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Technivie Regimen Shows Good Response Rate for People with HCV Genotype 4

An interferon-free combination of paritaprevir, ritonavir, and ombitasvir -- the drugs in AbbVie's recently approved Technivie coformulation -- taken for 12 weeks cured more than 90% of patients with hepatitis C virus (HCV) genotype 4 in the PEARL-I trial, according to a study report in the June 20 edition of The Lancet.

AbbVie's Viekira Pak or "3D" regimen -- containing the HCV NS3/4A protease inhibitor paritaprevir, a ritonavir booster, and the NS5A inhibitor ombitasvir coformulated in a single pill, packaged with the HCV NS5B polymerase inhibitor dasabuvir as a separate pill -- was approved in the U.S. for the treatment of HCV genotype 1 in December 2014.

Dasabuvir does not work against HCV genotype 4 -- which accounts for about 13% of hepatitis C infections worldwide -- so Christophe Hézode from Hôpital Henri-Mondor/Université Paris-Est and fellow investigators with the PEARL-I study evaluated a simpler "2D" regimen consisting of the paritaprevir coformulation, with or without ribavirin, taken without dasabuvir for 12 weeks.

Last month the U.S. Food and Drug Administration approved the paritaprevir coformulation alone -- branded as Technivie -- for people with HCV genotype 4. In Europe, the coformulation (Viekirax) and dasabuvir (Exviera) have always been sold separately.

The Phase 2b PEARL-I trial (NCT01685203) included 135 genotype 4 chronic hepatitis C patients in France, Hungary, Italy, Poland, Romania, Spain, Turkey, and the U.S. About two-thirds were men and most were white. Fewer than 10% had advanced liver fibrosis, but this trial did not include people with cirrhosis.

Previously untreated participants in this open-label trial were randomly assigned to receive the 2D regimen either with (n=42) or without (n=44) weight-based ribavirin for 12 weeks. All 49 treatment-experienced patients took the 2D regimen with ribavirin for the same duration.

The primary study endpoint was a sustained virological response, or continued undetectable HCV RNA (<25 IU/mL) at 12 weeks after completion of treatment (SVR12). Findings were previously reported in part at the 2014 AASLD Liver Meeting.

Results

• For previously untreated participants, SVR12 rates were 100% in the ribavirin-containing arm and 91% in the ribavirin-free arm -- not a statistically significant difference.
• All treatment-experienced patients achieved SVR12, for a cure rate of 100%.
• In the ribavirin-free treatment-naive group, 1 participant (2%) experienced viral rebound while on therapy and 2 people (5%) relapsed after completing treatment.
• Treatment with the 2D regimen was generally safe and well-tolerated.
• No participants discontinued treatment early due to adverse events.
• The most common side effect was headache (33% of treatment-naive and 29% of treatment-experienced patients).
• 4 people (4%) receiving ribavirin required dose reduction due to anemia or hemoglobin >100 g/L.

Based on these findings, the study authors concluded, "An interferon-free regimen of ombitasvir plus paritaprevir plus ritonavir with or without ribavirin achieved high sustained virological response rates at 12 weeks after the end of treatment and was generally well tolerated, with low rates of anemia and treatment discontinuation in non-cirrhotic previously untreated and previously treated patients with HCV genotype 4 infection."

8/12/15

Reference

C Hézode, T Asselah, KR Reddy, et al. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. The Lancet 385(9986):2502-2509. June 20, 2015.