SOVALDI Film-coated tablet Ref.[7098] Active ingredients: Sofosbuvir

Pharmacotherapeutic group: Antivirals for systemic use, direct-acting antiviral
ATC code: J05AP08

Mechanism of action

Sofosbuvir is a pan-genotypic inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into HCV RNA by the NS5B polymerase and acts as a chain terminator. In a biochemical assay, GS-461203 inhibited the polymerase activity of the recombinant NS5B from HCV genotype 1b, 2a, 3a and 4a with a 50% inhibitory concentration (IC₅₀) value ranging from 0.7 to 2.6 μM. GS-461203 (the active metabolite of sofosbuvir) is not an inhibitor of human DNA and RNA polymerases nor an inhibitor of mitochondrial RNA polymerase.

Antiviral activity

In HCV replicon assays, the effective concentration (EC₅₀) values of sofosbuvir against full-length replicons from genotype 1a, 1b, 2a, 3a and 4a were 0.04, 0.11, 0.05, 0.05 and 0.04 μM, respectively, and EC₅₀ values of sofosbuvir against chimeric 1b replicons encoding NS5B from genotype 2b, 5a or 6a were 0.014 to 0.015 μM. The mean ± SD EC₅₀ of sofosbuvir against chimeric replicons encoding NS5B sequences from clinical isolates was 0.068 ± 0.024 μM for genotype 1a (n=67), 0.11 ± 0.029 μM for genotype 1b (n=29), 0.035 ± 0.018 μM for genotype 2 (n=15) and 0.085 ± 0.034 μM for genotype 3a (n=106). In these assays, the in vitro antiviral activity of sofosbuvir against the less common genotypes 4, 5 and 6 was similar to that observed for genotypes 1, 2 and 3.

The presence of 40% human serum had no effect on the anti-HCV activity of sofosbuvir.

Resistance

In cell culture

HCV replicons with reduced susceptibility to sofosbuvir have been selected in cell culture for multiple genotypes including 1b, 2a, 2b, 3a, 4a, 5a and 6a. Reduced susceptibility to sofosbuvir was associated with the primary NS5B substitution S282T in all replicon genotypes examined. Site-directed mutagenesis of the S282T substitution in replicons of 8 genotypes conferred 2- to 18-fold reduced susceptibility to sofosbuvir and reduced the replication viral capacity by 89% to 99% compared to the corresponding wild-type. In biochemical assays, recombinant NS5B polymerase from genotypes 1b, 2a, 3a and 4a expressing the S282T substitution showed reduced susceptibility to GS-461203 compared to respective wild-types.

In clinical studies – Adults

In a pooled analysis of 991 patients who received sofosbuvir in Phase 3 studies, 226 patients qualified for resistance analysis due to virologic failure or early study drug discontinuation and having HCV RNA >1,000 IU/mL. Post-baseline NS5B sequences were available for 225 of the 226 patients, with deep sequencing data (assay cutoff of 1%) from 221 of these patients. The sofosbuvir-associated resistance substitution S282T was not detected in any of these patients by deep sequencing or population sequencing. The S282T substitution in NS5B was detected in a single subject receiving Sovaldi monotherapy in a Phase 2 study. This subject harboured <1% HCV S282T at baseline and developed S282T (>99%) at 4 weeks post-treatment which resulted in a 13.5-fold change in sofosbuvir EC₅₀ and reduced viral replication capacity. The S282T substitution reverted to wild-type over the next 8 weeks and was no longer detectable by deep sequencing at 12 weeks post-treatment.

Two NS5B substitutions, L159F and V321A, were detected in post-treatment relapse samples from multiple genotype 3 HCV infected patients in the Phase 3 clinical studies. No shift in the phenotypic susceptibility to sofosbuvir or ribavirin of subject isolates with these substitutions was detected. In addition, S282R and L320F substitutions were detected on treatment by deep sequencing in a pre-transplant subject with a partial treatment response. The clinical significance of these findings is unknown.

