Real-world evidence on sofosbuvir/velpatasvir for hepatitis C infection

Prof. Ming-Lung Yu
Kaohsiung Medical University
Taiwan
15 Nov 2021
Real-world evidence on sofosbuvir/velpatasvir for hepatitis C infection
While the global response against hepatitis C virus (HCV) infection in the last three decades is widely regarded as a success, the epidemic is far from over and the WHO has recently updated targets for HCV elimination by 2030. At a webinar organized by Hong Kong Association for the Study of Liver Diseases (HKALD), Professor Ming-Lung Yu of the Kaohsiung Medical University, Taiwan, shared his experience in treating HCV in the real-world (RW) setting, with particular emphasis on the benefits of sofosbuvir/velpatasvir (SOF/VEL) in treating chronic hepatitis C (CHC) infection.

EASL 2020 guidelines

To improve access to HCV treatment and increase global cure rate, the European Association for the Study of the Liver (EASL) 2020 guidelines recommend using simplified, genotyping/subtyping-free, pan-genotypic direct-acting antiviral (DAA) drug combinations, such as a 12-week course of the once-daily single-tablet regimen (STR) SOF/VEL, for HCV-monoinfected or HCV-HIV coinfected patients with CHC without cirrhosis or with compensated (Child-Pugh A) cirrhosis, including treatment-naïve patients and prior interferon treatment-experienced patients. [J Hepatol 2020;73:1170-1218; Epclusa Hong Kong Prescribing Information]

Taiwan experience with SOF/VEL in HCV

The Taiwan Association for the Study of Liver (TASL) HCV Registry (TACR) was set up in 2017 and includes 30,278 HCV-infected patients across 48 study sites, who are receiving DDA therapy (eg, SOF/VEL) under the National Health Insurance. Prior to enrolment, 92.0 percent of the participating patients were treatment-naïve. [Liver Int 2021;41:1265-1277; ML Yu, et al, GEST 2021; Pwu RF, et al, International Symposium on Viral Hepatitis and Liver Disease – Global Hepatitis Summit 2021]

“One of TACR’s objectives is to evaluate treatment outcomes, with the goal of achieving the WHO target by 2025,” said Yu. “Almost all [99.5 percent] of SOF/VEL-treated patients achieved sustained virological response [ie, undetectable HCV RNA level at 12 weeks after end-of-treatment (EOT); SVR12] and of the 50 SOF/VEL-treated patients with decompensated liver cirrhosis [LC], 70.0 percent showed improved Child-Pugh score at the end of follow-up compared with baseline.” [Yu ML, et al, Gastroenterology Society of Taiwan (GEST) 2021 Annual Meeting]

HK-GIL-031md_01

In one retrospective study (n=191), HCV-infected patients with stage 4/5 chronic kidney disease (CKD) (stage 5, 67.0 percent) treated with SOF/VEL (400/100 mg/day) with or without low-dose ribavirin (RBV; 200 mg/day) achieved an SVR12 of 100 percent. A numerical improvement in estimated glomerular filtration rate (eGFR) was observed at SVR12 vs baseline (27.0 mL/min/1.73 m2 vs 25.5 mL/min/1.73 m2; p=0.06) among those with stage 4 CKD not receiving dialysis. [Gut 2021;doi:10.1136/gutjnl-2020-323569]

Another study, which included data from two prisons and TACR (n=2,478), reported an SVR12 of 95.6–100 percent among SOF/VEL-treated patients with HCV genotype (GT) 3 infection (n=109; persons who inject drugs [PWID] and prisoners, 37.6 percent). [Chen CT, et al, Taiwan Digestive Disease Week 2020, abstract P.037; Hsu WF, et al, GEST 2021, abstract P.015; Cheng PN, et al, Global Hepatitis Summit 2021, abstract 204]

A single-cohort study (n=195) comparing the effectiveness of SOF/VEL in HCV-infected patients with vs without GT 6 showed similar SVR12 between the two groups (100 percent vs 99.4 percent). [Chen JJ, et al, GEST 2021, abstract P038]. SVR12 (100 percent) was comparable to that observed in another single-cohort study in prisoners (n=129; PWID, 72.0 percent; GT 6, 44.20 percent). [WF Hsu, et al, GEST 2021, abstract P.015]

