Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection

Princess Igwe, Mercer University College of Pharmacy

Hepatitis C virus (HCV) genotypes 2 and 3 account for about 35% of global HCV infections and is reported to most commonly affect persons in low-income regions in Asia, sub-Saharan Africa, Latin America, and Eastern Europe.1

It is suggested that although genotypes 2 and 3 are treated similarly, HCV genotype 3 may be associated with more rapid disease progression and lower rates of response to treatment, especially in patients with cirrhosis and patients who have had no response to previous treatment.2

Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection3
Design Two randomized, phase 3, open-label studies; N = 818
Objective To compare treatment with a fixed-dose combination tablet of sofosbuvir and velpatasvir for 12 weeks with standard treatment with sofosbuvir plus ribavirin for 12 or 24 weeks in patients who had received prior treatment for hepatitis C virus (HCV) genotype 2 or 3 infection and in those who had not received such treatment, including those with compensated cirrhosis
Study Groups
  • Fixed-dose combination tablet containing 400 mg of sofosbuvir and 100 mg of velpatasvir once daily for 12 weeks  (HCV Genotype 2, n = 134; HCV Genotype 3, n = 277)
  • 400 mg of sofosbuvir plus ribavirin for 12 weeks (for patients with HCV genotype 2, n = 132) or 24 weeks (for patients with HCV genotype 3, n = 275)
Methods In one trial, patients with HCV genotype 2 were assigned in a 1:1 ratio to receive sofosbuvir–velpatasvir, in a once-daily, fixed-dose combination tablet, or sofosbuvir plus weight-based ribavirin for 12 weeks. In a second trial, patients with HCV genotype 3 were assigned in a 1:1 ratio to receive sofosbuvir–velpatasvir for 12 weeks or sofosbuvir–ribavirin for 24 weeks.
Duration 24 weeks
Primary Outcome Measure Sustained virologic response, defined as an HCV ribonucleic acid (RNA) level of less than 15 IU per milliliter at 12 weeks after the end of treatment
Baseline Characteristics Characteristic HCV Genotype 2 HCV Genotype 3
Sofosbuvir –Velpatasvir for 12 Wk Sofosbuvir– Ribavirin for 12 Wk Sofosbuvir–Velpatasvir for 12 Wk Sofosbuvir– Ribavirin for 24 Wk
Mean age (range) — yr 57 (26–81) 57 (23–76) 49 (21–76)

 

 

50 (19–74)
Male sex — no. (%) 86 (64) 72 (55) 170 (61) 174 (63)
Mean body-mass index (range) 28 (17–45) 29 (19–61) 26 (17–48) 27 (17–56)
Race — no. (%) – White 124 (93) 111 (84) 250 (90) 239 (87)
HCV RNA (Mean — log10 IU/ml) 6.5 ± 0.78 6.4 ± 0.74 6.2 ± 0.72 6.3 ± 0.71
Compensated cirrhosis — no. (%) 19 (14) 19 (14) 80 (29) 83 (30)
Previous HCV treatment — no. (%) No: 115 (86)

Yes: 19 (14)

No: 112 (85)

Yes: 20 (15)

No: 206 (74) No: 204 (74)

Yes: 71 (26)

Results Response HCV Genotype 2 HCV Genotype 3
Sofosbuvir–Velpatasvir for 12 Wk Sofosbuvir–Ribavirin for 12 Wk Sofosbuvir–Velpatasvir for 12 Wk Sofosbuvir–Ribavirin for 24 Wk
HCV RNA < 15 IU/ml during treatment period – no. (%)
At week two 76 (57) 79 (60) 171 (62) 137 (50)
At week four 120 (90) 119 (90) 253 (91) 240 (87)
HCV RNA < 15 IU/ml after end of treatment – no. (%)
At week four 133 (99) 127 (96) 268 (97) 225 (82)
At week 12* 133 (99) 124 (94) 264 (95) 221 (80)
95% CI at week 12 96–100 88–97 92–98 75–85
Virologic failure — no./total no. (%) On-treatment failure: 0

Relapse: 0

On-treatment failure: 0

Relapse: 6/132 (5)

On-treatment failure: 0

Relapse: 11/276 (4)

On-treatment failure: 1/275 (<1)

Relapse: 38/272 (14)

*Primary efficacy end point
Adverse Events Common Adverse Events:
HCV Genotype 2 HCV Genotype 3
Sofosbuvir–Velpatasvir for 12 Wk Sofosbuvir–Ribavirin for 12 Wk Sofosbuvir–Velpatasvir for 12 Wk Sofosbuvir–Ribavirin for 24 Wk
Fatigue 20 (15) 47 (36) 71 (26) 105 (38)
Headache 24 (18) 29 (22) 90 (32) 89 (32)
Nausea 14 (10) 19 (14) 46 (17) 58 (21)
Serious Adverse Events:
2 (1) 2 (2) 6 (2) 15 (5)
Percentage that Discontinued due to Adverse Events: Sofosbuvir–Velpatasvir for 12 Wk (HCV Genotype 2): n = 1 (1%); Sofosbuvir–Ribavirin for 24 Wk (HCV Genotype 3): n = 9 (3%)
Study Author Conclusions Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir–velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment with sofosbuvir–ribavirin.

The results of the two trials reported above show that treatment with sofosbuvir–velpatasvir for 12 weeks was very effective regardless of HCV genotype. The removal of ribavirin from the treatment regimen led to a shorter duration of treatment and fewer side effects in patients with HCV genotype 3 (including patients with cirrhosis and previous treatment failure), which represents an improvement over standard treatment with 24 weeks of sofosbuvir–ribavirin. However, the generalizability of the results of this study may be limited due to inclusion of a large number of Caucasian patients.

References

  1. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014;61:Suppl:S45-S57. doi: 10.1016/j.jhep.2014.07.027.
  2. Ampuero J, Romero-Gómez M, Reddy KR. Review article: HCV genotype 3 — the new treatment challenge. Aliment Pharmacol Ther 2014;39:686-698. doi: 10.1111/apt.12646.
  3. Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015. doi: 10.1056/NEJMoa1512612.

 

 

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