Gilead Sciences Presents Over 30 New Hepatology Research Findings at APASL 2025, Highlighting Long-Term Efficacy and Safety of TAF, Seladelpar, and Combination Therapies

▎WuXi AppTec Content Team Report

Eight-Year Follow-Up Data in Chinese CHB Patients Show Good Efficacy and Safety of TAF

At this APASL conference, Professor Jinlin Hou, Director of the Department of Infectious Diseases at Nanfang Hospital, Southern Medical University, will deliver an oral report on the 8-year Phase 3 clinical study results of TAF in the Chinese population, which confirmed the efficacy and safety of TAF.

The Phase 3 clinical study of TAF in the Chinese population enrolled a total of 334 patients with CHB. After being randomly assigned (2:1) to receive double-blind treatment with either TAF (25 mg, n=227) or tenofovir disoproxil fumarate (TDF, 300 mg, n=107) for three years, all patients were transitioned to open-label TAF treatment until Year 8. The primary efficacy endpoint was the virological suppression rate at Week 384 in both groups (i.e., the TAF→TAF group and the TDF→TAF group). The safety endpoints included adverse events (AEs) and changes in various bone and renal safety parameters, with bone mineral density (BMD) changes assessed using dual-energy X-ray absorptiometry (DXA) on the hip and spine.

Among 334 CHB patients, 311 entered the open-label phase, with 212 in the TAF-TAF group and 99 in the TDF-TAF group. At week 384, the results using the Missing = Failure (M=F) statistical method showed viral suppression rates of 79.3% (180/227) in the TAF-TAF group and 78.5% (84/107) in the TDF-TAF group (P=0.8517). Meanwhile, the results using the Missing = Exclusion (M=E) statistical method indicated,The virological suppression rates in the two groups were 95.2% (180/189) and 95.5% (84/88), respectively.(P=0.9407). The ALT normalization rates were high in both groups at Week 384 (TAF-TAF group 87.8% vs. TDF-TAF group 84.9%, M=E analysis, P=0.5514; M=F analysis showed a similar trend). Additionally, the TAF-TAF group demonstrated a higher proportion of serological response. Among patients with baseline FibroTest scores, the proportions of improved, unchanged, and worsened liver fibrosis status in the TAF-TAF group were 26.1%, 71.7%, and 2.2%, respectively, while in the TDF-TAF group, they were 28.9%, 61.4%, and 9.6%. No genotypic resistance to TAF was detected during the 8-year follow-up period.

Overall safety data showed that TAF treatment for 8 years had a favorable safety profile. The incidence of grade 3 or higher adverse events was low, with 5.7% (12/212) in the TAF-TAF group and 6.1% (6/99) in the TDF-TAF group, and no discontinuations due to adverse events were reported. Differences in renal function and bone parameters observed between the two groups during the double-blind phase gradually narrowed after receiving open-label TAF treatment. By week 384, the median changes in eGFR from baseline were small and comparable between the two groups (-1.3 mL/min vs -2.0 mL/min, P=0.9233). Additionally, the differences in median percentage changes of RBP:Cr and ꞵ2M:Cr observed between the two groups during the double-blind phase also significantly diminished after switching to open-label TAF treatment. The slight decreases in hip and spine bone mineral density seen with TDF use improved after switching to TAF treatment.

The 8-year follow-up effectiveness data of the study indicateWhether continuing with TAF or switching from TDF to TAF, good antiviral treatment efficacy can be maintained; safety data shows that: long-term TAF treatment has good safety and is well-tolerated, bone and renal safety are effectively maintained, and patients who switch from TDF to TAF show improved bone and renal safety.。

The results of the 8-year follow-up of the Phase 3 clinical study of TAF conducted in China further support the long-term efficacy and safety of TAF as one of the first-line oral antiviral drugs for CHB.

Seladelpar Demonstrates High Efficacy and Safety in Asian PBC Patients

Seladelpar is a treatment for Primary Biliary Cholangitis (PBC).Novel Selective Peroxisome Proliferator-Activated Receptor δ (PPARδ) Agonist. The product has currently been launched in the United States,European Unionand approved in the UK, for use in combination with ursodeoxycholic acid to treat patients who respond inadequately or are intolerant to ursodeoxycholic acidPrimary Biliary CholangitisPatient.

The RESPONSE study is a randomized, placebo-controlled, international multicenter Phase 3 trial investigating the efficacy and safety of Seladelpar in PBC patients. Meanwhile, the long-term safety and tolerability of Seladelpar are being evaluated in an open-label trial called the ASSURE study. At this year's APASL, the 12-month trial results of Asian patients from the RESPONSE and ASSURE studies were reported.

