Faldaprevir safe and effective in HCV treatment-experienced patients

Triple therapy including the investigational hepatitis C virus (HCV) protease inhibitor faldaprevir is a safe and effective treatment for people who did not respond to a previous course of HCV treatment, results of a study presented to The Liver Meeting 2013, the  64th annual meeting of the American Association for the Study of Liver Diseases (AASLD), show. Almost three-quarters (70%) of people who had relapsed after a previous course of HCV therapy had a successful treatment outcome, as did half of individuals with a previous partial response and 33% of individuals who had a null response to earlier therapy.

Faldaprevir has performed well in a number of clinical studies involving people with HCV genotype 1 who have not previously taken treatment. The investigational protease inhibitor is taken once daily at a dose of 240mg and studies have examined its safety and efficacy when taken in combination with standard HCV therapy – pegylated interferon and ribavirin – or all-oral regimens compared to standard therapy.

Investigators wished to assess the safety and efficacy of faldaprevir plus pegylated interferon and ribavirin in people who had not responded to a previous course of standard HCV therapy.

They therefore designed a randomised, multi-centre, placebo-controlled trial (STARTVerso3) involving three categories of participants:

• Relapse: people who had undetectable HCV RNA (below 25 copies iu/ml) after 48 weeks of treatment but were detectable within the next 24 weeks of follow-up.
• Partial response: people with a 2 log₁₀ decrease in HCV RNA by week twelve of therapy but who did not have an undetectable viral load at the end of treatment.
• Null response: people without a 2 log₁₀ drop in HCV RNA by week twelve.

A total of 677 people were recruited to the study and their randomisation was according to previous treatment response.All participants in the study received pegylated interferon and ribavirin.

People who had relapsed or had a partial response were randomised into three study arms:

• Placebo.
• Faldaprevir 240mg once daily for twelve weeks and placebo for a further twelve weeks.
• Faldaprevir 240mg once daily for 24 weeks.

All the patients with a previous null response to treatment received faldaprevir and they were randomised into two study arms:

• Faldaprevir 240mg once daily for twelve weeks and placebo for a further twelve weeks.

• Faldaprevir 240mg once daily for 24 weeks.

People with either a previous relapse or partial response who achieved an early treatment response – HCV RNA below 25 copies iu/ml at week four and undetectable at week eight – were eligible to stop therapy at week 24.

The primary endpoint of the study was sustained virologic response (undetectable HCV RNA) twelve weeks after the completion of therapy. Data were also collected on early treatment response rates, sustained virologic response at week 24 and adverse events.

The overall results clearly showed the efficacy of faldaprevir.

Outcomes among people who had previously relapsed showed that 14% of individuals receiving the placebo had a sustained virological response compared to 70% of patients in both the faldaprevir arms (p < 0.0001).

Analysis of participants with a previous partial response showed that 3% of individuals receiving the placebo had a treatment response, compared to 58% of participants who received twelve weeks of therapy with faldaprevir and 47% of individuals who were treated with the drug for 24 weeks (p < 0.0001).

A third of previous null responders had a twelve-week sustained virological response, and treatment outcomes did not differ between the faldaprevir treatment strategies.

Most participants (86 to 87%) with a previous relapse had an early treatment response. Treatment outcomes 24 weeks after the completion of therapy continued to show the benefits of faldaprevir.

None of the common HCV resistance mutations had an impact on the chances of achieving a successful treatment outcome.

Several well-established baseline characteristics were associated with treatment outcomes, and overall response rates were better among people without cirrhosis who had HCV genotype-1b infection and the IL28B-CC polymorphism.

Adverse events were recorded among 95% of participants in the placebo arms and by 97 to 99% of participants randomised to receive faldaprevir. Moderate events occurred in 48% of placebo patients compared to 58 to 59% of individuals treated with the protease inhibitor. Serious adverse events were rare in the placebo arms (1%) but more common among participants in the faldaprevir arms (8 to 10%). However, only 5 to 6% of faldaprevir participants discontinued treatment.

Rates of laboratory abnormalities were similar for the two faldaprevir strategies.

The investigators conclude that the addition of faldaprevir to standard HCV therapy is associated with “clinically meaningful” improvements in treatment outcomes among treatment-experienced patients. Extending the duration of treatment with the drug to 24 weeks did not confer any additional benefits.