Effect of baseline HCV polymorphisms on treatment outcome

Adult population

Baseline NS5B sequences were obtained for 1,292 patients from Phase 3 studies by population sequencing and the S282T substitution was not detected in any subject with available baseline sequence. In an analysis evaluating the effect of baseline polymorphisms on treatment outcome, no statistically significant association was observed between the presence of any HCV NS5B variant at baseline and treatment outcome.

Paediatric population

The presence of NS5B RAVs did not impact treatment outcome; all patients with baseline NS5B nucleoside inhibitor RAVs achieved SVR following treatment with sofosbuvir.

Cross-resistance

HCV replicons expressing the sofosbuvir-associated resistance substitution S282T were fully susceptible to other classes of anti-HCV agents. Sofosbuvir retained activity against the NS5B substitutions L159F and L320F associated with resistance to other nucleoside inhibitors. Sofosbuvir was fully active against substitutions associated with resistance to other direct-acting antivirals with different mechanisms of actions, such as NS5B non-nucleoside inhibitors, NS3 protease inhibitors and NS5A inhibitors.

Clinical efficacy and safety

The efficacy of sofosbuvir was evaluated in five Phase 3 studies in a total of 1,568 adult patients with genotypes 1 to 6 chronic hepatitis C. One study was conducted in treatment-naïve patients with genotype 1, 4, 5 or 6 chronic hepatitis C in combination with peginterferon alfa 2a and ribavirin and the other four studies were conducted in patients with genotype 2 or 3 chronic hepatitis C in combination with ribavirin including one in treatment-naïve patients, one in interferon intolerant, ineligible or unwilling patients, one in patients previously treated with an interferon-based regimen, and one in all patients irrespective of prior treatment history or ability to receive treatment with interferon. Patients in these studies had compensated liver disease including cirrhosis. Sofosbuvir was administered at a dose of 400 mg once daily. The ribavirin dose was weight-based at 1,000-1,200 mg daily administered in two divided doses, and the peginterferon alfa 2a dose, where applicable, was 180 μg per week. Treatment duration was fixed in each study and was not guided by patients' HCV RNA levels (no response guided algorithm).

Plasma HCV RNA values were measured during the clinical studies using the COBAS TaqMan HCV test (version 2.0), for use with the High Pure System. The assay had a lower limit of quantification (LLOQ) of 25 IU/mL. Sustained virologic response (SVR) was the primary endpoint to determine the HCV cure rate for all studies which was defined as HCV RNA less than LLOQ at 12 weeks after the end of treatment (SVR12).

Clinical studies in patients with genotype 1, 4, 5 and 6 chronic hepatitis C

Treatment-naïve adult patients – NEUTRINO (study 110)

NEUTRINO was an open-label, single-arm study that evaluated 12 weeks of treatment with sofosbuvir in combination with peginterferon alfa 2a and ribavirin in treatment-naïve patients with genotype 1, 4, 5 or 6 HCV infection.

Treated patients (n=327) had a median age of 54 years (range: 19 to 70); 64% of the patients were male; 79% were White; 17% were Black; 14% were Hispanic or Latino; mean body mass index was 29 kg/m² (range: 18 to 56 kg/m²); 78% had baseline HCV RNA greater than 6 log₁₀ IU/mL; 17% had cirrhosis; 89% had HCV genotype 1 and 11% had HCV genotype 4, 5 or 6. Table 7 presents the response rates for the treatment group of sofosbuvir + peginterferon alfa + ribavirin.

Table 7. Response rates in study NEUTRINO:

^a The denominator for relapse is the number of patients with HCV RNA <LLOQ at their last on-treatment assessment.
^b Other includes patients who did not achieve SVR12 and did not meet virologic failure criteria (e.g. lost to follow-up).

Response rates for selected subgroups are presented in Table 8.

