Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with acute or chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). FDA label
Also known as Glecaprevir, ABT-530, MAVYRET
ABT-493 · 15 trials · 12 indications
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of study drug. The primary efficacy endpoint was non-inferiority of the ABT-493/ABT-530 8-week regimen (Arm A) to the sofosbuvir and ribavirin 12 week regimen (Arm B) in SVR12 using a non-inferiority margin of 10% in the intent-to-treat (ITT) population.
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of study drug.
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of study drug.
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\] 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority in the percentage of participants achieving SVR12 of the 12-week regimen (Arm A) to the standard of care (Arm B: 12 weeks of treatment with sofosbuvir \[SOF\] + daclatasvir \[DCV\]), defined as: a) the lower bound of the 95% confidence interval (CI) for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was greater than 92%; OR b) the lower bound of the 95% CI for the difference was below the non-inferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm A was greater than 92%; OR c) the lower bound of the 97.5% CI for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was below 92%.
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. If the first primary efficacy objective (noninferiority of Arm A to Arm B) was achieved, then the second primary efficacy objective, noninferiority in the percentage of participants achieving SVR12 of the 8-week regimen (Arm C) to the 12-week regimen (Arm A) was to be tested. Noninferiority was defined as: a) the lower bound of the 95% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was greater than 92%, OR b) the lower bound of the 95% CI for the difference was below the noninferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm C was greater than 92%, OR c) the lower bound of the 97.5% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was below 92%.
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of active study drug. The primary efficacy endpoint was the noninferiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior sofosbuvir (SOF) + ribavirin (RBV) ± pegylatedinterferon (pegIFN) failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks).
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 in the 12-week treatment group compared with the historical control rate for HCV GT1 subjects who are treatment-naïve or treated with pegylated-interferon alfa-2a or alfa-2b and ribavirin (pegIFN/RBV).
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants (excluding those who discontinued/experienced virologic failure by Week 8 or had no HCV RNA value at Week 12 or later) who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm.
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm.
Maintaining a sustained virologic response (SVR) is defined as having Hepatitis C virus ribonucleic acid (HCV RNA) value consistently below the lower limit of quantification (\< LLOQ) from the end of treatment in the previous study throughout Study M13-576 (this study).
Relapse was defined as confirmed Hepatitis C virus ribonucleic acid (HCV RNA) greater than or equal to the lower limit of quantification (≥ LLOQ) between end of treatment and up to and including the last HCV RNA measurement collected in this study for a participant with HCV RNA \< LLOQ at Final Treatment Visit who completed treatment, excluding reinfection. HCV reinfection was defined as confirmed HCV RNA ≥ LLOQ after the end of treatment in a participant who had HCV RNA \< LLOQ at Final Treatment Visit, along with the post-treatment detection of a different HCV genotype, subtype, or clade compared with baseline, as determined by phylogenetic analysis of the NS3 or NS5A, and/or NS5B gene sequences.
Plasma samples for HCV resistance testing were collected at study visits. The variants in nonstructural viral protein 3 (NS3) and nonstructural viral protein 5A (NS5A) at amino acid positions of interest were analyzed by next generation sequencing relative to baseline and prototypic reference sequences.
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of study drug.
The percentage of participants with sustained virologic response (plasma hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of study drug.
Maximal decrease from baseline in log10 HCV RNA levels during ABT-493 or ABT-530 monotherapy treatment. The baseline value was the last measurement before the first dose of monotherapy on Day 1.
The AUC from time 0 to infinity represents the total drug exposure over time.
Measurement of safety parameters include physical examinations, clinical laboratory tests, 12-lead ECGs (electrocardiograms) and vital signs.
Total number of subjects with adverse events.
The peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
AUC reflects the actual body exposure to drug after administration of a dose of the drug.
The AUC from time 0 to infinity represents the total drug exposure over time.
The peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
AUC reflects the actual body exposure to drug after administration of a dose of the drug.
The AUC during hemodialysis represents the total drug exposure over time.
The AUC during hemodialysis represents the total drug exposure over time.
