Theme: Clinical Research Year: 2016
EFFICACY AND SAFETY OF SOFOSBUVIR/VELPATASVIR IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION RECEIVING OPIOID SUBSTITUTION THERAPY: ANALYSIS OF PHASE 3 ASTRAL TRIALS
Grebely J1, Dore GJ1, Zeuzem S2, Aspinall R3, Fox R4, Han L5, McNally J5, Osinusi A5, Brainard DM5, Subramanian M5, Carr V6, Foster GR7, Mangia A8, Sulkowski M9, and Feld JJ10
1The Kirby Institute, UNSW Australia, Sydney, NSW, Australia; 2Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany; 3Portsmouth Hospitals NHS Trust, Portsmouth, UK; 4Brownlee Centre, Glasgow, UK; 5Gilead Sciences, Inc., Foster City, California, USA; 6Gilead Sciences, Stockley Park, UK; 7Queen Mary University London, London, UK; 8Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy; 9Johns Hopkins University, Baltimore, Maryland, USA; 10Toronto Centre for Liver Disease, Toronto, Ontario, Canada
Background: HCV infection is highly prevalent among patients with a history of injecting drug use, including those receiving opioid substitution therapy (OST). The Phase 3 ASTRAL studies demonstrated that treatment with the once-daily fixed-dose combination tablet of sofosbuvir/velpatasvir (SOF/VEL) was well-tolerated and results in SVR12 rates >95% across all HCV genotypes. Limited data exists for patients on OST treated with DAAs for HCV.
Methods: This was a post-hoc analysis of data among patients treated with SOF/VEL in the Phase 3 ASTRAL-1, ASTRAL -2, and ASTRAL -3 studies. Records of concomitant mediations were reviewed for use of OST. The safety and efficacy of SOF/VEL were compared between patients receiving, and not receiving OST.
Results: Among 1,035 enrolled, 51 (5%) patients were receiving OST. Compared to those not receiving OST (n=984), those receiving OST were more often male (77% vs. 60%) and had HCV genotype 3 infection (47% vs. 24%). Adherence to ≥90% SOF/VEL was numerically lower in patients receiving OST compared with patients not receiving OST (90% vs. 96%, P=0.06). Overall, the incidence of adverse events (AEs) was similar between those receiving and not receiving OST, although patients receiving OST had a higher incidence of Grade 3 and 4 AEs (14%) compared with non-OST patients (3%). SVR12 was similar in those receiving OST (96%, 49/51) and not receiving OST (98%, 966/984, P=0.26). Two patients did not achieve SVR12 in the OST group (anxiety, headache and attention disturbance, n=1; non-adherence, n=1). One patient not on OST and without a history of drug use and was determined to have HCV re-infection by deep sequencing of virus at time of virologic failure.
Conclusions: The pangenotypic SOF/VEL FDC provides a well-tolerated and highly effective treatment for HCV infection for patients on OST. Further prospective evaluation of SOF/VEL in people who inject drugs (PWIDs) is ongoing.
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