Table 8. SVR12 rates for selected subgroups in NEUTRINO:

SVR12 rates were similarly high in patients with baseline IL28B C/C allele [94/95 (99%)] and non-C/C (C/T or T/T) allele [202/232 (87%)].

27/28 patients with genotype 4 HCV achieved SVR12. A single subject with genotype 5 and all 6 patients with genotype 6 HCV infection in this study achieved SVR12.

Clinical studies in patients with genotype 2 and 3 chronic hepatitis C

Treatment-naïve adults – FISSION (study 1231)

FISSION was a randomised, open-label, active-controlled study that evaluated 12 weeks of treatment with sofosbuvir and ribavirin compared to 24 weeks of treatment with peginterferon alfa 2a and ribavirin in treatment-naïve patients with genotype 2 or 3 HCV infection. The ribavirin doses used in the sofosbuvir + ribavirin and peginterferon alfa 2a + ribavirin arms were weight-based 1,000-1,200 mg/day and 800 mg/day regardless of weight, respectively. Patients were randomised in a 1:1 ratio and stratified by cirrhosis (presence versus absence), HCV genotype (2 versus 3) and baseline HCV RNA level (<6 log₁₀ IU/mL versus ≥6 log₁₀ IU/mL). Patients with genotype 2 or 3 HCV were enrolled in an approximately 1:3 ratio.

Treated patients (n=499) had a median age of 50 years (range: 19 to 77); 66% of the patients were male; 87% were White; 3% were Black; 14% were Hispanic or Latino; mean body mass index was 28 kg/m² (range: 17 to 52 kg/m²); 57% had baseline HCV RNA levels greater than 6 log₁₀ IU/mL; 20% had cirrhosis; 72% had HCV genotype 3. Table 9 presents the response rates for the treatment groups of sofosbuvir + ribavirin and peginterferon alfa + ribavirin.

Table 9. Response rates in study FISSION:

^a The efficacy analysis includes 3 patients with recombinant genotype 2/1 HCV infection.
^b The denominator for relapse is the number of patients with HCV RNA <LLOQ at their last on-treatment assessment.
^c Other includes patients who did not achieve SVR12 and did not meet virologic failure criteria (e.g. lost to follow-up).

The difference in the overall SVR12 rates between sofosbuvir + ribavirin and peginterferon alfa + ribavirin treatment groups was 0.3% (95% confidence interval: -7.5% to 8.0%) and the study met the predefined non-inferiority criterion.

Response rates for patients with cirrhosis at baseline are presented in Table 10 by HCV genotype.

Table 10. SVR12 rates by cirrhosis and genotype in study FISSION:

^a The efficacy analysis includes 3 patients with recombinant genotype 2/1 HCV infection.

Interferon intolerant, ineligible or unwilling adults – POSITRON (study 107)

POSITRON was a randomised, double-blinded, placebo-controlled study that evaluated 12 weeks of treatment with sofosbuvir and ribavirin (n=207) compared to placebo (n=71) in patients who are interferon intolerant, ineligible or unwilling. Patients were randomised in 3:1 ratio and stratified by cirrhosis (presence versus absence).

Treated patients (n=278) had a median age of 54 years (range: 21 to 75); 54% of the patients were male; 91% were White; 5% were Black; 11% were Hispanic or Latino; mean body mass index was 28 kg/m² (range: 18 to 53 kg/m²); 70% had baseline HCV RNA levels greater than 6 log₁₀ IU/mL; 16% had cirrhosis; 49% had HCV genotype 3. The proportions of patients who were interferon intolerant, ineligible, or unwilling were 9%, 44%, and 47%, respectively. Most patients had no prior HCV treatment (81.3%). Table 11 presents the response rates for the treatment groups of sofosbuvir + ribavirin and placebo.

