May 15, 2015
The aim of the study was to find out if shortening the treatment duration to 4 or 6 weeks in certain genotype 1 patients was possible. There were 3 study drugs: GS-9857; Sofosbuvir plus GS-5816 (one-pill).
There were 4 arms in the study:
Most were male (47 to 80%), 50 to 59yo; White (80 to 93%); genotype 1a: 73 to 93%; Arm 4 was prior DAA failure group -- 17 of 30 cirrhotic.
The Bottom Line: The treatment-naive patients without cirrhosis and with cirrhosis who were treated for 6 weeks had cure rates of 93% (Arm 2) and 87% (Arm 3).
The 4 week group only had a 27% (Arm 1) cure rate and the prior DAA treatment failure group with and without cirrhosis had a cure rate of 67% (Arm 4). The most common side effects were nausea, headache, fatigue, and diarrhea.
Editorial Comment: The six-week treatment-naive with and without cirrhosis groups had respectable cure rates and a low side effect profile. It would be interesting to know if pushing the treatment for another 2 weeks would increase the cure rates even higher. Those in the 4-week group or the 6-week group who were prior DAA failures did not perform well. For these patients longer treatment durations or additional drugs will be needed to increase the effectiveness.
The advent of direct-acting antiviral medications means that more patients with decompensated cirrhosis pre- and post-transplant can now be treated. It has been slow in coming but more and more HCV patients are being treated. The study was divided into two groups. There was a total of 329 patients of whom 14 were genotype 4. The remainder were genotype 1:
Group 1. The current study evaluated genotype 1 and 4 patients with more mild disease (mild disease-severe fibrosis (F0-F3) after a liver transplant (post). The patients included treatment-naive and treatment-experienced.
There were 168 post-transplant patients treated in this group.
Group 2. The second study group had more advanced disease pre- and post-transplant. There were 160 patients with decompensated patients in this group (53 post-transplant).
The patients were treated post-transplant with sofosbuvir/ledipasvir plus ribavirin for 12 weeks (78 patients) or 24 weeks (82 patients).
The Bottom Line: The cure rates were 95% and 98% in group #1 and 85% and 88% in group #2. The side effects were generally considered safe and well tolerated especially in a patient population that is considered a difficult one. There were no differences in cure rates between treatment durations of 12 vs. 24 weeks. Although genotype 4 patients were included there were too few patients for to draw any concrete conclusions (14 patients).
Editorial Comment: These are very encouraging results for a patient population that is in need of more treatment options that have fewer side effects to reduce complications and improve quality of life.
Merck's grazoprevir plus elbasvir (once daily) is currently in phase 3 clinical trials for the treatment of hepatitis C in patients with genotypes 1 through 6 -- a pangenotypic drug. The treatment duration is 12 weeks. The current study included genotype 1a and 1b patients who were treated for 12 weeks. There were 234 patients who were treated immediately or whose treatment was deferred. Treatment duration for all of the patients was 12 weeks. The patients were either stage 4 or stage 5 kidney disease (stage 5 kidney disease is the most severe stage of kidney disease). In the study, approximately 80% had stage 5 kidney disease. About 75% were on dialysis (filtering of the kidneys). The patients were evenly divided between Whites/Blacks and mostly were male.
The Bottom Line: The overall cure rate was 99%. There were no differences in cure rates based on cirrhosis, HCV subtype (1a/1b), having diabetes, or being treatment-naive or treatment -experienced. The most common side effects were headache, nausea, fatigue, insomnia, dizziness, and diarrhea.
Editorial Comment: It doesn't get any better than this in a group of patients in the highest need of treatment. This combination has been granted Breakthrough Therapy Designation by the Food and Drug Administration (FDA) for kidney impairment. This means that it will most likely be approved by the FDA early next year. The combination of grazoprevir and elbasvir is co-formulated into one pill, taken once a day.
In this study, there was a total of 421 genotype 1, 4, and 6 treatment-naive (cirrhotic and non-cirrhotic) patients treated for 12 weeks. A little more than one-half were male, mostly White, aged ~53 yo, 63 to 70% HCV RNA>800,000 IU/m.
The Bottom Line: The cure rates by genotype: Genotype 1a: 92% (144 of 157 pts); Genotype 1b: 99% (129 of 131 pts); Genotype 4: 100% (18 of 18 pts); Genotype 6: 80% (8 of 10 pts).
Editorial Comment: The cure rates, side effects and one pill a day make this an attractive new therapy for 2016. It is important to note that the FDA Breakthrough Therapy Designation has been awarded to grazoprevir/elbasvir for genotype 4, but I suspect that studies are needed with more genotype 4 patients. The combination of grazoprevir and elbasvir is co-formulated into one pill, taken once a day.
Sources: Clinical Care Options, Company Press Releases, NATAP, HIVandHepatitis
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