Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication SOVALDI is a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor indicated for the treatment of: Adult patients with genotype 1, 2, 3 or 4 chronic HCV infection without cirrhosis or with compensated cirrhosis as a component of a combination antiviral treatment regimen. FDA label
Also known as Sovaldi, GS-7977, PSI-7977
Sofosbuvir · 15 trials · 12 indications
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) 12 weeks following the last dose of study drug.
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
The percentage of participants permanently discontinuing any study drug due to an adverse event was summarized.
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks after cessation of therapy.
The number of participants experiencing adverse events leading to permanent discontinuation of study drug was summarized. Adverse events may or may not have been related to study treatment. Participants discontinuing study drug were permitted to remain on the study for further assessments.
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; \< 25 IU/mL) 12 weeks after study drug cessation.
Number of participants with grade 3 and 4 adverse events during treatment with and/or within 30 of completion of SOF/VEL/VOX in HCV infected
Intention to treat (ITT) analysis. Sustained Virologic Response as measure by an undetectable HCV RNA level 12 weeks after completion of therapy.
Measured by the portion of subjects with sustained virological response (undetectable HCV RNA)
Measured by the proportion of subjects who become HEV RNA negative (HEV RNA undetectable)
pTVR was defined as HCV RNA \< the lower limit of quantification (LLOQ, ie, 25 mL/IU) at Week 12 after transplant.
* Treatment-emergent deaths were those that occurred while taking study drug or to the minimum of 1) date of transplantation, 2) retreatment 1st dose date, or 3) last dose date + 30 days. * Only those participants who underwent liver transplantation were analyzed for death post-transplantation.
SVR12 was defined as HCV RNA \< LLOQ 12 weeks after the last dose of all study drugs.
SVR24 was defined as HCV RNA \< the limit of detection (LOD; \< 15 IU/mL) 24 weeks after the last dose of study drug.
Adverse events (AEs) occurring from baseline (Day 1 for all groups) to 30 days following the last dose of study drug were summarized across the participant population. A participant was counted once if they had a qualifying event.
Adverse events (AEs) occurring during the sofosbuvir treatment period and for 30 days following the last dose of sofosbuvir were summarized across the participant population. A participant was counted once if they had a qualifying event.
| Arm | Type | Description |
|---|---|---|
| Sofosbuvir+RBV 16 weeks | EXPERIMENTAL | Participants with HCV genotypes 1 and 3 will receive sofosbuvir plus ribavirin for 16 weeks. |
| Sofosbuvir+RBV 24 weeks | EXPERIMENTAL | Participants with HCV genotypes 1 and 3 will receive sofosbuvir plus ribavirin for 24 weeks. |
| Sofosbuvir+RBV+PEG 12 weeks | EXPERIMENTAL | Participants with genotype 1 or 6 will receive sofosbuvir+RBV+Peg-IFNα-2a for 12 weeks. |
| Sofosbuvir+RBV 12 weeks | EXPERIMENTAL | Participants with genotype 1, 2 or 6 will receive sofosbuvir+RBV for 12 weeks. |
| Genotype 2 treatment-naive | EXPERIMENTAL | Treatment-naive (TN) participants with HIV-1 and genotype 2 HCV coinfection will receive sofosbuvir plus RBV for 12 weeks. |
| Genotype 2/3 treatment-experienced | EXPERIMENTAL | Treatment-experienced (TE) participants with HIV-1 and genotype 2 or 3 HCV co-infection will receive sofosbuvir plus RBV for 24 weeks. |
| Genotype 1/3/4 treatment-naive | EXPERIMENTAL | Treatment naive (TN) participants with HIV-1 and genotype 1, 3, or 4 HCV co-infection will receive sofosbuvir plus RBV for 24 weeks. |
| Sofosbuvir+PEG+RBV | EXPERIMENTAL | - |
| Sofosbuvir+RBV | EXPERIMENTAL | Participants were randomized to receive sofosbuvir+RBV for 12 weeks. |
| PEG+RBV | ACTIVE_COMPARATOR | Participants were randomized to receive PEG+RBV for 24 weeks. |
| SOF/VEL/VOX | EXPERIMENTAL | Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks. |
| Sofosbuvir and Velpatasvir | EXPERIMENTAL | SOF/VEL FDC film-coated tablet, oral, SOF 400 mg/VEL 100 mg daily, 8 weeks |
| Sofosbuvir | EXPERIMENTAL | Sofosbuvir 400 MG film-coated tablet, oral administration of one tablet once daily for 24 weeks. |
| SOF+RBV | EXPERIMENTAL | Participants will receive sofosbuvir+RBV for 24 weeks. |
| SOF+RBV 12 Weeks | EXPERIMENTAL | Participants were randomized to receive sofosbuvir plus RBV plus placebo to match GS-0938 for 12 weeks. |
| SOF+RBV 24 Weeks | EXPERIMENTAL | Participants were randomized to receive sofosbuvir plus RBV plus placebo to match GS-0938 for 24 weeks. |
| GS-0938 Alone | EXPERIMENTAL | Participants were randomized to receive GS-0938 plus placebo to match sofosbuvir for up to 24 weeks. |
| GS-0938+SOF | EXPERIMENTAL | Participants were randomized to receive GS-0938 plus sofosbuvir for up to 24 weeks. |
