have lower response
rates to hepatitis C therapy than Caucasian Americans.
-- Data from the study showed a 26 percent SVR in African American
patients compared to a 39 percent SVR for Caucasian patients.
Trials have also been conducted to evaluate Pegasys and Copegus treatment in patients co-infected with hepatitis C and HIV and in patients with hepatitis C who failed to achieve a sustained virological response to standard interferon and ribavirin.
-- Data from this study showed the highest SVR ever achieved among co-
infected patients.
Adverse Events
-- Alpha interferons, including Pegasys, 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. Therapy should be withdrawn in patients
with persistently severe or worsening signs or symptoms of these
conditions. In many, but not all cases, these disorders resolve after
stopping Pegasys therapy (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS
and ADVERSE EVENTS in complete product information).
-- Use with Ribavirin. Ribavirin, including Copegus may cause birth
defects and/or death of the fetus. Extreme care must be taken to avoid
pregnancy in female patients and in female partners of male patients.
Ribavirin causes hemolytic anemia. The anemia associated with
ribavirin therapy may result in worsening of cardiac disease.
Ribavirin is genotoxic, mutagenic, and should be considered a potential
carcinogen (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE
EVENTS in complete product information).
-- Pegasys is contraindicated in patients with hypersensitivity to Pegasys
or any of its components, autoimmune hepatitis, and decompensated
hepatic disease (Child-Pugh class B and C) before or during treatment
with Pegasys. Pegasys is also contraindicated in neonates and infants
because it contains benzyl alcohol. Benzyl alcohol has been reported
to be associated with an increased incidence of neurological and other
complications in neonates and infants, which are sometimes fatal.
Pegasys and Copegus therapy is additionally contraindicated in patients
with a hypersensitivity to Copegus or any of its components, women who
are pregnant, men whose female partners are pregnant, and patients with
hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).
-- COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE
PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF
THERAPY. Women of childbearing potential and men must use two forms of
effective contraception during treatment and during the six months
after treatment has concluded. Routine monthly pregnancy test must be
performed during this time. If pregnancy should occur during treatment
or during six months post-therapy, the patient must be advised of the
significant teratogenic risk of Copegus therapy to the fetus.
Physicians and patients are strongly encouraged to report any
pregnancies that do occur to Roche by calling 1-800-526-6367.
-- The most common adverse events reported for Pegasys and Copegus
combination therapy, observed in clinical trials (n=451), were
fatigue/asthenia (65%), headache (43%), pyrexia (41%), myalgia (40%),
irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%),
neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%),
injection site reaction (23%), arthralgia (22%), depression (20%),
pruritus (19%) and dermatitis (16%).
-- Serious adverse events include neuropsychiatric disorders (suicidal
ideation and suicide attempt), serious and severe bacterial infections,
bone marrow toxicity (cytopenia and rarely, aplastic anemia),
cardiovascular disorders (hypertension, arrhythmias and myocardial
infarction), hypersensitivity (including anaphylaxis), endocrine
disorders (including thyroid disorders and diabetes mellitus),
autoimmune disorders (including psoriasis and lupus), pulmonary
disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial
pneumonitis and sarcoidosis), colitis (ulcerative and
hemorrhagic/ischemiccolitis), pancreatitis, and opthalmologic disorders
(decrease or loss of vision, retinopathy including macular edema and
retinal thrombosis/hemorrhages, optic neuritis and papilledema).
-- The complete package inserts for Pegasys and Copegus are available at
http://www.pegasys.com/, or by calling 1-877-PEGASYS.
Roche