RESPONSE StudyInclude PBC patients who respond poorly to or are intolerant of ursodeoxycholic acid (UDCA).Patients with alkaline phosphatase (ALP) ≥1.67 times the upper limit of normal (ULN) and total bilirubin (TB) ≤2 times ULN. Patients take 10mg Seladelpar or placebo orally daily (randomized 2:1), for 12 months. Stratification is based on ALP and the Numerical Rating Scale (NRS; 0-10) for pruritus. The primary endpoint is a composite response at month 12 (defined as ALP <1.67 times ULN, ALP reduction ≥15%, and TB ≤ULN). Key secondary endpoints are ALP normalization at month 12 and changes in NRS at month 6.ASSURE Studyinclusion of PBC patients previously involved in Seladelpar studies, with a 5-year follow-up to assess the long-term safety and efficacy of Seladelpar, and the primary endpoint was adverse events during treatment and biochemical and hematologic results.

Among the 193 PBC patients in the RESPONSE study, 11 were Asian patients (7 received Seladelpar treatment and 4 received placebo), and the remaining 182 were non-Asian patients. At the 12th month of treatment,Composite response rate of Seladelpar treatment in Asian patients is 100%(7/7), the composite response rate in the placebo group was 0% (0/4); among non-Asian patients, the composite response rate for those treated with Seladelpar was 59.5% (72/121), and 21.3% (13/61) in the placebo group. Among the 174 PBC patients in the ASSURE study, 13 were Asian and the remaining 161 were non-Asian. Follow-up data at the 12th month were available for 8 Asian patients and 140 non-Asian patients, showing thatThe composite response rates for Asian and non-Asian patients treated with Seladelpar 10mg were 75% (6/8) and 70% (98/140), respectively.。

In terms of ALP normalization, in the RESPONSE study at the 12th month, 71.4% (5/7) of Asian patients treated with Seladelpar achieved ALP normalization, while 22.3% (27/121) of non-Asian patients achieved ALP normalization, and no patients in the placebo group achieved ALP normalization. In the ASSURE study at the 12th month, the ALP normalization rate for Asian patients treated with Seladelpar was 25% (2/8), and for non-Asian patients, it was 37.9% (53/140). All patients receiving Seladelpar, whether Asian or non-Asian, experienced a similar degree of reduction in ALP levels. The incidence of adverse events in Asian patients treated with Seladelpar was similar to those treated with placebo, and no serious adverse events occurred.

The RESPONSE and ASSURE studies both showed that Seladelpar effectively reduced cholestasis-related biomarkers in Asian or non-Asian PBC patients, with good safety and tolerability.

Sofosbuvir/Velpatasvir Combined with Preventive Use of TAF Shows High Safety and Efficacy in HBV/HCV Co-infected Patients

This conference also showcased a prospective, single-arm, open-label, 12-week clinical study with a subsequent 12/48-week observational period from 16 centers in China. The study included a total of 105 cases.Hepatitis B Virus (HBV)/Hepatitis C Virus (HCV) GT1-6 CoinfectionAdult patients were enrolled in the study. Among them, 83 non-cirrhotic patients were assigned to Group 1, and 22 patients with compensated cirrhosis were assigned to Group 2. All patients received treatment for HBV and HCV. The specific treatment regimen was as follows: 4 weeks of tenofovir alafenamide (TAF) monotherapy, followed by 12 weeks of combination therapy with TAF and sofosbuvir/velpatasvir (SOF/VEL). Non-cirrhotic patients continued with once-daily TAF monotherapy for an additional 12 weeks, while patients with compensated cirrhosis continued with once-daily TAF monotherapy for 48 weeks.

The study results showed that at the end of SOF/VEL treatment,The sustained virological response rate (SVR) was 97.6%., among which,The SVR rate in Group 2 reached 100%.. The HCV RNA and HBV DNA levels of all patients significantly decreased (p<0.001). Compared with before treatment, at week 12 of treatment in Group 1, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) significantly decreased (p<0.05), while the albumin (ALB) level significantly increased (p<0.001). At week 48 of treatment in Group 2, the ALT and AST levels significantly decreased (p<0.001), while the ALB and platelet (PLT) levels significantly increased (p<0.05). The liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI), and FIB-4 index (FIB-4) all significantly decreased (p<0.05). Only one patient with GT3 in Group 1 experienced HBV reactivation. No drug-related adverse events were observed in this study.

The study results indicate that SOF/VEL can significantly reduce HCV RNA levels in patients with HBV/HCV co-infection, improve liver function, and has a high safety profile. After antiviral treatment, liver function indicators in patients with compensated cirrhosis improved significantly. Additionally, the preventive use of TAF in HBV/HCV co-infected patients can, to a certain extent, prevent HBV reactivation.。

References:

[1] Gilead Sciences Press Release.