PEGASYS® (Peginterferon alfa-2a) Efficacy – HIV and Hepatitis C Coinfection

PEGASYS® (Peginterferon alfa-2a) for Injection

Long term and short term success begins here

Because we know that the best treatment plan goes beyond medication.

Patients with HCV/HIV coinfection: a unique population with rapid progression of liver disease

HIV treatment typically requires a combination of 3 or 4 antiretroviral drugs—a regimen known as highly active antiretroviral therapy (HAART).

In the era of HAART, the mortality rate associated with HIV infection has declined, and ESLD has become the primary cause of death in patients with HCV/HIV coinfection.^1,2

Pre-HAART (1991) liver disease mortality rate: 12%
HAART era (1998-1999) liver disease mortality rate: 50%

In a retrospective study, among patients dying from ESLD in the HAART era²

55% had undetectable plasma HIV RNA levels and/or CD4 cell counts
>200 cells/mm³
Most of the patients that were tested had detectable antibodies to HCV

Due to the effectiveness of HIV treatment with HAART, more HCV/HIV coinfected patients are dying from ESLD.^1,2

Most common causes of death in HCV/HIV coinfected patients

Adapted from Salmon-Ceron D et al. J Hepatol. 2005;42(6):799-805.

HCV/HIV coinfected patients progress more rapidly to cirrhosis or decompensated liver disease than HCV monoinfected patients³

A prospective evaluation of change in fibrosis stage between paired liver biopsies of HCV/HIV coinfected patients suggests more rapid progression of fibrosis in coinfected patients⁴

Fibrosis Stage on Second Biopsy

In this study, more than 25% of HCV/HIV coinfected patients (N=67) progressed from mild to significant fibrosis in less than 3 years⁴

Median time between biopsies was 2.84 years
37% of patients progressed 2 or more stages

Mean time to cirrhosis (years)

Adapted from Soto B. J Hepatol. 1997;26(1):1-5

In fact, progression to cirrhosis occurs 3 times faster in HCV/HIV coinfected patients compared with those who are HCV monoinfected⁵

Additionally, HCV/HIV coinfected patients have a 6 times greater relative risk of decompensated liver disease than HCV monoinfected patients³

Determining who is at risk for serious liver damage is uncertain⁶

The CDC recommends that antiviral hepatitis C treatment should be considered for all HIV patients coinfected with chronic hepatitis C⁷

References:

Salmon-Ceron D et al. Liver disease as a major cause of death among HIV infected patients: role of hepatitis C and B viruses and alcohol. J Hepatol. 2005;42(6):799-805.
Bica I et al. Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis. 2001;32(3):492-497.
Graham CS et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis. 2001;33(4):562-569.
Sulkowski M et al. Presented at: 12th Conference on Retroviruses and Opportunistic Infections; February 22-25, 2005; Boston, MA. Abstract 121.
Soto B et al. Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. J Hepatol. 1997;26(1):1-5.
Marcellin P et al. Fibrosis and disease progression in hepatitis C. Hepatology. 2002;36(5 suppl 1):S47-S56.
Centers for Disease Control and Prevention. Viral hepatitis C. http://www.cdc.gov/ncidod/diseases/hepatitis/c/plan/HCV_infection.htm. Accessed September 21, 2007.

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INDICATIONS

PEGASYS, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously 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) and patients with HIV disease that is clinically stable (eg, antiretroviral therapy not required or receiving stable antiretroviral therapy).

PEGASYS is indicated for the treatment of adult patients with HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation.

Boxed WARNINGS and additional IMPORTANT SAFETY INFORMATION

Alpha interferons, including PEGASYS^® (Peginterferon alfa-2a), 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.

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 a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.

CONTRAINDICATIONS

PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS or any of its components, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment. PEGASYS is also contraindicated in hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment. PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is 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, in women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).

AVOIDING PREGNANCY

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 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. If pregnancy should occur during treatment or during 6 months post-therapy, the patient must be advised of the significant teratogenic risk of COPEGUS therapy to the fetus. Healthcare providers and patients are strongly encouraged to immediately report any pregnancy in a patient or partner of a patient during treatment or during 6 months after treatment cessation to the Ribavirin Pregnancy Registry at 1-800-593-2214.

WARNINGS

Serious adverse events in hepatitis B and hepatitis C trials included neuropsychiatric disorders (homicidal ideation, suicidal ideation, suicide attempt, suicide, psychotic disorder and hallucinations), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, supraventricular arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, psoriasis, lupus, rheumatoid arthritis and interstitial nephritis), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis), pancreatitis, ophthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema), and peripheral neuropathy (in combination with telbivudine).

Adverse reactions reported during post-approval use of PEGASYS therapy, with and without ribavirin, include dehydration, hearing impairment, hearing loss, serious skin reactions, including erythema multiforme major, infections (bacterial, viral and fungal), and serous retinal detachment, and pure red cell aplasia.

MOST COMMON ADVERSE EVENTS

The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials 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%). The adverse event profile of coinfected patients treated with PEGASYS and COPEGUS was generally similar to that shown for monoinfected patients. Events occurring more frequently in coinfected patients were neutropenia (40%), anemia (14%), thrombocytopenia (8%), weight decrease (16%) and mood alteration (9%). In clinical trials of 48-week treatment duration, the adverse event profile of PEGASYS in chronic hepatitis B was similar to that seen in chronic hepatitis C PEGASYS monotherapy use, except for exacerbations of hepatitis. The most common adverse events reported for PEGASYS, observed in clinical studies, were pyrexia (54%), headache (27%), myalgia (26%), fatigue (24%), alopecia (18%) and anorexia (16%).

WARNINGS SPECIFIC TO HEPATITIS C PATIENTS

Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS. Cirrhotic CHC patients coinfected with HIV receiving highly active antiretroviral therapy (HAART) and interferon alfa-2a with or without ribavirin appear to be at increased risk for the development of hepatic decompensation compared to patients not receiving HAART. During treatment, patients’ clinical status and hepatic function should be closely monitored, and PEGASYS treatment should be immediately discontinued if decompensation (Child-Pugh score >6) is observed. Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alfa-based therapies, including PEGASYS. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made and a causal relationship between interferon alfa-based therapies and these events is difficult to establish.

WARNINGS SPECIFIC TO HEPATITIS B PATIENTS

Exacerbations of hepatitis during hepatitis B therapy are not uncommon and are characterized by transient and potentially severe increases in serum ALT. Patients experiencing ALT flares should receive more frequent monitoring of liver function. PEGASYS dose reduction should be considered in patients experiencing transaminase flares. If ALT increases are progressive despite reduction of PEGASYS dose or are accompanied by increased bilirubin or evidence of hepatic decompensation, PEGASYS should be immediately discontinued.

Please see full Prescribing Information, including Boxed WARNINGS for additional Important
Safety Information.

Hepatitis C and HIV Coinfection

Patients with HCV/HIV coinfection: a unique population with rapid progression of liver disease