Table 11. Response rates in study POSITRON:

^a The denominator for relapse is the number of patients with HCV RNA <LLOQ at their last on-treatment assessment.
^b Other includes patients who did not achieve SVR12 and did not meet virologic failure criteria (e.g. lost to follow-up).

The SVR12 rate in the sofosbuvir + ribavirin treatment group was statistically significant when compared to placebo (p<0.001).

Table 12 presents the subgroup analysis by genotype for cirrhosis and interferon classification.

Table 12. SVR12 rates for selected subgroups by genotype in POSITRON:

Previously treated adults – FUSION (study 108)

FUSION was a randomised, double-blinded study that evaluated 12 or 16 weeks of treatment with sofosbuvir and ribavirin in patients who did not achieve SVR with prior interferon-based treatment (relapsers and nonresponders). Patients were randomised in a 1:1 ratio and stratified by cirrhosis (presence versus absence) and HCV genotype (2 versus 3).

Treated patients (n=201) had a median age of 56 years (range: 24 to 70); 70% of the patients were male; 87% were White; 3% were Black; 9% were Hispanic or Latino; mean body mass index was 29 kg/m² (range: 19 to 44 kg/m²); 73% had baseline HCV RNA levels greater than 6 log₁₀ IU/mL; 34% had cirrhosis; 63% had HCV genotype 3; 75% were prior relapsers. Table 13 presents the response rates for the treatment groups of sofosbuvir + ribavirin for 12 weeks and 16 weeks.

Table 13. Response rates in study FUSION:

Table 14 presents the subgroup analysis by genotype for cirrhosis and response to prior HCV treatment.

Table 14. SVR12 rates for selected subgroups by genotype in study FUSION:

Treatment-naïve and previously treated adults – VALENCE (study 133)

VALENCE was a Phase 3 study that evaluated sofosbuvir in combination with weight-based ribavirin for the treatment of genotype 2 or 3 HCV infection in treatment-naïve patients or patients who did not achieve SVR with prior interferon-based treatment, including patients with compensated cirrhosis. The study was designed as a direct comparison of sofosbuvir and ribavirin versus placebo for 12 weeks. However, based on emerging data, the study was unblinded and all HCV genotype 2 patients continued to receive sofosbuvir and ribavirin for 12 weeks, whilst treatment for HCV genotype 3 patients was extended to 24 weeks. Eleven HCV genotype 3 patients had already completed treatment with sofosbuvir and ribavirin for 12 weeks at the time of the amendment.

Treated patients (n=419) had a median age of 51 years (range: 19 to 74); 60% of the patients were male; median body mass index was 25 kg/m² (range: 17 to 44 kg/m²); the mean baseline HCV RNA level was 6.4 log₁₀ IU/mL; 21% had cirrhosis; 78% had HCV genotype 3; 65% were prior relapsers. Table 15 presents the response rates for the treatment groups of sofosbuvir + ribavirin for 12 weeks and 24 weeks.

Placebo recipients are not included in the tables since none achieved SVR12.

Table 15. Response rates in study VALENCE:

^a The denominator for relapse is the number of patients with HCV RNA <LLOQ at their last on-treatment assessment.
^b Other includes patients who did not achieve SVR12 and did not meet virologic failure criteria (e.g. lost to follow-up).

Table 16 presents the subgroup analysis by genotype for cirrhosis and exposure to prior HCV treatment.

Table 16. SVR12 rates for selected subgroups by genotype in study VALENCE:

SVR12 to SVR24 concordance

The concordance between SVR12 and SVR24 (SVR 24 weeks after the end of the treatment) following treatment with sofosbuvir in combination with ribavirin or ribavirin and pegylated interferon demonstrates a positive predictive value of 99% and a negative predictive value of 99%.

