Sofosbuvir - Velpatasvir FDC for HCV Genotypes 1 to 6 Infection – Integrated Analyses of ASTRAL Studies

Table of Content

Sofosbuvir-velpatasvir FDC (SOF-VEL) is the first all-oral pan-genotypic single tablet regimen approved for chronic hepatitis C virus (HCV). Four international Phase 3 clinical studies (ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-4) evaluated the once-daily, FDC of the nucleotide analog polymerase inhibitor sofosbuvir (SOF) with velpatasvir (VEL), an pangenotypic NS5A inhibitor, for the treatment of genotype 1-6 chronic HCV infection. The following infographic on the ASTRAL studies provides an overall pooled result on the efficacy and safety of SOF-VEL in chronic HCV.

Introduction

A clinician has to take into account patients’ treatment history, HCV genotype and in some cases patterns of antiviral resistance before initiating the treatment of patients infected with HCV. The present analysis is a combination of results of 3 phase III trials conducted to evaluate the efficacy and safety of the recently introduced pangenotypic sofosbuvir-velpatasvir fixed-dose combination (FDC) across the HCV genotypes 1, 2, 3, 4, 5, and 6.

Aim

To evaluate the efficacy and safety of an FDC of 100 mg velpatasvir and 400 mg sofosbuvir in treatment-naïve as well as treatment-experienced patients chronically infected with HCV genotypes 1, 2, 3, 4, 5 or 6, including those with cirrhosis.

Method

Study Design

  • Phase III open-label, randomized, multicenter studies
  • N=1035
  • Patients received a FDC tablet of 100 mg velpatasvir and 400 mg sofosbuvir orally once daily for 12 weeks

RBV=Ribavirin, SVR=Sustained virologic response 12 week after treatment end

Patient inclusion

  • Patients aged >18 years with chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection
  • Treatment naïve patients with no previous exposure to interferon (IFN) formulation, ribavirin, or any HCV direct acting antiviral agent
  • Upto 20% treatment-experienced patients who had received IFN therapy but did not achieve sustained virologic response (SVR 12) after completion of the treatment
  • Upto 20% patients with compensated cirrhosis

Exclusion criteria

  • Patients with a history of decompensation or hepatocellular carcinoma

Endpoints

Primary endpoints

  • Sustained virologic response, defined as HCV RNA level of less than 15 IU/ml at 12 weeks after the end of treatment

Secondary endpoints

  • Rate of adverse events
  • Treatment discontinuations due to adverse events

Results

  • Majority had baseline HCV RNA>8,00,000 IU/ml
  • Overall, 98% achieved SVR 12 as shown in Figure 1.
Figure 1. Overall % of patients who achieved SVR 12

  • Integrated efficacy analysis from ASTRAL 1, ASTRAL 2 and ASTRAL 3 studies are shown in Figure 2
Figure 2. Integrated efficacy analysis from ASTRAL 1, 2 and 3 studies

  • Treatment with sofosbuvir-velpatasvir for 12 weeks was well tolerated with a safety profile similar to placebo
  • Presence of cirrhosis, advanced age and mild renal impairment did not adversely affect the safety outcome
  • None of the patients had on-treatment virological failure
  • The most common side effects were headache, fatigue, nausea, insomnia and nasopharyngitis
  • Serious adverse events were reported in 2% of the patients.
  • Treatment was discontinued in only 2 patients out of 1035 due to adverse events

Conclusion

  • The FDC regimen of velpatasvir and sofosbuvir for 12 weeks was found to be highly effective in patients infected with HCV genotypes 1, 2, 3, 4, 5 or 6
  • The SVR12 remained unaffected in previously treated as well as untreated patients including those with uncompensated cirrhosis
    • The regimen was safe and well tolerated by the patients

References

  1. N Engl J Med. 2015; 373(27): 2599-607.
  2. N Engl J Med. 2015; 373(27): 2608-17.
  3. Gastroenterology 2016; 150(4), Supplement 1:S1093.
  4. Gastroenterology 2016; 150(4), Supplement 1:S1092.