The Hepatitis C Treatment Pipeline
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|Table 3. Translating Trial Results Into Clinical Practice: Boceprevir and Telaprevir in Treatment-Experienced Persons
|SVR, partial responders||40-52%||54-59%|
|SVR, null responders||Not studied||29-33%|
|SVR, cirrhosi|| F3 and F4 combined:|
partial responders: 30-46%
null responders: not studied
partial responders: 56%
null responders: 39%
partial responders: 34%
null responders: 14%
|Treatment duration recommended in labeling||For responder-relapsers and partialresponders: 36-48 weeks|
For people with compensated cirrhosis and prior null responders, 48 weeks of treatment are recommended
|For responder-relapsers; 24-48 weeks|
For people with compensated cirrhosis and partial/null responders: 48 weeks
|Discontinuation for treatment failure||20%||~37%|
|Discontinuation for AEs||10%||5-13% during telaprevir dosing|
Prescribing information for boceprevir and telaprevir. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2011/202258lbl.pdf and www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf (accessed May 25, 2011).
Bacon BR, Gordon SC, Lawitz E, et al; HCV RESPOND-2 Investigators. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011 Mar 31;364(13):1207-17.
Zeuzem S, Andreone P, Pol S, et al. REALIZE trial final results: telaprevir-based regimen for genotype 1 hepatitis C virus infection in patients with prior null response, partial response, or relapse to peginterferon/ribavirin (Opening and General Session 1) 46th Meeting of the European Association for the Study of the Liver. Berlin, Germany. March 30-April 3, 2011.
Fig 3. Boceprevir: Treatment-Experienced Algorithm
Data from prior responder-relapsers and partial responders; null responders excluded
Source: Prescribing information for boceprevir.. (Accessed May 25, 2011.)
Fig 4. Telaprevir: Treatment Experienced Algorithm*
* Telaprevir labeling notes that a high proportion of null responders, especially those with cirrhosis, did not achieve SVR and developed drug resistance.
Source: Prescribing information for telaprevir. (Accessed May 25, 2011.)
HCV Protease Inhibitors
Boceprevir and telaprevir have the market to themselves for the next couple of years, but the next generation of HCV protease inhibitors is already nipping at their heels. These drugs offer advantages such as more convenient dosing, activity against other genotypes, and/or against protease resistant virus. Many are being studied in combination with other DAAs, with and without peginterferon, and with or without ribavirin.
Side effects include anemia, neutropenia, thrombocytopenia, photosensitivity, itching, rash, hemorrhoids, dysgeusia, headache, elevated alanine amino transferase (ALT) and bilirubin, jaundice, elevated uric acid and gout, dizziness, nausea, vomiting, and diarrhea.
|Table 4. HCV Protease Inhibitors in Development
|Agent/Sponsor||Phase and Population||Comments|
|Phase II, HCV genotype 1, treatment-naive (PEG-IFN-free studies limited to people with the IL-28B CC genotype)||Once daily; ritonavir boosted; with PEG-IFN/RBV, and combination with ABT-333 (non-nucleoside polymerase inhibitor) plus ribavirin (not open as of May 2011)|
With ABT-072 (non-nucleoside polymerase inhibitor) plus ribavirin
|ACH-2684||Phase I; healthy volunteers followed by HCV genotypes 1 and 3, treatment-naive||Once daily; pan-genotypic activity|
|Phase II, HCV genotype 1, treatment-naive||Once daily dosing; studied with PEG-IFN/RBV|
|Phase III, HCV genotype 1, treatment-naive, and treatment-naive/treatment-experienced (combination study)||Once daily; with PEG-IFN/RBV for 12-48 weeks (treatment-naive)|
With PEG-IFN/RBV for 24-48 weeks (treatment-experienced; not open as of 12 August 2011)
With BI 207127 (non-nucleoside polymerase inhibitor) with or without ribavirin (treatment-naive)
|BMS 650032||Phase II, HCV genotype 1 and 4, treatment naive; genotype 1, treatment experienced||Twice daily; with BMS 914143 (peginterferon lambda) with ribavirin; with or without BMS 790052 (NS5a inhibitor) 16-48 weeks (treatment-naive)|
With PEG-IFN/RBV for 24-48 weeks (treatment-naive, genotypes 1 and 4)
With BMS 790052 (NS5a inhibitor), with or without ribavirin, and quad (PEG-IFN/RBV) prior null responders: HCV genotype 1b only in dual DAA arm
|Phase II; HCV genotype 1, null responders||Twice daily; with PEG-IFN/RBV|
(formerly ITMN-181 /RG 7227)
|Phase I/II, HCV genotype 1, treatment-naive and treatment-experienced||Twice daily; ritonavir boosted; with RG7128 (nucleotide polymerase inhibitor), with or without ribavrin (treatment-naive)|
With PEG-IFNRBV in naive and experienced
With ribavrin, with or without RG7128 (nucleotide polymerase inhibitor), with or without PEG-IFN (partial and null responders)
|Phase II; HCV genotype 1, treatment-naive||Twice daily; with tegobuvir (non-nucleoside polymerase inhibitor), with or without PEG-IFN/RBV|
|Phase II; HCV genotype 1, treatment-naive||Once daily; with PEG-IFN/RBV, with and without tegobuvir (non-nucleoside polymerase inhibitor)|
With GS 5885 (NS5a inhibitor), tegobuvir (non-nucleoside polymerase inhibitor), and ribavirin
With PEG-IFN/RBV, with and without GS 5585 (NS5a inhibitor), IL 28B CC genotype only; 6-24 weeks of treatment. Not open as of 24 August 2011
Glaxo Smith Kline
|Phase I; HCV genotype 1, treatment-naive||With and without ritonavir boosting|
|Phase I, HCV genotypes 1 and 3, treatment-naive and treatment-experienced||Not open as of May 2011|
|Phase I, HCV genotypes 1 and 3; phase II, genotype 1, treatment-naive||Once daily; may be active against resistant virus and across genotypes|
Phase II study will be the first HCV treatment trial with an HCV protease inhibitor (boceprevir) in the control arm
|Phase II in HCV genotype 1, ongoing in treatment-experienced||Twice daily; study completed in treatment-naive; SVR rates were numerically higher than PEG-IFN/RBV + placebo, but the difference was not significant; additional trial in treatment-naive withdrawn| < Prev
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This article was provided by Treatment Action Group and HIV i-Base. It is a part of the publication 2011 Pipeline Report.
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