Pegasys (peginterferon alfa-2a) - 2 indications

Scroll down for more information on each indication:

• for the treatment of hepatitis C as combination or monotherapy in adults and as combination for pediatrics 5 yrs and older; approved October 2002
• for the treatment of chronic hepatitis B in adults and pediatrics; approved in 2005

General Information

Pegasys (peginterferon alfa-2a) is an inducer of the innate immune response.

Pegasys is specifically indicated for the following:

Chronic Hepatitis C (CHC)

• Adult Patients: In combination therapy with other hepatitis C virus drugs for adults with compensated liver disease. PEGASYS monotherapy is indicated only if patient has contraindication or significant intolerance to other HCV drugs.
• Pediatric Patients: In combination with ribavirin for pediatric patients 5 years of age and older with compensated liver disease

Chronic Hepatitis B (CHB)

• Adult Patients: Treatment of adults with HBeAg-positive and HBeAgnegative chronic hepatitis B (CHB) infection who have compensated liver disease and evidence of viral replication and liver inflammation
• Pediatric Patients: Treatment of non-cirrhotic pediatric patients 3 years of age and older with HBeAg-positive CHB and evidence of viral replication and elevations in serum alanine aminotransferase (ALT)

Pegasys is administered by subcutaneous injection. Scroll sown for recommended dosing for each indication.

Mechanism of Action

Pegasys is produced when interferon alfa-2a undergoes the process of pegylation in which one or more chains of polyethylene glycol (also known as PEG) are attached to another molecule. In Pegasys, a large, branched, mobile PEG is attached to the interferon alfa-2a molecule, providing a selectively protective barrier against rapid absorption, metabolism and elimination. At the same time, the PEG maintains the ability of the interferon alfa-2a to attack the virus.

Side Effects

In clinical studies, the following adverse events were reported most often:

• Headache
• Fatigue
• Myalagia
• Pyrexia
• Rigors
• Arthralgia
• Nausea
• Alopecia
• Injection-site reaction
• Neutropenia
• Insomnia
• Depression
• Anorexia
• Irritability

The Pegasys drug label comes with the following Black Box Warning: Pegasys may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor closely and withdraw therapy with persistently severe or worsening signs or symptoms of the above disorders.

Indication 1 - for the treatment of hepatitis C as combination or monotherapy in adults and as combination for pediatrics 5 yrs and older

approved October 2002

Dosing/Administration

In adult patients with CHC, Pegasys is dosed as 180 mcg per week and the duration of treatment depends on indication, genotype, and whether it is administered with other HCV antiviral drug

In pediatric patients with CHC, Pegasys is dosed as 180 mcg/1.73 m2 x BSA per week, in combination with ribavirin, and the duration of treatment depends on genotype

Clinical Trial Results

Three pivotal phase III clinical studies of Pegasys demonstrated that the sustained virological response (defined as undetectable serum hepatitis C RNA levels post-treatment [on or after study week 68]) in the Pegasys treated subjects was as high as 38% in the overall population versus 19% in the interferon alfa-2a group. Subjects with cirrhosis who were treated with Pegasys showed a sustained virological response as high as 30% versus 8% in the interferon alfa-2a group. Subjects with genotype 1 treated with Pegasys showed showed a sustained virological response of up to 23%, compared to 6% in the interferon alfa-2a group.

In addition, studies indicated that it can be determined at week 12 of treatment whether a subject is unlikely to attain a sustained virological response with Pegasys. This could prevent subjects from continuing a therapy to which they will most likely be unresponsive.

Indication 2 - for the treatment of chronic hepatitis B in adults and pediatrics

approved in 2005

Dosing/Administration

In adult patients with CHB, Pegasys is dosed as 180 mcg per week for 48 weeks

In pediatric patients with CHB, Pegasys is dosed as 180 mcg/1.73 m2 x BSA per week for 48 weeks

Clinical Trial Results

The two large-scale multinational phase III trials, in more than 1,500 patients with both the HBeAg-positive and HBeAg-negative variations of chronic hepatitis B, demonstrated that 24 weeks after a defined 48 week period of therapy, more patients achieved a sustained response with Pegasys than with lamivudine. These studies demonstrated that the addition of lamivudine to Pegasys did not improve response rates over Pegasys alone.
 
Specifically, hepatitis B patients treated with Pegasys had higher rates of:

• HBV seroconversion in HBeAg positive patients (32% Pegasys vs. 19% lamivudine) 
• HBV DNA response (32% Pegasys vs. 22% lamivudine in HBeAg positive patients and 43% Pegasys vs. 29% lamivudine in HBeAg negative patients)
•  ALT normalization in HBeAg negative patients (59% Pegasys vs. 44% lamivudine)