In an intent-to-treat
analysis, SVR12 rates in the five arms were as follows:
- BI 207127 TID/ribavirin, 16
weeks: 59%;
- BI 207127 TID/ribavirin, 28
weeks: 61%;
- BI 207127 TID/ribavirin, 40
weeks: 56%;
- BI 207127 BID/ribavirin, 28
weeks: 68%;
- BI 207127 TID, no ribavirin, 28
weeks: 39%.
Stratified by HCV
subtype, people with 1b had higher response rates than those with 1a in all
arms:
- BI 207127 TID/ribavirin, 16
weeks: 1a 38% vs 1b 75%;
- BI 207127 TID/ribavirin, 28
weeks: 1a 44% vs 1b 73%;
- BI 207127 TID/ribavirin, 40
weeks: 1a 47% vs 1b 63%;
- BI 207127 BID/ribavirin, 28
weeks: 1a 43% vs 1b 83%;
- BI 207127 TID, no ribavirin, 28
weeks: 1a 11% vs 1b 57%.
People with the IL28B
CC gene pattern likewise responded better in all arms:
- BI 207127 TID/ribavirin, 16
weeks: non-CC 57% vs CC 67%;
- BI 207127 TID/ribavirin, 28
weeks: non-CC 57% vs CC 71%;
- BI 207127 TID/ribavirin, 40
weeks: non-CC 52% vs CC 68%;
- BI 207127 BID/ribavirin, 28
weeks: non-CC 64% vs CC 79%;
- BI 207127 TID, no ribavirin, 28
weeks: non-CC 33% vs CC 58%.
After subtracting the
patient subgroup with the lowest response
– those with HCV subtype 1a and IL28B
non-CC
– SVR rates for all 1b and 1a CC patients combined were 71, 71, 62,
82 and 53%, respectively. Within this favourable group, viral breakthrough
during treatment occurred in 7, 11, 19, 9 and 29%, respectively. In the
same group, relapse after completing treatment occurred in 10, 2, 0, 2 and
8%, respectively.
Patients with both HCV
genotype 1a and IL28B non-CC had substantially higher breakthrough and relapse
rates, with breakthrough reaching 64% in the BID arm and 91% in the no-ribavirin
arm.
The tested regimens
were generally well tolerated overall. Discontinuation rates due to adverse
events in the five treatment arms were 5, 13, 25, 8 and 11% respectively.
Photosensitivity, skin
rash and jaundice were more common in the BI 207127 thrice-daily arms, with
very few or no cases in the twice-daily arm. The regimen had a minimal effect
on red blood cell count and no effect on white blood cell or platelet counts.
Based on these
findings, the researchers concluded that "the interferon-free combination
of BI 201335 + BI 207127 + ribavirin demonstrated high efficacy and a good
safety profile".
The 600mg
twice-daily dosing schedule for BI 207127 was both more effective and better
tolerated than thrice-daily dosing. Ribavirin was still needed to enable
sustained response. People with HCV subtype 1b and IL28B CC had significantly
higher cure rates
– an interesting finding since IL28B is known to be
associated with interferon responsiveness.
Among patients
treated with BI 207127 three times daily, duration of treatment did not have much
effect on efficacy, suggesting that 16 weeks might also be feasible with
twice-daily dosing. Boehringer Ingelheim is planning further studies of favourable
patients (all 1b and 1a CC) using the BID dose.