Investor Update
Basel, 27 October 2006
Customising treatment with Pegasys plus Copegus improves chances for cure in Hepatitis C
Results from two clinical trials point to innovative strategies for fast and slow responders to treatment
Higher fixed doses of Pegasys plus Copegus in patients with certain ‘difficult-to-treat’ characteristics may lead to a better chance of cure according to results presented at the 57th annual meeting of the American Association for the Study of Liver Diseases (AASLD).
“We have known for some time that certain patients have ‘difficult-to-treat’ characteristics and improving treatment success rates using currently available medications for these patients is an urgent need,” said Michael W. Fried, M.D., University of North Carolina at Chapel Hill. “If strategies using higher fixed doses of peginterferon alfa-2a and ribavirin are validated in larger studies, these findings give us hope that more patients living with chronic hepatitis C can be cured.”
About the higher fixed dose study
This randomised, double-blind study enrolled 188 adults with previously untreated genotype 1 chronic hepatitis C infection, high blood levels of hepatitis C (hepatitis C RNA level greater than 800,000 IU/ml) and a bodyweight of more than 85 kg. Patients received 48 weeks of treatment with Pegasys at either the standard fixed dose of 180 microg/week or a higher fixed dose of 270 microg/week, plus Copegus at the standard dose of 1200 mg/day or a higher dose of 1600 mg/day, as follows:
• peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 1200 mg/day (Group A)
• peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 1600 mg/day (Group B)
• peginterferon alfa-2a (40KD) 270 microg/week plus ribavirin 1200 mg/day (Group C)
• peginterferon alfa-2a (40KD) 270 microg/week plus ribavirin 1600 mg/day (Group D)
The rate of SVR in patients receiving the most intensive regimen (Group D) was higher than in patients receiving the standard-dose regimen (Group A) at 47 per cent versus 28 per cent. The results also highlight the important role that Copegus plays in achieving an SVR. It was the combination of a higher dose of Pegasys and a higher dose of Copegus, which seemed to act synergistically, resulting in an impressive increase in SVR (difference of 19 per cent) versus the current standard regimen.
The use of higher doses of Pegasys and Copegus was associated with a small increase in the rate of adverse events, although the number of patients stopping treatment early was similar.
A second study presented at AASLD showed that Pegasys ‘super-responders’ have an excellent chance of being cured following a shortened duration of therapy. Over three-quarters of hepatitis C patients with difficult-to-cure genotypes 1 and 4 who had a rapid response to treatment (virus-free at 4 weeks) went on to achieve a sustained virological response (SVR) following only 24 weeks of treatment with Pegasys (peginterferon alfa-2a (40KD)) plus Copegus (ribavirin). An SVR is indicative of a cure.
“These results show that within a month of starting therapy with Pegasys plus Copegus we can give some patients the excellent news that they are highly likely to be cured,” said Dr. Peter Ferenci, lead study investigator and Professor of the Department of Internal Medicine IV, Gastroenterology and Hepatology at the University of Vienna, Austria. “These data could help patients to seek treatment and motivate them to stay on treatment. These results could change the way that patients are treated in the future.”
About the ‘super-responder’ study
In this study, patients received Pegasys 180 microg once weekly plus a 1000-1200 mg daily dose of Copegus. After 4 weeks of treatment, virus levels in the blood were measured to identify the ‘super-responders’. ‘Super-responders’ (patients who were virus-free at week 4) were treated for only another 20 weeks, receiving a total of 24 weeks of therapy. All other patients continued on treatment and were reassessed at week 12. Those who had an early virological response (EVR; undetectable viral load or a drop in viral load to less than one per cent of pre-treatment viral load at week 12) were randomised to receive either 48 or 72 weeks of therapy. Those who did not have an EVR continued treatment for 72 weeks
Results:
• 77 per cent of ‘super-responders’ in the study achieved an SVR.