Consistently high SVR12 (98.0 percent) was also reported with SOF/VEL with or without low-dose RBV in HCV-infected patients with hepatocellular carcinoma in another single-cohort study (n=50; hepatic decompensation, n=11), along with a substantial reduction in alanine aminotransferase at SVR12 vs baseline (54.09 U/L vs 223.00 U/L) among those with decompensated cirrhosis at SVR12. [Huang YH, et al, GEST 2021, abstract P.046]

“The US FDA recently issued a safety warning regarding the rare occurrence of worsening liver function or liver failure associated with the use of protease inhibitor [PI]–containing regimens, such as glecaprevir/pibrentasvir [GLE/PIB], elbasvir/grazoprevir [ELB/GRZ] and sofosbuvir/velpatasvir/voxilaprevir [SOF/VEL/VOX], in HCV patients with moderate-to-severe liver impairment [ie, Child-Pugh B–C],” said Yu. [https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-occurrence-serious-liver-injury-use-hepatitis-c-medicines-mavyret-zepatier-and] “SOF/VEL with and without RBV, on the other hand, is the only pan-genotypic DAA drug combination for patients with Child-Pugh B–C HCV-related cirrhosis, with SVR12 of 100 percent demonstrated in a retrospective study in 107 patients with Child-Pugh B–C decompensated cirrhosis.” [Clin Mol Hepatol 2021;27:575-588]

“Furthermore, a single-cohort study in 98 HCV-infected patients with prior liver transplantation showed higher SVR12 in patients treated with SOF/VEL with or without RBV [100 percent vs 93 percent] compared with those treated with either SOF plus ledipasvir/daclatasvir [LDV/DCV] or SOF plus LDV/DCV plus RBV,” noted Yu. [Ke CK, et al, GEST 2021, abstract P.050]

AEs and drug-drug interactions with SOF/VEL

Lower rates of adverse events (AEs), such as pruritus (2.9 percent vs 17.4 percent), abdominal discomfort (4.4 percent vs 5.8 percent), dizziness (4.2 percent vs 2.0 percent), and total bilirubin elevation (ie, 1.5–3 x ULN) (2.9 percent vs 5.3 percent) were reported in patients treated with SOF/VEL vs glecaprevir/pibrentasvir (GLE/PIB) in a real-world study (n=1,356) in Taiwan. [Sci Rep 2021;11:13543]

In Hong Kong, a territory-wide registry cohort study on drug-drug interactions (DDIs) between DAAs (SOF/VEL, 25.9 percent) and comedications in 2,981 HCV-infected patients (mean age, 59 years; male, 60.6 percent) showed a high prevalence (70.3 percent) of comedications (ie, used within 4 weeks prior to and during DAA therapy). Simvastatin (7.1 percent), atorvastatin (2.7 percent), and tacrolimus (1.9 percent) were the most common comedications with potential category 3 interactions that could lead to contraindications. [Au CL, et al, The Asian Pacific Digestive Disease Week (APDW) 2021, abstract OPP-0045]

MinMon programme: Simplified minimal monitoring approach

The phase IV, multinational, open-label, prospective, single-arm Minimal Monitoring (MiniMon) study included 399 HCV-infected patients (female, 35 percent), of which 42 percent, 34 percent and 9 percent had HIV-1 coinfection, compensated cirrhosis, and were either former or current PWID, respectively. All patients received 84 tablets of SOF/VEL (400/100 mg QD) STR and fibrosis-4 score assessment at study entry, with no pretreatment genotyping and scheduled on-treatment clinics or laboratory assessment. Vast majority of study patients were contacted remotely at week 4 (99 percent) and week 22 (84 percent), while 3.8 percent recorded 21 unplanned visits due to abnormal laboratory values at baseline, non-AE clinical events or AEs. [Solomon S, et al, AASLD 2020]

“Results of the MinMon study showed that a simplified, minimal monitoring approach to HCV treatment with a 12-week course of SOF/VEL was as effective [in achieving an overall SVR12 of 95.0 percent] and safe [AE rate, 5.8 percent; serious AE rate, 3.5 percent] as current clinical standards in treatment-naïve HCV-infected patients without decompensated liver cirrhosis,” said Yu.

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