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ALLY-1: transplant patients, those with cirrhosis achieve SVR12 with daclatasvir, sofosbuvir
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VIENNA — A regimen containing Sovaldi and daclatasvir was associated with favorable 12-week sustained virologic response rates in a cohort of patients with advanced cirrhosis, according to data presented at the 2015 International Liver Congress.
“This 12-week pangenotypic regimen of daclatasvir, sofosbuvir and ribavirin is generally safe, well-tolerated and efficacious across multiple genotypes,” Fred Poordad, MD, of the Texas Liver Institute and University of Texas Health Science Center in San Antonio, said during the Late Breakers session.
Poordad and colleagues conducted an open-label study that included 60 patients with advanced cirrhosis and 53 post-transplant patients. They treated patients for 12 weeks with 400 mg Sovaldi (sofosbuvir, Gilead), 60 mg daclatasvir (Bristol-Myers Squibb) and 600 mg ribavirin, initially. Ribavirin dose was adjusted when necessary.
Twelve extra weeks of treatment was offered to patients who underwent transplantation during therapy.
Forty percent of the cirrhotic cohort and 42% of those in the post-transplant group were treatment-naive. Of the patients enrolled, three-quarters had genotype 1 disease.
The overall SVR12 rate was 83% among patients with cirrhosis and 94% in the transplant group. Among patients with genotype 1 disease, 82% of those with cirrhosis and 95% of post-transplant patients reached SVR12. A regression analysis determined that sex, age, IL28B status and viral load had no impact on SVR, according to Poordad.
Patients with cirrhosis and genotype 1a disease experienced a 76% SVR12 rate, compared with 100% of patients with genotype 1b and cirrhosis. For the transplant group, 97% of genotype 1a patients and 90% of genotype 1b patients reached SVR12. Patients were not stratified to have equal representation of Child-Pugh A, B and C within each genotype or subtype. Additionally, this regimen showed success in genotype 3 with 83% of those with cirrhosis and 91% of those post-transplant patients achieving SVR.
“This ALLY-1 study demonstrates that 12 weeks of daclatasvir, sofosbuvir and ribavirin yielded high SVR rates in advanced cirrhotic genotype 3 patients as well as post-transplant patients,” Poordad said.
SVR12 was higher among those with Child-Pugh A (92%) and Child-Pugh B (94%) than it was for those with Child-Pugh C (56%). Poordad noted that there was not much change in Child-Pugh A MELD scores. Child-Pugh B had an overall improvement; several patients had a one-point worsening in their MELD score though they reached SVR. Child-Pugh C had the greatest improvement in MELD score and those that worsened also did not achieve SVR.
“What correlates best apparently with Child-Pugh C SVR rate is low albumin. Albumin below 2.8 conferred less likely SVR rates,” Poordad said. “It appears further studies are warranted to define the appropriate Child-Pugh C patient who should be treated, keeping in mind that they did have a decline in their MELD score and this may disadvantage them for opportunities to receive a liver transplant.”
Among 13 patients who failed to reach SVR12, 12 relapsed after treatment was completed (nine with cirrhosis and three post-transplant). Poordad showed that among the failures, only four of the patients — all in the cirrhosis group — showed NS5A resistance-associated variants (RAVs) at baseline. At failure, all 13 patients showed emergent RAVs.
There were four patients in the cirrhosis group who underwent transplantation during therapy. All four reached SVR12.
Headache, fatigue, anemia, diarrhea and nausea were the most commonly reported adverse events. No serious treatment-related events were reported. – by Rob Volansky and Katrina Altersitz
For More Information:
Poordad F, et al. Abstract L08. Presented at: International Liver Congress; April 22-26, 2015; Vienna.
Disclosure: Poordad reports receiving grants from Abbvie, Achillion, Bristol-Myers Squibb, Gilead Sciences, Idenix, Janssen, Salix and Theravance; and consulting for Abbvie, Bristol-Myers Squibb, Gilead Sciences, Janssen and Salix.
Editor's note: This article has been updated with clarification from the presenter.