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Sofosbuvir

Phase 3

Hepatitis C | Small molecule | Infectious Disease |Merck & Company, Inc.|Last Updated: Oct 3, 2018

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedACTIVE_CONTROLLEDBiomarker
Total Trials1
Total Enrollment257
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02358044Efficacy and Safety of Combination Grazoprevir (MK-5172)/Elbasvir (MK-8742) Versus Sofosbuvir + Pegylated Interferon + Ribavirin in Hepatitis C Virus Genotype 1, 4 or 6 Infection (MK-5172-077)PHASE3 COMPLETED 257Feb 27, 2015Feb 16, 2016Oct 3, 2018 -
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Study Endpoints
Primary Endpoints
Primary: Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of All Treatment (SVR12)
12 weeks after end of all therapy (Study Week 24)

Hepatitis C Virus ribonucleic acid (HCV-RNA) levels in plasma were measured using the Roche COBAS®AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from each participant. SVR12 was defined as HCV RNA below the lower limit of quantification (\<LLOQ) at 12 weeks after the end of all study therapy. The primary efficacy hypothesis for this study was that the percentage of participants achieving SVR12 in the grazoprevir plus elbasvir arm was non-inferior to the percentage in the SOF plus PR arm. A secondary statistical analysis was performed to determine whether the percentage of participants achieving SVR12 in the grazoprevir plus elbasvir arm was superior to the percentage in the SOF plus PR arm.

Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period Plus First 14 Follow-up Days
Treatment + First 14 days of follow-up (Up to Week 14)

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants who experienced at least one AE was reported for each treatment arm.

Percentage of Participants Discontinuing Study Treatment Due to an AE
Up to Week 12

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants who discontinued study treatment due to an AE was reported for each treatment arm. Participants that discontinued study drug treatment due to an AE may have still continued on trial.

Secondary Endpoints
Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days
Treatment + First 14 days of follow-up (Up to Week 14)
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24)
24 weeks after end of all therapy (Study Week 36)
Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After Ending Study Treatment (SVR4)
4 weeks after end of all therapy (Study Week 16)
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Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Grazoprevir + ElbasvirEXPERIMENTALParticipants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.
SOF + PRACTIVE_COMPARATORParticipants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Interventions
NameTypeDescription
SofosbuvirDRUG400 mg tablets, taken orally (PO) every day (QD) for 12 weeks.
PegIntronBIOLOGICALPegIntron administered subcutaneously every week (QW) at 1.5 mcg/kg for 12 weeks.
RibavirinDRUGCapsule and/or tablet administered PO twice daily (BID) based on weight (1000 - 1200 mg) for 12 weeks.
Grazoprevir/Elbasvir (100 mg/50 mg) FDCDRUGGrazoprevir/Elbasvir (100 mg/50 mg) FDC, taken PO QD for 12 weeks.
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo

Inclusion Criteria: * Weigh ≥40 kg and ≤125 kg * documented chronic HCV GT1, GT4, or GT6 infection * cirrhosis/absence of cirrhosis defined by liver biopsy, Fibroscan, or FibroSure® * either treatment naïve or PR Null Responder, PR Partial Responder, or PR Prior Relapser * participant and partner b...

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Competitive Landscape -Hepatitis C 11 trials