Back HCV Treatment EASL 2013: Direct-acting Antivirals Boost Response to Pegylated Interferon/Ribavirin

EASL 2013: Direct-acting Antivirals Boost Response to Pegylated Interferon/Ribavirin

alt

For people with chronic hepatitis C who cannot wait for all-oral regimens, interferon-based therapy is still a reality. Researchers at the recent EASL International Liver Congress (EASL 2013) presented promising data showing that several experimental direct-acting antiviral agents (DAAs) can significantly improve response rates without reducing tolerability.

The advent of DAAs that target different steps of the HCV lifecycle is rapidly changing the treatment paradigm for chronic hepatitis C. But while many patients and providers await interferon-free regimens, others have progressive liver disease and need treatment now.

Fortunately, they too will soon have options beyond the currently approved HCV protease inhibitors -- boceprevir (Victrelis) or telaprevir (Incivek or Incivo) -- which have difficult dosing regimens and come with side effects of their own.

Most of the promising DAAs now making their way through the development pipeline were first tested as add-ons to pegylated interferon/ribavirin, and results from several such studies were presented in Amsterdam.

EASL congress organizers discussed drug development highlights at a kick-off press conference on April 24, which included some speculation about the future of hepatitis C treatment.

"DAAs are ready for prime time," opined EASL Secretary General Mark Thursz. While boceprevir and telaprevir significantly improve treatment response rates compared with pegylated interferon/ribavirin alone, what's really important about the new candidates is their safety profile.

"We've gotten used to current triple therapy having worse or exacerbated side effect profiles," Thursz said. But the new DAAs "are going to be far better tolerated than existing protease inhibitors," plus "more patients will have shorter treatment, and more, of course, will get cured."

Two DAAs -- Janssen's next-generation HCV protease inhibitor simeprevir (formerly TMC435) and Gilead's HCV polymerase inhibitor sofosbuvir (formerly GS-7977) -- have already been submitted for U.S. Food and Drug Administration approval.

Yet when to treat and when to wait remains a dilemma. Although the balance is shifting, the decision, as always, depends on the individual patient.

"If a patient has early stage [liver disease], lots of physicians are recommending their patients wait," Thursz said. "For those with more advanced disease, treating with the standard of care is probably way to go -- unless they have very advanced disease," in which case they have "significant risk of dying from septic complications" if treated with current triple therapy.

"Interferon is not dead yet -- 12 weeks of an interferon triple regimen is tolerable for a large number of patients," he emphasized. "Many are perfectly happy with that, and it may be better than waiting another year for a suitable all-oral regimen." Within 2 to 4 years, however, "pressure to use all-oral regimens will become overwhelming."

If it's "not quite time to bury interferon yet," boceprevir and telaprevir are "in the sick bay," Thurs concluded. "I imagine that market being completely cannibalized, and if I ask my patients, they will not be sorry about that."

5/15/13

References

GJ Dore, E Lawitz, C Hezode, et al. Daclatasvir combined with peginterferon alfa-2a and ribavirin for 12 or 16 weeks in patients with HCV genotype 2 or 3 infection: COMMAND GT2/3 study. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 1418.

P Ferenci, T Asselah, GR Foster, et al. Faldaprevir plus pegylated interferon alfa-2A and ribavirin in chronic HCV genotype-1 treatment-naive patients: final results from STARTVerso1, a randomised double blind placebo-controlled phase III trial. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam, April 24-28, 2013. Abstract 1416.

H Fontaine, C Hezode, C Dorival, et al. SVR12 rates and safety of triple therapy including telaprevir or boceprevir in 221 cirrhotic non responders treated in the French Early Access Program (ANRS CO20-CUPIC). 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam, April 24-28, 2013. Abstract 60.

I Jacobson, GJ Dore, GR Foster, et al. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatment-naïve patients: results from QUEST-1 a phase III trial.48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 1425.

E Lawitz, D Wyles, M Davis, et al. Sofosbuvir + peginterferon + ribavirin for 12 weeks achieves 90% SVR12 in genotype 1, 4, 5, or 6 HCV infected patients: the NEUTRINO study. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 1411.

M Manns, JM Vierling, BR Bacon, et al. High sustained viral response at 12- and 24-week follow-up of MK-5172 with pegylated interferon alfa-2b and ribavirin (PR) in HCV genotype 1 treatment-naive non-cirrhotic patient. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 66.

M Manns, P Marcellin, F Poordad et al. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatment-naive patients: results from QUEST-2 a phase III trial. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 1413.

M Rodriguez-Torres, A Stoehr, E Gane, et al. Sustained viral response and safety of MK-7009 in cirrhotic treatment-experienced patients with genotype 1 HCV infection who have failed previous pegylated interferon and ribavirin treatment. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 106.

K Rutter, A Ferlitsch, A Maieron, et al. Safety of triple therapy with telaprevir or boceprevir in hepatitis C patients with advanced liver disease – predictive factors for sepsis. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam, April 24-28, 2013. Abstract 65.