General Information

Pegasys (peginterferon alfa-2a) was approved in October 2002 for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha, including patients with compensated cirrhosis. Pegasys is a pegylated interferon that remains active in the bloodstream longer and at a more constant level than interferon alpha.

Pegasys is available as premixed solution. It is administered at a dose of 180 ug as a subcutaneous injection once a week for a recommended duration of 48 weeks.

Clinical 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.

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

Alpha interferons, including Pegasys, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.

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.

Additional Information

For further information about Pegasys, please visit the Roche web site at www.roche.com.