Basel, Switzerland � April 15, 2004 � New data from two pioneering hepatitis C (HCV) studies with PEGASYS^� plus COPEGUS^� will be presented this week at the 39^th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin.  The multinational trials � one in patients with HIV-HCV co-infection and the other in HCV patients with persistently normal levels of alanine aminotransferase (ALT) �demonstrate that PEGASYS plus COPEGUS is an effective, safe and predictable treatment option.

Final results of APRICOT report highest ever treatment response in co-infected patients

The final results of APRICOT (AIDS PEGASYS^� Ribavirin International CO-infection Trial) � the largest and only multinational study evaluating the efficacy and safety of pegylated interferon combination therapy in people co-infected with HIV and HCV � found that the combination of PEGASYS and COPEGUS achieved a 40% sustained virological response (SVR) � the highest ever reported in a trial of co-infected patients.

�APRICOT provides the guidance that we have wanted on how best to treat co-infected patients and there is no doubt that the combination of PEGASYS and COPEGUS represents the best we can currently offer this patient population,� said Dr. Francesca Torriani, Associate Professor of Medicine, Antiviral Research Centre, University of California at San Diego and one of the APRICOT lead investigators. �What�s more, we now have data from this trial on our ability to confidently predict as early as week 12 of therapy which patients are likely to achieve a sustained virological response.�

The key APRICOT findings that Dr. Torriani will present on Sunday, April 18^th are:[i]

• 40% of patients treated with PEGASYS plus COPEGUS achieved an SVR compared to 20% of patients treated with PEGASYS monotherapy and 12% of patients treated with conventional interferon/ribavirin.
• Genotype 1 patients treated with PEGASYS plus COPEGUS achieved a four-fold increase in SVR compared to conventional interferon/ribavirin (29% vs 7%).
• 62% of genotype 2/3 patients treated with PEGASYS plus COPEGUS combination therapy achieved an SVR compared to 20% with conventional interferon/ribavirin.

New APRICOT data identifies patients most likely to respond

New data will be presented on APRICOT that will help physicians identify those patients with the best chance of achieving an SVR.  71% of co-infected patients achieved an EVR following 12 weeks of a fixed 180mg/week dose of PEGASYS and 800mg daily of COPEGUS (ribavirin), and of those, more than half (56%) achieved an SVR.  Among patients with the more difficult-to-treat HCV genotype 1, 45% who had an EVR went on to achieve a sustained virological response.[ii]  The ability to tell patients at week 12 if their treatment is likely to generate an SVR, is now recognized as having an important role in the motivation of patients to start with, and stay on, therapy.

Real world patient population in APRICOT

The patients in this landmark study were predominantly male, middle-aged with stable HIV disease.  However, patients had a wide range of HIV status; the majority were on anti-retroviral therapy and they had very high HCV viral loads (10-15 million copies/ml).  The very low (12%) response achieved by patients to the arm receiving conventional interferon combination therapy is illustrative of the challenging nature of the co-infection present in these patients.

European Union contributes nearly half the patients

422 of the 868 patients randomized in APRICOT came from 11 European Union countries � a total of 19 countries participated. These patients were randomized to receive either PEGASYS 180mg once weekly plus COPEGUS 800mg daily; PEGASYS 180mg monotherapy once weekly (plus placebo COPEGUS tablets), or conventional interferon alfa-2a 3MIU three times a week in combination with ribavirin 800mg daily, all for 48 weeks.

New data on quality of life from second landmark trial in patients with  normal ALT

A substantial proportion of hepatitis C patients have �normal� levels of ALT (an enzyme present in the blood used historically as a marker for liver injury and disease).  Because these levels are �normal�, these patients were traditionally considered to have �mild� hepatitis and therefore did not need to be treated.  More recently, however, there has been a growing awareness that ALT is actually a poor marker of liver disease.  Indeed, all patients in this trial had evidence of liver inflammation and nearly one third had some degree of fibrosis.

In the only global trial in this group of patients, 514 patients were randomized to receive either PEGASYS 180mg once weekly plus COPEGUS 800mg daily for either 24 or 48 weeks, followed by a 24-week treatment-free follow-up period.  A third arm was an untreated control group, since no treatment was considered the standard of care at the time the study was designed. 

The key trial findings were:[iii]^,[iv]

�         Overall 52% of hepatitis C patients with �normal� ALT levels achieved an SVR while none in the control arm did. These results are consistent with the excellent results seen in other patient populations treated with PEGASYS plus COPEGUS.

�         72% of PEGASYS patients infected with genotypes 2 or 3 who were treated for 24 weeks and 40% of PEGASYS patients infected with the �difficult-to-treat� genotype 1 who were treated for 48 weeks achieved an SVR.

New data presented at EASL noted that:

�         Those who achieved an SVR reported a better QoL including reduced fatigue than both the untreated control group and those who failed to achieve an SVR.

�         Those patients who failed to achieve an EVR following 12 weeks of therapy were highly unlikely to achieve an SVR.  As in other HCV patient groups, this provides an early and meaningful time point for physicians and patients to discuss the benefits of continuing with treatment if viral eradication may not be achieved.

�The results of this trial are very important because until now it was not clear if there were benefits to treating these patients � which account for about 30% of patients with chronic hepatitis C,� said Professor Stefan Zeuzem, from Saarland University, Homburg, Germany.  �Now, we know these patients can be effectively treated like other patients with hepatitis C and experience improvements in their quality of life.�

New trial underway by Roche in another difficult-to-treat group of patients

Recently Roche announced the launch of the first global trial to study the efficacy of PEGASYS plus COPEGUS in another difficult-to-treat patient population: hepatitis C patients who failed to respond to peginterferon alfa-2b plus ribavirin combination therapy. This trial is known as REPEAT, which stands for "REtreatment with PEGASYS in pATients not responding to prior peginterferon alfa-2b/ribavirin combination therapy".  The REPEAT study will evaluate  the efficacy and safety of the combination of PEGASYS and COPEGUS given for a longer, 72-week period, as well as examining the role of an induction regimen in this treatment- resistant population. 

Close to 1,000 patients will participate in this study from Europe, North America and Latin America.

About PEGASYS

PEGASYS, a new generation hepatitis C therapy that is different by design, provides significant benefit over conventional interferon therapy in patients infected with HBV and HCV.  The benefits of PEGASYS are derived from its new generation large 40 kilodalton (KD) branched-chain polyethylene glycol (PEG) construction, which allows for sustained drug levels over the course of a full week.  PEGASYS also distributes more readily to the liver (the primary site of infection) than conventional interferon.  In HCV PEGASYS provides superior efficacy compared to conventional interferon combination therapy in HCV patients of all genotypes.  PEGASYS is the only pegylated interferon available as a ready-to-administer solution.  Each weekly subcutaneous injection contains 180mcg of pegylated interferon alfa-2a (40KD) which is the approved dose for all patients, regardless of body weight.

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