Clinical efficacy and safety in special populations

HCV/HIV co-infected adult patients – PHOTON-1 (study 123)

Sofosbuvir was studied in an open-label clinical study evaluating the safety and efficacy of 12 or 24 weeks of treatment with sofosbuvir and ribavirin in patients with genotype 1, 2 or 3 chronic hepatitis C co-infected with HIV-1. Genotype 2 and 3 patients were either treatment-naïve or experienced, whereas genotype 1 patients were naïve to prior treatment. Treatment duration was 12 weeks in treatment-naïve patients with genotype 2 or 3 HCV infection, and 24 weeks in treatment-experienced patients with genotype 3 HCV infection, as well as patients with genotype 1 HCV infection. Patients received 400 mg sofosbuvir and weight-based ribavirin (1,000 mg for patients weighing <75 kg or 1,200 mg for patients weighing ≥75 kg). Patients were either not on antiretroviral therapy with a CD4+ cell count >500 cells/mm³ or had virologically suppressed HIV-1 with a CD4+ cell count >200 cells/mm³. 95% of patients received antiretroviral therapy at the time of enrolment. Preliminary SVR12 data are available for 210 patients. Table 17 presents the response rates by genotype and exposure to prior HCV treatment.

Table 17. Response rates in study PHOTON-1:

^a The denominator for relapse is the number of patients with HCV RNA <LLOQ at their last on-treatment assessment.
^b Other includes patients who did not achieve SVR12 and did not meet virologic failure criteria (e.g. lost to follow-up).

Table 18 presents the subgroup analysis by genotype for cirrhosis.

Table 18. SVR12 rates for selected subgroups by genotype in study PHOTON-1:

TN = treatment-naïve; TE = treatment-experienced.

Adult patients awaiting liver transplantation – Study 2025

Sofosbuvir was studied in HCV infected patients prior to undergoing liver transplantation in an open-label clinical study evaluating the safety and efficacy of sofosbuvir and ribavirin administered pre-transplant to prevent post-transplant HCV reinfection. The primary endpoint of the study was post-transplant virologic response (pTVR, HCV RNA <LLOQ at 12 weeks post-transplant). HCV infected patients, regardless of genotype, with hepatocellular carcinoma (HCC) meeting the MILAN criteria received 400 mg sofosbuvir and 1,000-1,200 mg ribavirin daily for a maximum of 24 weeks, subsequently amended to 48 weeks, or until the time of liver transplantation, whichever occurred first. An interim analysis was conducted on 61 patients who received sofosbuvir and ribavirin; the majority of patients had HCV genotype 1, 44 patients were CPT class A and 17 patients were CPT class B. Of these 61 patients, 44 patients underwent liver transplantation following up to 48 weeks of treatment with sofosbuvir and ribavirin; 41 had HCV RNA <LLOQ at the time of transplantation. The virologic response rates of the 41 patients transplanted with HCV RNA <LLOQ is described in Table 19. Duration of viral suppression prior to transplantation was the most predictive factor for pTVR in those who were HCV RNA <LLOQ at the time of transplantation.

Table 19. Virologic response post-transplant in patients with HCV RNA <LLOQ at the time of liver transplantation:

^a Evaluable patients are defined as those who have reached the specified time point at the time of the interim analysis.
^b pTVR: post-transplant virologic response (HCV RNA <LLOQ at 12 weeks post-procedure).

In patients that discontinued therapy at 24 weeks, according to protocol, the relapse rate was 11/15.

Adult liver transplant recipients – Study 0126

Sofosbuvir was studied in an open-label clinical study evaluating the safety and efficacy of 24 weeks of treatment with sofosbuvir and ribavirin in liver transplant recipients with chronic hepatitis C. Eligible patients were ≥18 years old and had undergone liver transplantation 6 to 150 months prior to screening. Patients had HCV RNA ≥10⁴ IU/mL at screening and documented evidence of chronic HCV infection pre-transplantation. The starting dose of ribavirin was 400 mg given in a divided daily dose. If patients maintained haemoglobin levels ≥12 g/dL, ribavirin dose was increased at weeks 2, 4, and up to every 4 weeks until the appropriate weight-based dose was reached (1,000 mg daily in patients <75 kg, 1,200 mg daily in patients ≥75 kg). The median ribavirin dose was 600 mg-800 mg daily at weeks 4-24.