| GS-0938+SOF+RBV | EXPERIMENTAL | Participants were randomized to receive GS-0938 plus sofosbuvir plus RBV for up to 24 weeks. |
| Placebo | EXPERIMENTAL | Deferred start group: Participants were randomized to receive placebo to match GS-0938 plus placebo to match sofosbuvir for 24 Weeks. |
| Retreatment Group - SOF+RBV 24 Weeks | EXPERIMENTAL | After discontinuing a regimen containing GS-0938, participants received sofosbuvir plus RBV for up to 24 weeks. |
| SOF+PEG+RBV 12 weeks | EXPERIMENTAL | Participants were randomized to receive sofosbuvir+PEG+RBV for 12 weeks. |
| SOF+PEG+RBV 24 weeks | EXPERIMENTAL | Participants were randomized to receive sofosbuvir+PEG+RBV for 24 weeks. |
| SOF+PEG+RBV 12 week/Rerandomization Group | EXPERIMENTAL | Participants were randomized to receive sofosbuvir+PEG+RBV for 12 weeks, then were rerandomized to receive sofosbuvir only or sofosbuvir+RBV for 12 additional weeks. |
| Sofosbuvir 200 mg (Genotype 1) | EXPERIMENTAL | Participants with genotype 1 HCV infection were randomized to receive sofosbuvir 200 mg (2 x 100 mg tablets)+placebo to match sofosbuvir (2 tablets)+PEG+RBV for 12 weeks followed by PEG+RBV for up to an additional 36 weeks. |
| Sofosbuvir 400 mg (Genotype 1) | EXPERIMENTAL | Participants with genotype 1 HCV infection were randomized to receive sofosbuvir 400 mg (4 x 100 mg tablets)+PEG+RBV for 12 weeks followed by PEG+RBV for up to an additional 36 weeks. |
| Placebo (Genotype 1) | ACTIVE_COMPARATOR | Participants with genotype 1 HCV infection were randomized to receive placebo to match sofosbuvir (4 tablets)+PEG+RBV for 12 weeks followed by PEG+RBV for up to an additional 36 weeks. |
| Sofosbuvir 400 mg (Genotype 2/3) | EXPERIMENTAL | Participants with genotype 2 or 3 HCV infection received sofosbuvir 400 mg (4 x 100 mg tablets)+PEG+RBV for 12 weeks. |
| Sofosbuvir 100 mg+PEG+RBV | EXPERIMENTAL | Participants received sofosbuvir 100 mg (1 x 100 mg tablet) and placebo to match sofosbuvir (3 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) |
| Sofosbuvir 200 mg+PEG+RBV | EXPERIMENTAL | Participants received sofosbuvir 200 mg (2 x 100 mg tablets) and placebo to match sofosbuvir (2 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) |
| Sofosbuvir 400 mg+PEG+RBV | EXPERIMENTAL | Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) |
| Placebo+PEG+RBV | ACTIVE_COMPARATOR | Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) |
| Name | Type | Description |
|---|---|---|
| Sofosbuvir | DRUG | 400 mg tablet administered orally once daily |
| RBV | DRUG | 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg) |
| PEG | DRUG | Pegylated interferon alfa-2a (Peg-IFNα-2a) 180 µg/0.5 mL pre-filled syringe administered subcutaneously once a week |
| Sofosbuvir/Velpatasvir/Voxilaprevir | DRUG | - |
| Sofosbuvir and Velpatasvir | DRUG | All subjects will receive one film-coated tablet of sofosbuvir/velpatasvir (400/100 mg) orally once daily for 8 weeks. |
| Ribavirin | DRUG | Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg) |
| GS-0938 | DRUG | GS-0938 300 mg (3 × 100 mg tablets) administered orally once daily |
| Placebo to match sofosbuvir | DRUG | Placebo to match sofosbuvir administered orally once daily |
| Placebo to match GS-0938 | DRUG | Placebo to match GS-0938 administered orally once daily |
| Placebo | DRUG | Placebo to match sofosbuvir administered orally once daily |
Inclusion Criteria: * HCV RNA ≥10\^4 IU/mL at screening * Confirmed chronic HCV genotype 1 or 3 infection * HCV treatment naive * Approximately 30% of individuals may have compensated cirrhosis at screening Exclusion Criteria: * Any other chronic liver disease * Infection with hepatitis B virus (...
Sofosbuvir is used to treat chronic hepatitis C virus infection and related conditions, including recurrent chronic HCV. It has also been studied in hepatitis E and acute hepatitis C. It is a small molecule antiviral developed by Gilead Sciences and is given in combination regimens with other direct-acting antivirals.
Sofosbuvir is developed and manufactured by Gilead Sciences, Inc., which trades on the Nasdaq under the ticker GILD. Gilead is the sponsor behind the sofosbuvir clinical trial program, including studies of sofosbuvir combined with velpatasvir and voxilaprevir.
Sofosbuvir has been evaluated in Phase 3 clinical development, with completed Phase 3 and Phase 2 trials in hepatitis C and hepatitis E. Across five tracked trials, four are completed and none are currently active, with total enrollment of about 1,251 participants.
Tracked sofosbuvir trials include NCT02074514, a Phase 3 study of sofosbuvir plus ribavirin in treatment-naive adults with chronic genotype 1 or 3 HCV; NCT02745535, a Phase 2 study of sofosbuvir, velpatasvir, and voxilaprevir in prior DAA-treated patients; NCT03818308 in acute hepatitis C; and NCT03282474 in chronic hepatitis E.
Sofosbuvir is a small molecule direct-acting antiviral that targets the hepatitis C virus NS5B RNA-dependent RNA polymerase, inhibiting viral replication. Its combination partners velpatasvir and voxilaprevir target other HCV proteins, which is why the regimens combine multiple agents against the virus.