• Among those who had an EVR, SVR rates were similar (56 per cent of patients treated for 48 weeks achieved an SVR compared with 43 per cent treated for 72 weeks).
• Patients who did not have an EVR were highly unlikely to achieve an SVR (4 per cent) even after 72 weeks of treatment.
“These two clinical trials underscore Roche’s commitment to finding better treatment solutions with Pegasys, the cornerstone of hepatitis C therapy,” said Claire Steers, Pegasys Life Cycle Leader at Roche. “It is this ongoing commitment that has led to Pegasys being indicated for the treatment of hepatitis C in the broadest range of patients, including difficult-to-cure patients such as those with HIV-HCV co-infection and cirrhotic patients.”
About Hepatitis C
Hepatitis C, the most common chronic blood-borne infection, is transmitted primarily through blood or blood products. Hepatitis C chronically infects 170 million people worldwide,
About Pegasys
Pegasys, the market leader worldwide in hepatitis C therapy, provides significant benefit over conventional combination interferon therapy in hepatitis C patients of all genotypes. The benefits of Pegasys are derived from its 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. Pegasys is the only pegylated interferon available as a ready-to-administer solution. Each weekly subcutaneous injection contains 180microg of pegylated interferon alfa-2a (40KD), which is the approved dose for all patients, regardless of body weight.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2005 sales by the Pharmaceuticals Division totalled 27.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.2 billion Swiss francs. Roche employs roughly 70,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet (www.roche.com).
Customising treatment with Pegasys plus Copegus improves chances for cure in Hepatitis C
Results from two clinical trials point to innovative strategies for fast and slow responders to treatment
Higher fixed doses of Pegasys plus Copegus in patients with certain ‘difficult-to-treat’ characteristics may lead to a better chance of cure according to results presented at the 57th annual meeting of the American Association for the Study of Liver Diseases (AASLD).
1
It is well recognised that response rates to treatment can be significantly lower in patients who have several characteristics such as infection with genotype 1, high levels of virus in the blood, and heavy bodyweight.2
The results of a new study show that intensifying treatment with a higher fixed dose of Pegasys along with a higher dose of Copegus could yield significantly higher response rates in these difficult-to-cure patients.“We have known for some time that certain patients have ‘difficult-to-treat’ characteristics and improving treatment success rates using currently available medications for these patients is an urgent need,” said Michael W. Fried, M.D., University of North Carolina at Chapel Hill. “If strategies using higher fixed doses of peginterferon alfa-2a and ribavirin are validated in larger studies, these findings give us hope that more patients living with chronic hepatitis C can be cured.”
About the higher fixed dose study
This randomised, double-blind study enrolled 188 adults with previously untreated genotype 1 chronic hepatitis C infection, high blood levels of hepatitis C (hepatitis C RNA level greater than 800,000 IU/ml) and a bodyweight of more than 85 kg. Patients received 48 weeks of treatment with Pegasys at either the standard fixed dose of 180 microg/week or a higher fixed dose of 270 microg/week, plus Copegus at the standard dose of 1200 mg/day or a higher dose of 1600 mg/day, as follows:
• peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 1200 mg/day (Group A)
• peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 1600 mg/day (Group B)
• peginterferon alfa-2a (40KD) 270 microg/week plus ribavirin 1200 mg/day (Group C)
• peginterferon alfa-2a (40KD) 270 microg/week plus ribavirin 1600 mg/day (Group D)
The rate of SVR in patients receiving the most intensive regimen (Group D) was higher than in patients receiving the standard-dose regimen (Group A) at 47 per cent versus 28 per cent. The results also highlight the important role that Copegus plays in achieving an SVR. It was the combination of a higher dose of Pegasys and a higher dose of Copegus, which seemed to act synergistically, resulting in an impressive increase in SVR (difference of 19 per cent) versus the current standard regimen.
The use of higher doses of Pegasys and Copegus was associated with a small increase in the rate of adverse events, although the number of patients stopping treatment early was similar.