Pharmacokinetic parameter values include the maximum plasma concentration (Cmax), the terminal phase elimination rate constant (B), the area under the plasma concentration-time curve (AUC) from time 0 to time of the last measurable concentration (AUCt).
| Arm | Type | Description |
|---|---|---|
| Arm A | EXPERIMENTAL | Co-formulated ABT-493/ABT-530 (300 mg/120 mg) administered once daily (QD) for 8 weeks in HCV genotype (GT) 2 -infected, DAA treatment-naïve participants without cirrhosis. |
| Arm B | ACTIVE_COMPARATOR | sofosbuvir (400 mg) QD co-administered with weight based ribavirin (RBV) 600-1000 mg divided twice daily (BID) for 12 weeks in HCV GT2 -infected, DAA treatment-naïve participants without cirrhosis. |
| Arm C | EXPERIMENTAL | ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120mg) QD for 12 weeks in HCV GT1- or GT2-infected participants with compensated cirrhosis, HCV GT3-, 4-, 5- and 6-infected participants (with compensated cirrhosis or without cirrhosis), HCV GT1- and GT2-infected participants who had failed prior DAA treatments (with compensated cirrhosis or without cirrhosis), and HCV GT1- or GT2-infected participants with severe renal impairment and compensated cirrhosis. |
| Arm D | EXPERIMENTAL | ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in GT1- or GT2-infected participants with severe renal impairment and without cirrhosis. |
| ABT-493/ABT-530 | EXPERIMENTAL | ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. |
| Arm A DB Active Drug | EXPERIMENTAL | ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind \[DB\] treatment period) |
| Arm B DB Placebo | EXPERIMENTAL | Placebo for ABT-493/ABT-530 QD for 12 weeks (DB treatment period) |
| Arm B OL Active Drug | EXPERIMENTAL | ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (open-label \[OL\] treatment period) |
| ABT-493/ABT-530 for 12 weeks | EXPERIMENTAL | ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. |
| ABT-493/ABT-530 for 8 weeks | EXPERIMENTAL | ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks. |
| HCV-infected Participants | NO_INTERVENTION | Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study. |
| Arm E | EXPERIMENTAL | ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 16 weeks in HCV genotype 1- or 4-6- infected participants with or without cirrhosis. |
| Arm F | EXPERIMENTAL | ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD and weight-based ribavirin (RBV) divided BID for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis. |
| Arm G | EXPERIMENTAL | ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (40 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis. |
| Arm H | EXPERIMENTAL | ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis. |
| Arm I | EXPERIMENTAL | ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (40 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis. |
| Arm J | EXPERIMENTAL | ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis. |
| Arm K | EXPERIMENTAL | ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis. |
| Arm L | EXPERIMENTAL | ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT3 -infected treatment naïve and for 12 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis. |
| Arm M | EXPERIMENTAL | ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (80 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve participants with compensated cirrhosis. |
| Arm N | EXPERIMENTAL | ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (80 mg) QD and ribavirin (RBV) (800 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve participants with compensated cirrhosis. |
| Arm O | EXPERIMENTAL | ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve participants with compensated cirrhosis and for 16 weeks in HCV GT3 -infected treatment-experienced participants with compensated cirrhosis. |
| Arm P | EXPERIMENTAL | ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD and RBV (800 mg) QD for 12 weeks in HCV GT3-infected treatment naïve and treatment-experienced participants with compensated cirrhosis. |
| Arm Q1 | EXPERIMENTAL | ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment naïve participants with cirrhosis. |
| Arm Q2 | EXPERIMENTAL | ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis. |
| Arm R1 | EXPERIMENTAL | ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis. |
| Arm R2 | EXPERIMENTAL | ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants with cirrhosis. |
| Arm S1 | EXPERIMENTAL | ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT2 infected treatment naïve and treatment experienced participants without cirrhosis. |
| Arm S2 | EXPERIMENTAL | ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT4-6 infected treatment naïve and treatment experienced participants without cirrhosis. |
