FINAL RESULTS OF THE PYRAMID 1 STUDY, A PHASE 3 REGISTRATIONAL TRIAL OF RAVIDASVIR (PPI-668) AND SOFOSBUVIR IN HCV GENOTYPE-4 PATIENTS: HIGH RATES OF SUSTAINED VIRAL CLEARANCE IN CIRRHOTIC AND NON-CIRRHOTIC PATIENTS
Author(s): ,
Gamal Esmat
Affiliations:
Cairo University,Cairo,Egypt
,
Maissa El Raziky
Affiliations:
Cairo University,Cairo,Egypt;,Cairo Fatemic Hospoital,Cairo,Egypt
,
Asmaa Gomaa
Affiliations:
National Liver Institute,Cairo,Egypt
,
Tamer Elbaz
Affiliations:
Cairo University,Cairo,Egypt
,
Mahmoud Abouelkhair
Affiliations:
Cairo University,Cairo,Egypt;,Cairo Fatemic Hospoital,Cairo,Egypt
,
Alyaa Sabry
Affiliations:
National Liver Institute,Cairo,Egypt
,
Hadeel Gamel El Deen
Affiliations:
Cairo University,Cairo,Egypt
,
Mohamed Ashour
Affiliations:
Cairo University,Cairo,Egypt;,Cairo Fatemic Hospoital,Cairo,Egypt
,
Mohammed Abdel-Hamid
Affiliations:
Minia University,Cairo,Egypt
,
Ola Nada
Affiliations:
Ain Shams University,Cairo,Egypt
,
Sherine Helmy
Affiliations:
Pharco Pharmaceuticals,Alexandria,Egypt
,
Hanaa Abdel-Maguid
Affiliations:
Pharco Pharmaceuticals,Alexandria,Egypt
,
Richard Colonno
Affiliations:
Presidio Pharmaceuticals,San Francisco,United States
,
Nathaniel Brown
Affiliations:
Presidio Pharmaceuticals,San Francisco,United States
,
Eric Ruby
Affiliations:
Presidio Pharmaceuticals,San Francisco,United States
,
Pamela Vig
Affiliations:
Presidio Pharmaceuticals,San Francisco,Egypt
Imam Waked
Affiliations:
National Liver Institute,Cairo,Egypt
EASL LiverTree™. Colonno R. Apr 16, 2016; 126017
Topic: Efficacy
Ms. Richard Colonno
Ms. Richard Colonno

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Abstract
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SAT-161

Topic: Hepatitis C - clinical (therapy)

Background and aims
HCV genotype-4 (G4) comprises 90% of HCV infections in Egypt. Recent studies with DAAs have often shown suboptimal rates of sustained virologic response (SVR) in cirrhotic patients. We report a Phase 3 trial of ravidasvir (RDV), a pan-genotypic HCV NS5A inhibitor, plus sofosbuvir (SOF), a nucleotide HCV inhibitor, in 300 Egyptian patients (43% with cirrhosis).

Methods
Patients were 18-65 yr with HCV-G4 infection, HCV RNA >4 log10 IU/mL, without decompensated cirrhosis or other liver disease. Three patient groups were enrolled: interferon (IFN)-naïve non-cirrhotic and cirrhotic, by Fibroscan & FIB-4 score (Group 1); IFN-experienced non-cirrhotic (Group 2); and IFN-experienced cirrhotic (Group 3). Groups 1 and 2 were treated QD with RDV 200 mg + SOF 400 mg for 12 wk, randomized 1:1 to added RBV or no RBV. Group 3 received RDV+SOF+RBV, randomized 1:1 to 12 vs. 16 wk treatment. The primary endpoint is SVR12, defined as non-detectable HCV RNA (<12 IU/mL) by the Abbott Real-Time™ PCR assay at 12 wk post-treatment.

Results
300 patients were enrolled (150 in Group 1, 80 in Group 2, and 70 in Group 3); 170 were non-cirrhotic and 130 (43%) were Childs A cirrhotics. At the time of this abstract all patients have completed treatment-period evaluations, and only 31/300 have not yet completed their SVR12 evaluation. Treatment has been well tolerated, with 1 serious adverse event possibly related to treatment (transient bradycardia). HCV RNA declined rapidly and was undetectable by Wk 8 in all patients. For the 264 patients who have reached their SVR12 evaluation point, 164/164 (100%) non-cirrhotic patients and 94/100 (94%) cirrhotic patients achieved SVR12. There have been no viral breakthroughs. All 6 treatment failures have been post-treatment relapses in cirrhotics receiving 12 wk treatment (1 had only 8 wk). Five patients discontinued unrelated to study treatment.

Conclusions
Overall per protocol, 98% of 264 patients achieved SVR12 with SOF+RDV+/-RBV treatment, with SVR12 in all non-cirrhotic patients and failures limited to 6 relapses in cirrhotic patients. RBV did not improve responses in non-cirrhotics or IFN-naïve cirrhotics. All (100%) 20 patients in Group 3 cirrhotics treated for 16 wk have achieved SVR12 (data pending on another 15), suggesting that 16 wk treatment may be sufficient for optimizing viral clearance in IFN-experienced G4 cirrhotics, the most refractory patients. Final study data will be available at the Congress.

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