A second study presented at AASLD showed that Pegasys ‘super-responders’ have an excellent chance of being cured following a shortened duration of therapy. Over three-quarters of hepatitis C patients with difficult-to-cure genotypes 1 and 4 who had a rapid response to treatment (virus-free at 4 weeks) went on to achieve a sustained virological response (SVR) following only 24 weeks of treatment with Pegasys (peginterferon alfa-2a (40KD)) plus Copegus (ribavirin). An SVR is indicative of a cure.
“These results show that within a month of starting therapy with Pegasys plus Copegus we can give some patients the excellent news that they are highly likely to be cured,” said Dr. Peter Ferenci, lead study investigator and Professor of the Department of Internal Medicine IV, Gastroenterology and Hepatology at the University of Vienna, Austria. “These data could help patients to seek treatment and motivate them to stay on treatment. These results could change the way that patients are treated in the future.”
About the ‘super-responder’ study
In this study, patients received Pegasys 180 microg once weekly plus a 1000-1200 mg daily dose of Copegus. After 4 weeks of treatment, virus levels in the blood were measured to identify the ‘super-responders’. ‘Super-responders’ (patients who were virus-free at week 4) were treated for only another 20 weeks, receiving a total of 24 weeks of therapy. All other patients continued on treatment and were reassessed at week 12. Those who had an early virological response (EVR; undetectable viral load or a drop in viral load to less than one per cent of pre-treatment viral load at week 12) were randomised to receive either 48 or 72 weeks of therapy. Those who did not have an EVR continued treatment for 72 weeks
3
Results:
• 77 per cent of ‘super-responders’ in the study achieved an SVR.
• Among those who had an EVR, SVR rates were similar (56 per cent of patients treated for 48 weeks achieved an SVR compared with 43 per cent treated for 72 weeks).
• Patients who did not have an EVR were highly unlikely to achieve an SVR (4 per cent) even after 72 weeks of treatment.
“These two clinical trials underscore Roche’s commitment to finding better treatment solutions with Pegasys, the cornerstone of hepatitis C therapy,” said Claire Steers, Pegasys Life Cycle Leader at Roche. “It is this ongoing commitment that has led to Pegasys being indicated for the treatment of hepatitis C in the broadest range of patients, including difficult-to-cure patients such as those with HIV-HCV co-infection and cirrhotic patients.”
About Hepatitis C
Hepatitis C, the most common chronic blood-borne infection, is transmitted primarily through blood or blood products. Hepatitis C chronically infects 170 million people worldwide,
4
with an additional three to four million people newly infected each year. It is a leading cause of cirrhosis, liver cancer and liver failure.About Pegasys
Pegasys, the market leader worldwide in hepatitis C therapy, provides significant benefit over conventional combination interferon therapy in hepatitis C patients of all genotypes. The benefits of Pegasys are derived from its 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. Pegasys is the only pegylated interferon available as a ready-to-administer solution. Each weekly subcutaneous injection contains 180microg of pegylated interferon alfa-2a (40KD), which is the approved dose for all patients, regardless of body weight.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2005 sales by the Pharmaceuticals Division totalled 27.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.2 billion Swiss francs. Roche employs roughly 70,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet (www.roche.com).
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References:
1
Fried M, Jensen D, Rodriguez-Torres M, et al. Improved sustained virological response (SVR) rates
with higher, fixed doses of peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (RBV)(COPEGUS®) in
patients with “difficult-to-cure” characteristics. In: American Association for the Study of Liver Diseases;
2006; Boston, Massachusetts 2006.
2 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon
alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347(13):975-82.
3
Ferenci P, Laferl H, et al. Customizing treatment with peginterferon alfa-2a (40KD) (PEGASYS®)
plus ribavirin (COPEGUS® ) in patients with HCV genotype 1 or 4 infection. Interim results of a prospective
randomized trial.
4 Global surveillance and control of hepatitis C. Report of a
WHO Consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium.
J Viral Hepat 1999;6(1):35-47.