Eric Lawitz of the Texas Liver Institute presented
results from part B of C-CREST 1 and 2, which together evaluated the
combination in 664 people with HCV genotypes 1, 2 or 3, mostly from North
America and Europe.
About 60% of the study population were men, 90% were
white and the median age was 54 years. About a quarter (27%) had HCV genotype 1
(half with harder-to-treat subtype 1a and half with 1b), 23% had genotype 2 and
51% had genotype 3 – considered the most difficult to treat with DAAs. All
people with genotype 1 and 2 were previously untreated, while 44% of the genotype
3s had been treated with pegylated interferon/ribavirin. Over a third of
participants with each genotype had liver cirrhosis (38% overall) and 3% had co-infection
People with genotype 1 were assigned to take the MK3
regimen without ribavirin for either 8 or 12 weeks. People with genotype 2 and 3
were allocated to receive the co-formulation with or without ribavirin for 8
or 12 weeks, or without ribavirin for 16 weeks. An additional 25 people with genotype 3 received MK3 plus ribavirin for 16 weeks.
The primary study endpoint was sustained virological
response, or continued undetectable HCV RNA at 12 weeks after completing
In an intention-to-treat analysis that included all
participants, SVR12 rates were 93% for people with genotype 1a treated with MK3
alone for 8 weeks and 98% for those treated for 12 weeks. Cure rates were 98%
and 100%, respectively, for those with genotype 1b.
Among people with genotype 2, cure rates were 86% for
MK3 with or without ribavirin taken for 8 weeks, 97% for 12 weeks and 100% for
16 weeks. Among those with genotype 3, SVR12 rates were 95% for the 8-week
regimen, 97% for 12 weeks and 96% for 16 weeks.
Cure rates were high and similar for people with or
without cirrhosis in all genotype groups; all but two people with cirrhosis
achieved SVR12 in a per-protocol analysis. In the genotype 2 and 3 analysis,
SVR12 rates were similar with or without ribavirin – and in fact the lowest
rate (83%) was seen in the genotype 2 group treated with ribavirin for 8 weeks.
In the genotype 3 analysis, SVR12 rates were similar for treatment-naive and
treatment-experienced participants receiving 8, 12 or 16 weeks of therapy.
There were three relapses among people with genotype 1
and seven among people with genotype 2 treated for 8 weeks, but none among those
receiving the 12-week regimen. Among people with genotype 3, however, relapses
occurred after 8, 12 or 16 weeks of therapy (4, 3 and 2 cases, respectively).
Among people with genotype 1, the presence of
resistance-associated variants (RAVs) at baseline did not impair treatment
efficacy. Among people with genotype 2, with the L31M RAV at baseline, the cure
rate fell to 80% when treated for 8 weeks but was 100% when treated for 12
weeks. Among those with genotype 3, with the Y93H RAV, cure rates were lower with
both 8 and 12 weeks of treatment (50% and 71%, respectively), although the
number of these participants was small.
Treatment was generally safe and well tolerated, with two
drug-related serious adverse events (worsening chronic obstructive pulmonary disease [COPD] and depression due to
ribavirin) and one discontinuation due to drug-related adverse events (fatigue
and malaise). The most common adverse events were headache (22%), fatigue (19%)
and nausea (13%).
There was one case of reinfection with a different
HCV strain in an individual who had reached SVR8.
Based on these findings, the researchers concluded
that MK-3682/grazoprevir/ruzasvir for 8 or 12 weeks was highly effective for
people with HCV genotype 1, while 12 or 16 weeks was effective for people with genotype 2, and 8, 12 or 16 weeks was effective for those with genotype 3. Adding
ribavirin did not increase SVR12 rates.
Dr Lawitz noted that all genotype 3
treatment-experienced people with cirrhosis – the hardest group to treat –
were cured using MK3 without ribavirin for 12 or 16 weeks (the only relapser
was on the most intensive 16-week regimen
He also reported that all
but one of the 23 people with HIV/HCV co-infection achieved SVR12, but the single individual who was re-infected was co-infected.