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Results From Phase 3 REALIZE Study Showed Telaprevir-Based Therapy Significantly Improved SVR (Viral Cure) Rates in People Whose Prior Treatment For Hepatitis C Was Unsuccessful
- All major subgroups achieved significantly higher viral cure rates with telaprevir-based therapy compared to pegylated-interferon and ribavirin: 86% vs. 24% in prior relapsers, 57% vs. 15% in prior partial responders and 31% vs. 5% in prior null responders -
- No clinical benefit was observed in delaying telaprevir therapy by four weeks (lead-in) compared to starting telaprevir, pegylated-interferon and ribavirin simultaneously -
- Safety and tolerability results were consistent with prior Phase 3 studies of telaprevir -
REALIZE also evaluated whether viral cure rates could be further
improved by delaying the start of telaprevir by four weeks, during which
time patients received four weeks of pegylated-interferon and ribavirin
alone (lead-in), compared to a simultaneous start. The data showed no
clinical benefit to a lead-in for people treated with telaprevir-based
combination therapy. Safety and tolerability results were consistent
with results from the prior Phase 3 studies of telaprevir. These data
were presented today at The International Liver Congress™ 2011, 46th
annual meeting of the
"Patients with chronic hepatitis C who undergo re-treatment with
currently available medicines rarely achieve a viral cure and remain at
an increased risk for advancing to more serious liver disease," said
Among those in the simultaneous start arm of REALIZE, 83 percent (121/145) of prior relapsers, 59 percent (29/49) of prior partial responders and 29 percent (21/72) of null responders achieved viral cures compared to 24 percent (16/68), 15 percent (4/27) and 5 percent (2/37), respectively, who received pegylated-interferon and ribavirin. The viral cure rates among those in the lead-in arm were 88 percent (124/141) among prior relapsers, 54 percent (26/48) among prior partial responders and 33 percent (25/75) among prior null responders. In a combined endpoint analysis of the two telaprevir-based treatment arms, 86 percent (245/286) of prior relapsers, 57 percent (55/97) of prior partial responders and 31 percent (46/147) of prior null responders achieved viral cures.
"The REALIZE results are encouraging, especially considering people in
this study had been unsuccessfully treated in the past and many already
had scarring of the liver," said
In this study, 48 percent (316/662) of patients overall had advanced liver fibrosis or cirrhosis (scarring of the liver) and 89 percent (586/662) of patients overall had high amounts of hepatitis C virus (high viral load; HCV RNA ≥ 800,000 IU/mL) upon study entry.
Summary of REALIZE Results
REALIZE is the only Phase 3 hepatitis C study to date of a direct-acting antiviral medicine in development that was designed to evaluate people whose prior treatment was unsuccessful, including those who had a null response. In this study, patients were randomized 2:2:1 to two telaprevir-based treatment arms (simultaneous or lead-in) or a control arm of 48 weeks of pegylated-interferon and ribavirin alone. Patients in the telaprevir treatment arms received a total of 12 weeks of telaprevir-based combination therapy. In the lead-in arm, patients received four weeks of pegylated-interferon and ribavirin followed by telaprevir in combination with pegylated-interferon and ribavirin for 12 weeks followed by 32 weeks of pegylated-interferon and ribavirin alone. For those in the simultaneous start arm, the telaprevir-based combination was followed by an additional 36 weeks of pegylated-interferon and ribavirin alone. The primary endpoint of the REALIZE study was SVR in each of the two telaprevir treatment arms compared to the control arm and for the three groups of people included in the study. The total treatment time for all patients in REALIZE was 48 weeks.
|SVR Results % (n)||
Prior Partial Responders
Prior Null Responders
Simultaneous Start Arm+
*The SVR rates observed were statistically significant when compared with the control arm (p <0.001).
+Simultaneous start: 12 weeks of telaprevir (750 mg, q8h), Pegasys® (PEG, pegylated-interferon alfa-2a) & Copegus® (RBV, ribavirin), followed by 36 weeks of PEG & RBV alone.
++Lead-in: 4 weeks of PEG & RBV alone followed by 12 weeks of telaprevir (750 mg, q8h), PEG & RBV, followed by 32 weeks of PEG & RBV alone. There was no clinical benefit with the use of a four-week lead in with no significant improvement in SVR rates and no significant reduction in virologic failure and relapse rates in the lead-in start arm compared to the simultaneous start arm.
+++Control: 12 weeks of placebo, PEG & RBV, followed by 36 weeks of Peg & RBV alone.
Prior Relapser: Defined as a person whose hepatitis C virus was undetectable at the completion of at least 42 weeks of a prior course of therapy but whose virus became detectable during the follow-up period.
Prior Partial Responder: Defined as a person who achieved at least a 2 log in10 reduction in HCV RNA at week 12, but whose hepatitis C virus never became undetectable by week 24 of a prior course of therapy.
Prior Null Responder: Defined as a person who achieved a less than 2 log10 reduction in HCV RNA at week 12 of a prior course of therapy.
Safety and Tolerability Information for the Phase 3 Studies of Telaprevir
The safety and tolerability results of the telaprevir-based combination regimens were consistent across the Phase 3 studies. The most common adverse events were fatigue, pruritus, nausea, headache, rash, anemia, flu-like symptoms, insomnia and diarrhea with the majority being mild to moderate. Rash and anemia occurred more frequently in the telaprevir-based treatment arms compared to the control group.
Rash was primarily characterized as eczema-like, manageable and resolved upon stopping telaprevir. More than 90 percent of rash was mild to moderate and primarily managed with the use of topical corticosteroids and/or antihistamines. Anemia was primarily managed by reducing the dose of ribavirin.
To optimize each patient's opportunity to achieve viral cure in the Phase 3 studies, sequential discontinuation of the medicines was recommended as a strategy to manage certain adverse events. This strategy allowed patients to continue on pegylated-interferon and ribavirin after stopping telaprevir. Discontinuation of all medicines due to either rash or anemia during the telaprevir/placebo treatment phase was 1 percent to 3 percent in the telaprevir treatment arms.
About the Study
REALIZE was a pivotal Phase 3, randomized, double-blind,
placebo-controlled, global study. The majority of clinical trial sites
Status of Telaprevir Regulatory Applications
The regulatory applications for the approval of telaprevir have been
granted Priority Review by the
About the Telaprevir Development Program
Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE studies. Together, these studies enrolled people with genotype 1 chronic hepatitis C who had not been treated for their disease previously as well as people who had been treated before but did not achieve a viral cure.
Vertex is developing telaprevir in collaboration with Tibotec BVBA and
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1 Approximately 60 percent of people who undergo treatment with an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved medicines for genotype 1 hepatitis C, do not achieve SVR,2,3,4 or viral cure.5 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.6,7
More than 170 million people worldwide are chronically infected with
hepatitis C.5 In
PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.
Special Note Regarding Forward-Looking Statements
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Private Securities Litigation Reform Act of 1995, including statements
regarding (i) the date of the scheduled meeting of the FDA's
Vertex creates new possibilities in medicine. Our team aims to discover, develop and commercialize innovative therapies so people with serious diseases can lead better lives.
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2 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
3 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
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