Results from studies in chronic hepatitis C patients with HIV-1 co-infection and liver transplant recipients
AbbVie has announced results from studies in chronic hepatitis C patients with human immunodeficiency virus type 1 (HIV-1) co-infection (TURQUOISE-I) and liver transplant recipients (CORAL-I) at The Liver Meeting®2014.
New, detailed results from part one of the Phase 2 portion of AbbVie’s Phase 2/3 open-label study, TURQUOISE-I, showed patients co-infected with genotype 1 (GT1) hepatitis C virus (HCV) and HIV-1 receiving AbbVie’s investigational treatment and ribavirin (RBV) for 12 weeks or 24 weeks achieved sustained virologic response rates 12 weeks post-treatment (SVR12) of 93.5 percent (n=29/31) and 90.6 percent (n=29/32), respectively. These data were presented November 11, as a “Poster of Distinction.”
“Patients living with both chronic HCV and HIV have been historically considered more difficult to treat,” said Barry Bernstein, M.D., vice president, infectious disease development, AbbVie. “TURQUOISE-I is one of the few dedicated studies looking specifically at this population, who are seen in everyday clinical practice. These data will help us gain a better understanding of how our investigational treatment works in this subpopulation of genotype 1 patients.”
Additionally, results from the first cohort of AbbVie’s ongoing open-label Phase 2 study, CORAL-I, were presented during an oral session and published online in The New England Journal of Medicine. Results showed that non-cirrhotic liver transplant patients with recurrent GT1 HCV and new to treatment after transplantation achieved a SVR12 rate of 97.1 percent (n=33/34) and a sustained virologic response rate 24 weeks post-treatment (SVR24) of 97.1 percent (n=33/34) after 24 weeks of treatment.
“Recurrence of HCV infection in the new graft post-liver transplantation is universal in those that have the virus prior to transplantation, and can be associated with an aggressive disease course,” explained Dr. Paul Kwo, medical director of liver transplantation and professor of medicine, Indiana University School of Medicine. “The high SVR rates seen in CORAL-I are promising and offer valuable information as we continue to assess this regimen within this specific patient population.”
TURQUOISE-I is an ongoing Phase 2/3, multi-center, randomized, open-label study evaluating the efficacy and safety of AbbVie’s all-oral, interferon-free investigational treatment combining three direct-acting antivirals (ombitasvir/ABT-450/ritonavir and dasabuvir) with RBV (weight based dosing of 1000 mg or 1200 mg per day divided twice daily) for 12 or 24 weeks in adult patients with chronic GT1 HCV infection with or without compensated liver cirrhosis who are also infected with HIV-1. Study patients were either new to therapy (treatment naïve) or had failed previous treatment with pegylated interferon and RBV (treatment-experienced), had a stable immune status (CD4+ counts of ?200 cells/mm3 or CD4+ % ?14%) and had HIV-1 ribonucleic acid levels suppressed on a stable atazanavir- or raltegravir-based antiretroviral HIV therapy.
No patients discontinued treatment due to adverse events in either the 12-week or 24-week arm. In the 12-week arm, no virologic breakthroughs were observed while on treatment. One patient (3.3 percent) experienced post-treatment relapse after 12 weeks of treatment. In the 24-week treatment arm, one virologic breakthrough was observed (3.1 percent). Two patients in the 24-week treatment group were believed to have been re-infected post-treatment by a different strain of HCV than the original infection. The most commonly reported adverse events (greater than 15 percent in both treatment arms combined) were fatigue (47.6 percent), insomnia (19 percent), nausea (17.5 percent), and headache (15.9 percent). Elevations in total bilirubin were the most common laboratory abnormality (68.3 percent), were mainly composed of indirect bilirubin, and were not associated with aminotransferase elevations. Reductions in RBV dose because of anemia or reduced hemoglobin occurred in 9.5 percent of patients (n=6/63); all six patients achieved SVR12.
CORAL-I is an ongoing Phase 2, multi-center, two-cohort, open-label study evaluating the efficacy and safety of AbbVie’s all-oral, interferon-free investigational treatment combining three direct-acting antivirals (ombitasvir/ABT-450/ritonavir and dasabuvir) with RBV (RBV dosing left up to the discretion of the investigator) for 24 weeks in adult non-cirrhotic (screening biopsy Metavir score ?F2) liver transplant recipients with recurrent chronic GT1 HCV infection. Patients in the study initiated therapy at least 12 months after receiving a liver transplant, had not received other HCV therapy since their liver transplant, and were on a stable immunosuppressant regimen based on either tacrolimus or cyclosporine, for which dose adjustments were advised. Enrollment in the second cohort of the study is ongoing.
One patient (2.9 percent) discontinued the study due to adverse events but still achieved SVR12. Two patients experienced serious adverse events. The most commonly reported treatment-emergent adverse events (greater than 20 percent) were fatigue (50 percent), headache (44.1 percent), cough (32.4 percent), anemia (29.4 percent), diarrhea (26.5 percent), insomnia (26.5), asthenia (23.5 percent), nausea (23.5 percent), muscle spasms (20.6 percent), and rash (20.6 percent). No patients experienced virologic breakthrough while on treatment; however, one patient experienced post-treatment relapse. Nine patients had a grade 2 reduction in hemoglobin, and one patient had a grade 3 reduction. Five patients with hemoglobin decreases (anemia) received a medication to boost their red blood cell production at the investigator’s discretion. No patients discontinued study drugs because of anemia, required a blood transfusion, or experienced a rejection of their transplanted liver.
An Interferon-free Antiviral Regimen for HCV after Liver Transplantation, Paul Y. Kwo, M.D., Parvez S. Mantry, M.D., Eoin Coakley, M.D., Helen S. Te, M.D., Hugo E. Vargas, M.D., Robert Brown, M.D., M.P.H., Fredric Gordon, M.D., Josh Levitsky, M.D., Norah A. Terrault, M.D., M.P.H., James R. Burton, M.D., Wangang Xie, Ph.D., Carolyn Setze, M.S., Prajakta Badri, Ph.D., Tami Pilot-Matias, Ph.D., Regis A. Vilchez, M.D., Ph.D., and Xavier Forns, M.D., The New England Journal of Medicine, DOI: 10.1056/NEJMoa1408921, published 11 November 2014.