Epclusa® (SOF/VEL)

Use in Hepatocellular Carcinoma

This document is in response to your request for information regarding the use of Epclusa® (sofosbuvir/velpatasvir [SOF/VEL]) in patients with hepatocellular carcinoma (HCC).

Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.

The full indication, important safety information, and boxed warnings are available at:
www.gilead.com/-/media/files/pdfs/medicines/liver-disease/epclusa/epclusa_pi.

Clinical Study Data on Use of SOF/VEL in HCC

Randomized Controlled Trial of SOF/VEL in HCC1

Study design and demographics

A prospective, randomized controlled trial compared the 1-year RFS of participants with HCV‑related HCC who received a 12-week regimen of SOF/VEL after successful radiographic ablation (with participants whose DAA therapy was postponed for ≥12 months after tumor ablation (postponed DAA group). Enrolled participants (N=84) had 1 to 3 lesions that measured ≤5 cm with no extra-hepatic or vascular involvement and were not candidates for liver resection or transplant. Participants with CP Class B also received RBV or, if they could not tolerate RBV, extended treatment to 24 weeks. Prior DAA exposure or locoregional treatment for HCC, presence of hepatitis B surface antigen, CP Class C, and INR >1.5 were among the exclusion criteria.

Table 1. Baseline Demographics and Disease Characteristics (Kamal et al)1

Results

In the SOF/VEL group, the SVR12 rate was 86.1% (37/43). There were no HCV relapses. At 1 year of follow-up, the overall RFS rate was significantly greater in the SOF/VEL group than in the postponed DAA group (P<0.001; Table 2).

Table 2. Tumor Recurrence and Liver Health at 1-Year Follow-up (Kamal et al)1

aP=0.001. bP=0.01.

There were 6 deaths in the SOF/VEL group (4 due to HCC and 2 due to liver failure) and 5 in the postponed DAA group (4 due to HCC and 1 due to liver failure). Kaplan-Meier estimates of 1-year overall survival rates were 85.8% and 87.6%, respectively. Vascular invasions developed in 3 participants in the SOF/VEL group and 1 participant in the postponed DAA group. There were no lymphatic or distant metastases.

Multivariate analysis showed that lower HCC recurrence 1 year after ablation was significantly associated with receipt of SOF/VEL (HR, 0.4; 95% CI: 0.189–0.846; P=0.016) and higher albumin levels at baseline (HR, 0.161; 95% CI: 0.058–0.453; P=0.001).

Real-World Data on Use of SOF/VEL in HCC

Taiwanese Registry Analysis2

Study design and demographics

Real-world safety data were evaluated in 7677 patients who registered in a Taiwanese HCV registry from August 2019 to August 2021 and who received ≥1 dose of a 12-week regimen of SOF/VEL (68.1%) or an 8- to 12-week regimen of GLE/PIB (31.9%). Patients were followed for ≥3 months after the end of therapy.

Baseline characteristics were not presented according to treatment regimen. Overall, patients were a mean of 59.6 years old, and 53% were male. At baseline, 283 patients (3.7%) had HCC.

Results

The SVR12 rate was 92.8% (7128/7677) in the overall population (per protocol, 99.1%; 7128/7188). Grade 2 to 4 laboratory abnormalities in levels of ALT, AST, or total bilirubin occurred in 146 patients (1.9%) overall, with presence of HCC a significant risk factor (P<0.01) in the overall population (Table 3), in the SOF/VEL-treated patients (multivariate OR, 2.76; 95% CI: 1.3–5.84; P<0.01), and in the GLE/PIB-treated patients (multivariate OR, 2.38; 95% CI: 1.08–5.25; P=0.03). Presence of HCC was also reported as a significant risk factor for Grade 2 to 4 abnormalities of total bilirubin in the overall population (P<0.01) and in the GLE/PIB-treated patients (multivariate OR, 2.51; 95% CI: 1.12–5.61; P=0.03), but not in the SOF/VEL-treated patients; no such relationship was identified for individual evaluations of ALT or AST abnormalities.  

Table 3. Rates and Risk Factors for Grade 2 to 4 Laboratory Abnormalities (Yu et al)2,3

aP<0.01, GLE/PIB vs SOF/VEL, regardless of HCC.

bP<0.01, HCC vs no HCC in overall population.

cNot significant, GLE/PIB vs SOF/VEL, regardless of HCC.

dNot significant, HCC vs no HCC in overall population.

eP<0.01, GLE/PIB vs SOF/VEL.

Of the patients who developed Grade 3 to 4 laboratory abnormalities in ALT, AST, or total bilirubin levels, the number of patients with and without HCC were 0 and 7, respectively, in the SOF/VEL cohort and 1 and 10 in the GLE/PIB cohort. Although presence of HCC was not a significant risk factor, treatment with GLE/PIB vs SOF/VEL was associated with the development of Grade 3 or 4 laboratory abnormalities in ALT, AST, or total bilirubin levels (multivariate OR, 3.77; 95% CI: 1.45–9.78; P=0.01).

South Korean Study4

Study design and demographics

A real-world study was conducted to evaluate the efficacy and safety of SOF/VEL in 37 patients with HCV who were considered difficult to treat due to prior DAA failure, decompensated cirrhosis, or presence of HCC.

Table 4. Baseline Demographics and Disease Characteristics (Woo et al)4

Abbreviations: ASV=asunaprevir; BOC=boceprevir; DCV=daclatasvir; LDV=ledipasvir.

Results

The SVR12 rate in the ITT population was 97.2% (36/37), and the per-protocol SVR12 rate was 100% (36/36). One patient died during treatment due to HCC progression. Most patients tolerated treatment with SOF/VEL well and did not experience adverse events.

CP=Child-Pugh
DAA=direct-acting antiviral
GLE=glecaprevir
HCC=hepatocellular carcinoma
HR=hazard ratio
OR=odds ratio
PIB=pibrentasvir
RBV=ribavirin
RFS=recurrence-free survival
SOF=sofosbuvir
SVR12=SVR 12 weeks after end of treatment
VEL=velpatasvir
 

References

1. Kamal A, Metawea M, Omar H, Ghallab M, Kassem A, Naguib H. Hepatitis C Virus-Related One-Year Hepatocellular Carcinoma Recurrence After Directly Acting Antivirals: A Randomized Controlled Trial. J Gastrointest Cancer. 2024;55(2):913-923.

2. Yu ML, Tai CM, Mo LR, et al. An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan. Hepatol Int. 2024;18(2):461-475.

3. Yu ML, Tai CM, Mo LR, et al. An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan [Supplementary Materials]. Hepatol Int. 2024;18(2):461-475.

4. Woo HY, Heo J, Park YJ. Real-life effectiveness and safety of sofosbuvir/velpatasvir in difficult to treat hepatitis C patients [Abstract FRI392]. Journal of Hepatology. 2022;77(S1):S586.

Product Label

For the full indication, important safety information, and boxed warning(s), please refer to the Epclusa US Prescribing Information available at:
www.gilead.com/-/media/files/pdfs/medicines/liver-disease/epclusa/epclusa_pi.

Follow-Up

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