| Arm 1 Non-cirrhotic | EXPERIMENTAL | ABT-493 Dose A (100 mg once daily \[QD\]) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Arm 2 Non-cirrhotic | EXPERIMENTAL | ABT-493 Dose B (400 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Arm 3 Non-cirrhotic | EXPERIMENTAL | ABT-493 Dose C (700 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Arm 4 Non-cirrhotic | EXPERIMENTAL | ABT-493 Dose D (200 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Arm 5 Compensated cirrhotic | EXPERIMENTAL | ABT-493 Dose E (200 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Arm 6 Non-cirrhotic | EXPERIMENTAL | ABT-530 Dose A (15 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Arm 7 Non-cirrhotic | EXPERIMENTAL | ABT-530 Dose B (120 mg QD) for 3 days,followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Arm 8 Non-cirrhotic | EXPERIMENTAL | ABT-530 Dose C (400 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Arm 9 Non-cirrhotic | EXPERIMENTAL | ABT-530 Dose D (40 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Arm 10 Compensated cirrhotic | EXPERIMENTAL | ABT-530 Dose E (120 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Arm 11 Non-cirrhotic | EXPERIMENTAL | ABT-493 Dose F (300 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Arm 12 Non-cirrhotic | EXPERIMENTAL | ABT-530 Dose F (≤ 400 mg) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| Group 1 - Mild Renal Impairment | EXPERIMENTAL | Subjects with mild renal impairment. eGFR (by MDRD equation) range 60 - 89 mL/min/1.73 m2 as determined at Screening. |
| Group 2 - Moderate Renal Impairment | EXPERIMENTAL | Subjects with moderate renal impairment. eGFR (by MDRD equation) range 30 - 59 mL/min/1.73 m2 as determined at Screening. |
| Group 3 - Severe Renal Impairment | EXPERIMENTAL | Subjects with severe renal impairment. eGFR (by MDRD equation) range 15 - 29 mL/min/1.73 m2 as determined at Screening. |
| Group 4 - End Stage Renal Disease, Not Yet on Dialysis | EXPERIMENTAL | Subjects with end stage renal disease, not yet on dialysis. eGFR (by MDRD equation) range \< 15 mL/min/1.73 m2 as determined at Screening. |
| Group 5 - Normal Renal Function | EXPERIMENTAL | Subjects with normal renal function. eGFR (by MDRD equation) range ≥ 90 mL/min/1.73 m2 as determined at Screening. |
| Group 6 - End Stage Renal Disease, Requiring Dialysis. | EXPERIMENTAL | Subjects with end stage renal disease, requiring dialysis. eGFR (by MDRD equation) \< 15 mL/min/1.73 m2 as determined at Screening. |
| Group I | EXPERIMENTAL | Subjects with mild hepatic impairment |
| Group II | EXPERIMENTAL | Subjects with moderate hepatic impairment |
| Group III | EXPERIMENTAL | Subjects with severe hepatic impairment |
| Group IV | EXPERIMENTAL | Subjects with normal hepatic function |
| Name | Type | Description |
|---|---|---|
| ABT-493/ABT-530 | DRUG | Co-formulated tablet |
| sofosbuvir (SOF) | DRUG | Tablet |
| ribavirin (RBV) | DRUG | Capsule |
| OBV/PTV/r | DRUG | Co-formulated tablet |
| Sofosbuvir | DRUG | Tablet |
| Daclatasvir | DRUG | Tablet |
| Placebo for ABT-493/ABT-530 | DRUG | tablet |
| ABT-493 | DRUG | ABT-493 was not administered in this study. This study was a follow-up for participants who received the drug in prior studies. |
| ABT-530 | DRUG | ABT-530 was not administered in this study. This study was a follow-up for participants who received the drug in prior studies. |
| ABT-493, ABT-530 | DRUG | ABT-493 (tablet) dosed with ABT-530 (tablet) |
| ABT-450/r/ABT-267, ABT-333 | DRUG | Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet |
Inclusion Criteria: * Females were postmenopausal for at least 2 years prior to screening; surgically sterile or had a vasectomized partner; or, if of childbearing potential and sexually active with a male partner, were currently using at least 1 effective method of birth control at the time of Scr...
ABT-493 is an investigational small molecule developed for the treatment of chronic hepatitis C virus (HCV) infection. Studies have covered adults with HCV genotypes 1 through 6, including patients with compensated cirrhosis, renal impairment, and Japanese adults with genotype 2 chronic HCV.
ABT-493 is being developed by AbbVie Inc., which trades on the New York Stock Exchange under the ticker ABBV. AbbVie sponsored the Phase 3 clinical program evaluating ABT-493 in adults with chronic hepatitis C virus infection across multiple patient populations.
ABT-493 is in Phase 3 clinical development. Six Phase 3 trials have been completed, with no active trials currently listed. The program enrolled a total of 2,307 participants across controlled, randomized studies in chronic hepatitis C virus infection.
ABT-493 has been studied in six completed Phase 3 trials, including NCT02723084 in Japanese adults with genotype 2 chronic HCV, NCT02707952 in Japanese adults with chronic HCV, NCT02651194 in renally impaired adults with HCV genotypes 1 through 6, and NCT02642432 in adults with HCV genotypes 1, 2, 4, 5, or 6 and compensated cirrhosis.
ABT-493 and ABT-530 are distinct compounds that are studied together as a combination regimen, referred to as ABT-493/ABT-530. The Phase 3 trials listed evaluate this combination in adults with chronic hepatitis C virus infection, so searches for ABT-493, ABT-530, or ABT-493/ABT-530 refer to the same development program.