Forty patients (33 with HCV genotype 1 infection, 6 with HCV genotype 3 infection, and 1 with HCV genotype 4 infection) were enrolled, 35 of whom had previously failed interferon-based treatment, and 16 of whom had cirrhosis. 28 out of 40 (70%) patients achieved SVR12: 22/33 (73%) with HCV genotype 1 infection, 6/6 (100%) with HCV genotype 3 infection, and 0/1 (0%) with HCV genotype 4 infection. All patients who achieved SVR12 achieved SVR24 and SVR48.

Overview of outcomes by therapeutic regimen and treatment duration, a comparison across studies

The following tables (Table 20 to Table 23) present data from Phase 2 and Phase 3 studies relevant to the dosing to help clinicians determine the best regimen for individual patients.

Table 20. Outcomes by therapeutic regimen and treatment duration, a comparison across studies in genotype 1 HCV infection:

n = number of patients with SVR12 response; N = total number of patients per group.
^a For previously treated patients with genotype 1 HCV infection, no data exists with the combination of sofosbuvir, peginterferon alfa and ribavirin. Consideration should be given to treating these patients, and potentially extending the duration of therapy with sofosbuvir, peginterferon alfa and ribavirin beyond 12 weeks and up to 24 weeks; especially for those subgroups who have one or more factors historically associated with lower response rates to interferon-based therapies (prior null response to peginterferon alfa and ribavirin therapy, advanced fibrosis/cirrhosis, high baseline viral concentrations, black race, IL28B non CC genotype).
^b These are exploratory or Phase 2 studies. The outcomes should be interpreted with caution, as subject numbers are small and SVR rates may be impacted by the selection of patients.
^c Summary data from both studies.

Table 21. Outcomes by therapeutic regimen and treatment duration, a comparison across studies in genotype 2 HCV infection:

n = number of patients with SVR12 response; N = total number of patients per group.
^a These data are preliminary.
^b These are exploratory or Phase 2 studies. The outcomes should be interpreted with caution, as subject numbers are small and SVR rates may be impacted by the selection of patients. In the ELECTRON study (N=11), the duration of peginterferon alfa ranged from 4-12 weeks in combination with sofosbuvir + ribavirin.
^c All patients were non-cirrhotic in these two studies.

Table 22. Outcomes by therapeutic regimen and treatment duration, a comparison across studies in genotype 3 HCV infection:

n = number of patients with SVR12 response; N = total number of patients per group.
^a These data are preliminary.
^b These are exploratory or Phase 2 studies. The outcomes should be interpreted with caution, as subject numbers are small and SVR rates may be impacted by the selection of patients. In the ELECTRON study (N=11), the duration of peginterferon alfa ranged from 4-12 weeks in combination with sofosbuvir + ribavirin.
^c All patients were non-cirrhotic in these two studies.

Table 23. Outcomes by therapeutic regimen and treatment duration, a comparison across studies in genotype 4, 5 and 6 HCV infection:

Patients with renal impairment

Study 0154 was an open-label clinical study that evaluated the safety and efficacy of 24 weeks of treatment with sofosbuvir in combination with ribavirin in 20 genotype 1 or 3 HCV-infected patients with severe renal impairment not requiring dialysis. Following treatment with sofosbuvir 200 mg or 400 mg in combination with ribavirin the SVR12 rate in patients with ESRD was 40% and 60%, respectively. The safety and efficacy of 12 weeks of treatment with ledipasvir/sofosbuvir in 18 genotype 1 HCV-infected patients with severe renal impairment not requiring dialysis was also studied in Study 0154. At baseline, two patients had cirrhosis and the mean eGFR was 24.9 mL/min (range: 9.0-39.6). SVR12 was achieved in 100 % (18/18) of patients treated with ledipasvir/sofosbuvir.

