The only info I have read about the dose change so far has been tied to Vertex gradually declining quarterly performance and how they hope to improve the side effect profile and encourage more people to treat now rather than wait. I am guessing the OPTIMIZE trial shows twice daily dosing is equally efficaceous.
Results of the OPTIMIZE trial, which compared twice daily (BID) versus three times daily (TID) dosing of Incivek, will be presented at the upcoming American Association for the Study of Liver Diseases annual meeting on 12 November. The Phase III, randomized, open-label, international study found BID to be noninferior to TID Incivek in treatment-naive, genotype 1 HCV infected patients, according to the abstract.
Impact of less-frequent dosing
The problem with triple therapy regimens is that, though they produce high response rates, they are also quite burdensome in terms of treatment, given that they are interferon-containing, said Dr Ray Chung, director, Hepatology, Medicine Service, Massachusetts General Hospital. Interferon is dosed as a weekly injection and is associated with flu-like side effects for possibly up to 44 weeks of treatment in a triple therapy regimen.
If a patient can realistically defer treatment, which is true in most cases based on liver disease stage, patients might be better off waiting for new therapies, Chung said. Patients with more advanced disease require treatment more urgently, whereas those with less advanced disease are able to wait.
While a BID dosing schedule is nice, the fundamental cooperative toxicity between interferon, ribavirin and a protease inhibitor must be factored into the mix, Chung added.
BID dosing will not make more patients get treated now, agreed Dr Susannah Naggie, assistant professor of medicine, Infectious Diseases, Duke University. The new regimen will not make a difference for someone who has already decided to wait, she said.
The first patients treated with Incivek were very motivated and did pretty well with the TID regimens, noted Dr Arthur Kim, director, Viral Hepatitis Clinic, Massachusetts General Hospital. For patients still waiting, however, BID dosing is generally not enough of a tipping point to convince them to start therapy now over next generation DAAs, he said.
Even though it has not yet been approved, Dr Eliot Godofsky, infectious disease specialist, University Hepatitis Center, Bradenton, Florida, has already been using the BID regimen in patients where it was thought the Incivek TID regimen would not work. Patients have reported less diarrhea when on the BID regimen, he added, speculating it may be due to the requirement of taking Incivek with a fatty meal. Still, he said, there is likely not enough of a benefit from the BID schedule to sway patients who have already deferred treatment. While BID is better than TID, it is still a complicated regimen, he noted.
Dr Don Jensen, professor of medicine, director, Center for Liver Diseases, University of Chicago, agreed some physicians are likely already using the BID schedule. The BID regimen does make it easier for some patients to manage their therapy, as ribavirin is also dosed BID.
Still, he said, this would likely only help Incivek maintain an advantage over Merck’s (NYSE:MRK) fellow first-generation protease inhibitor, Victrelis (boceprevir), rather than next-generation therapies. Victrelis is similarly administered thrice-daily in combination with interferon and ribavirin.
This would be great since I am in my 5th wk. that is if this is true. I will be asking my doc since it would make things so much easier for me to eat at a better time.
This might be a separate post but...
This does not mean the product labeling or FDA dose recommendations have changed (yet). The HCV protease inhibitor telaprevir (Incivek) taken twice-daily with pegylated interferon plus ribavirin is as likely to produce sustained virological suppression as the approved 3-times-daily schedule, with similar safety and tolerability even for people with advanced liver fibrosis, according to study findings presented last week at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2012) in Boston.
The pivotal trials that supported approval of the HCV protease inhibitors telaprevir and boceprevir (Victrelis) -- the first direct-acting antiviral agents for hepatitis C treatment -- administered both drugs every 8 hours. But this dosing regimen is inconvenient for patients, which may result in missed doses and reduced effectiveness.
Maria Buti from Hospital Vall d'Hebron in Barcelona and colleagues conducted the Phase 3 open-label OPTIMIZE trial comparing telaprevir twice-daily versus every 8 hours, to see if the less frequent dosing schedule is non-inferior to the approved regimen.
OPTIMIZE enrolled 740 ☆☆previously untreated patients☆☆ with Genotype 1 chronic HCV, mostly in North America and Europe. ≈ 60% were men, > 90% were white, and the mean age was 48 years. Nearly 60% had harder-to-treat HCV subtype 1a and about 70% had non-favorable IL28B gene variants. About 30% had advanced liver disease (stage F3-F4), including 14% with cirrhosis.
Participants were randomly assigned (1:1) to received telaprevir either at doses of 750 mg every 8 hours (Q8H) or 1125 mg every 12 hours (BID), both in combination with pegylated interferon alfa-2a (Pegasys) and 1000-1200 mg/day weight-adjusted ribavirin.
★ Similar proportions of participants in the 2 arms -- 73% on Q8H telaprevir and 74% on BID -- achieved sustained virological response 12 weeks after completing treatment (SVR12) in an intent-to-treat analysis.
★ In a per-protocol or as-treated analysis, response rates remained similar, 75% and 76%, respectively.
★ Proportions of patients with rapid virological response (RVR) at week 4 who went on to achieve SVR12 were also similar, 85% and 86%, respectively.
★ On-treatment virological breakthrough rates were the same in both arms.
Response rates did not differ significantly between Q8H and BID dosing for any patient subgroup based on IL28B status or fibrosis stage.
★ For patients with cirrhosis, SVR12 rates were 49% and 54%, respectively.
★ Nearly 100% of people in both study arms experienced some adverse events. However, rates of serious adverse events (9% and 8%, respectively) and adverse events leading to telaprevir discontinuation (19% vs 15%, respectively) were similar in both arms.
★About half of participants in both the Q8H and BID arms developed rash.
★The rate of grade 3 or higher anemia was somewhat higher in the BID arm (19% vs 26%), but the difference was not statistically significant.
"In this study, with a high proportion of patients with bridging fibrosis or compensated cirrhosis, the efficacy of 1125 mg BID telaprevir was non-inferior to 750 mg Q8H, offering the potential of simplified dosing to genotype 1 HCV-infected patients," the researchers concluded. "Safety and tolerability were generally similar between regimens and consistent with the known profile of telaprevir."
Hi ldyllic, I knew they were testing this but admit I have not been following it, my question if you know would be about the side effect of taking 1125 mg at once instead of 750... It seems people here complain a lot about stomach issues, and the burning rear problems.........
I have discussed this issue with my doctor 2 weeks ago. I produced and put in from of him the study you have mentioned and whish was anounced at Boston. He is up to date with absolutely everything and what he told me was: the study has not been validated yet (or something like that - must be a certain phase in a trial when there is a validation process. As a result I started with 2 X 3 as the actual giudlines
Even if official guidlines will change that does not meant that the ones on theraphy already can shift from 2 X 3 to 3 X 2 as nobody knows how that will interfere with results (if in any way). Any of you ready to take that risk?