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[DewDiligence]

Roche Reports Pegasys Data in Second-Line HCV

[In patients who failed to respond to PegIntron+ribavirin in the first-line setting, extending Pegasys+ribavirin second-line treatment from the usual 48 weeks to 72 weeks increased SVR from 8% to 16%. However, using a double-dose of Pegasys during the initial 12 weeks of second-line therapy had no significant effect on SVR, regardless of the duration the treatment. In a separate study of Peg-Intron in the second line, the SVR rate was 23% (#msg-23123038); however, that study included relapsers as well as non-responders and hence is not comparable to the Pegasys study reported here.]

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Treatment with PEGASYS(R)/COPEGUS(TM) Provides Hope for Hepatitis C Patients Whose Infection Did Not Initially Respond to Peg-Intron/Ribavirin

http://biz.yahoo.com/prnews/071102/nyf002.html?.v=68

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Friday November 2, 8:30 am ET

- Response at 12 weeks is a powerful predictor of eventual treatment success -

BOSTON, Nov. 2 /PRNewswire/ -- Roche today announced final results from the REPEAT study, which demonstrated that treatment with once-weekly PEGASYS® (peginterferon alfa-2a) and daily COPEGUS(TM) (ribavirin) for 72 weeks is a promising treatment option for patients whose infection did not respond to previous treatment with another pegylated interferon (Peg- Intron®, peginterferon alfa-2b) and ribavirin. Further, the results showed that response at 12 weeks was a powerful predictor of the eventual outcome: the majority of patients with undetectable virus at 12 weeks went on to achieve a sustained virological response (SVR) after 72 weeks of treatment, while few patients with detectable virus at 12 weeks achieved SVR. These data were presented in an oral session at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), being held in Boston, Nov. 2-6.

"One of the greatest areas of need in hepatitis C today is to find solutions for patients who have not seen treatment success with an initial course of therapy. REPEAT is an important study which adds significantly to our knowledge about how to manage these patients, demonstrating that extending treatment with PEGASYS and COPEGUS is a promising option," said Donald Jensen, M.D., Professor of Medicine and Director of the Center for Liver Diseases at the University of Chicago Hospital in Chicago, and lead investigator in REPEAT. "A significant finding from REPEAT is confirmation of the reliability of using a patient's response at 12 weeks as a predictor of treatment success, even in patients with cirrhosis. This means that patients who achieve undetectable virus at 12 weeks can continue treatment with a good likelihood of success. It also means that clinicians can confidently discontinue treatment in patients who do not achieve an early response."

More About the REPEAT Study

Enrolling 950 patients from Europe, North America and Latin America, REPEAT (REtreatment with PEgasys in pATients Not Responding to Peg-Intron Therapy) was designed to explore whether intensified treatment with a higher fixed-dose induction of PEGASYS in combination with COPEGUS and/or longer treatment duration may increase treatment success rates in patients who didn't respond to at least twelve weeks of Peg-Intron/ribavirin combination therapy. Patients were randomized 2:1:1:2 to one of four regimens:

-- Patients in arms A (n=318) and B (n=158) received PEGASYS 360 mcg/week [double the normal dose] for 12 weeks, followed by 180 mcg/week for a further 60 or 36 weeks respectively [i.e. 72 or 48 weeks of treatment in all]

-- Patients in arms C (n=158) and D (n=316) received PEGASYS 180 mcg/week [the normal dose] for 72 or 48 weeks, respectively

-- All patients received COPEGUS (1,000/1,200 mg/day) in combination with PEGASYS

Results showed:

-- The primary endpoint was met: SVR, defined by undetectable hepatitis C virus RNA in the blood six months after the end of treatment, was significantly higher for arm A (16 percent) compared to arm D (nine percent)

-- A pooled analysis of the 72-week arms vs. the 48-week arms showed that 72 weeks of treatment had the biggest impact on success of treatment, with a doubling of SVR rate compared to 48 weeks (16 percent vs. eight percent). A pooled analysis of the induction dose arms vs. standard dose arms showed that treatment with higher fixed-dose induction for this difficult-to-treat patient population did not provide significant additional benefit

-- Response at 12 weeks was a strong predictor of successful treatment

-- Of patients whose virus was undetectable after 12 weeks of therapy, 57 percent in the 72-week arms went on to achieve treatment success (by comparison, among patients who still had detectable virus after 12 weeks, only four percent achieved treatment success)

-- The proportion of patients with undetectable virus at 12 weeks was 17 percent

"REPEAT exclusively enrolled patients who had not previously responded to pegylated interferon combination therapy, in this case Peg-Intron and ribavirin," continued Dr. Jensen. "These patients are a more difficult-to- treat group than relapsers and those who did not respond at all to treatment with non-pegylated interferons, either alone or with ribavirin. For this reason, results from REPEAT cannot be meaningfully compared to results from trials with a large proportion of patients who were relapsers or who did not respond to treatment with older interferons."

The incidence and types of adverse events and serious adverse events were generally consistent across all the arms, and the frequency of moderate to severe hematologic effects were broadly similar across all arms. Discontinuations for adverse events and lab abnormalities were higher for extended treatment. Patients with cirrhosis had a somewhat higher incidence of adverse events, premature withdrawals and dose modifications. (Please see below for complete safety information about PEGASYS and COPEGUS).
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