Study 4063 was an open-label study that evaluated a fixed dose combination of sofosbuvir and ledipasvir in 95 patients with HCV-infection and ESRD requiring dialysis. The SVR rates for the 8, 12, and 24 week ledipasvir/sofosbuvir treatment groups were 93% (42/45), 100% (31/31), and 79% (15/19), respectively. Of the seven patients who did not achieve SVR12, none experienced virologic failure or relapsed.

Study 4062 was an open-label study that evaluated a fixed dose combination of sofosbuvir and velpatasvir in 59 HCV-infected patients with ESRD requiring dialysis. The SVR rate was 95% (56/59); of the three patients that did not achieve SVR12, one had completed sofosbuvir with velpatasvir treatment and relapsed.

Paediatric population

The efficacy of sofosbuvir in HCV-infected patients aged 3 years and above was evaluated in a Phase 2, open label clinical trial that enrolled 106 patients with genotype 2 (n=31) or genotype 3 (n=75) chronic HCV infection. Patients with HCV genotype 2 or 3 infection in the trial were treated with sofosbuvir with ribavirin for 12 or 24 weeks, respectively.

Patients aged 12 to <18 Years

Sofosbuvir was evaluated in 52 patients 12 to <18 years with genotype 2 (n=13) or genotype 3 (n=39) HCV infection. The median age was 15 years (range: 12 to 17); 40% of the patients were female; 90% were White, 4% were Black, and 2% were Asian; 4% were Hispanic/Latino; mean weight was 60.4 kg (range: 29.6 to 75.6 kg); 17% were treatment experienced; 65% had baseline HCV RNA levels greater than or equal to 800,000 IU/mL; and no patients had known cirrhosis. The majority of patients (69%) had been infected through vertical transmission.

The SVR12 rate was 98% overall (100% [13/13] in genotype 2 patients and 97% [38/39]) in genotype 3 patients. No patient experienced on-treatment virologic failure or relapse; one patient with genotype 3 HCV infection achieved SVR4 but did not return for the SVR12 visit.

Patients aged 6 to <12 Years

Sofosbuvir was evaluated in 41 patients 6 to <12 years of age with genotype 2 (n=13), or genotype 3 (n=28) HCV infection. The median age was 9 years (range: 6 to 11); 73% of the patients were female; 71% were White and 20% were Asian; 15% were Hispanic/Latino; mean weight was 33.7 kg (range: 15.1 to 80.0 kg); 98% were treatment naive; 46% had baseline HCV RNA levels greater than or equal to 800,000 IU/mL; and no patients had known cirrhosis. The majority of patients (98%) had been infected through vertical transmission.

The SVR12 rate was 100% (100% [13/13] in genotype 2 patients and 100% [28/28] in genotype 3 patients). No patients experienced on-treatment virologic failure or relapse.

Patients aged 3 to <6 Years

Sofosbuvir was evaluated in 13 patients 3 to <6 years with genotype 2 (n=5) or genotype 3 (n=8) HCV infection. The median age was 4 years (range: 3 to 5); 77% of the patients were female; 69% were White, 8% were Black, and 8% were Asian; 8% were Hispanic/Latino; mean weight was 16.8 kg (range: 13.0 to 19.2 kg); 100% were treatment naive; 23% had baseline HCV RNA levels greater than or equal to 800,000 IU/mL; and no patients had known cirrhosis. The majority of patients (85%) had been infected through vertical transmission.

The SVR12 rate was 92% overall (80% [4/5] in genotype 2 patients and 100% [8/8] in genotype 3 patients). No patients experienced on-treatment virologic failure or relapse; one patient with genotype 2 HCV prematurely discontinued study treatment after three days due to abnormal taste of the medication and did not return for post-treatment Week 12.