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VX-659

Phase 3

Cystic Fibrosis | Small molecule | Respiratory |Vertex Pharmaceuticals Incorporated|Last Updated: Apr 22, 2021

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
RandomizedDouble-BlindCONTROLLEDDMCBiomarker
Total Trials4
Total Enrollment788
FDA Designations
No designations recorded
Clinical Trials (4)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03460990A Study of VX-659 Combination Therapy in CF Subjects Homozygous for F508del (F/F)PHASE3 COMPLETED 116May 1, 2018Oct 8, 2018Oct 17, 201946 United States, Australia +4
NCT03447249A Phase 3 Study of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)PHASE3 COMPLETED 385Mar 7, 2018Feb 5, 2019Mar 13, 2020101 United States, Australia +9
NCT03224351A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic FibrosisPHASE2 COMPLETED 124Aug 8, 2017Feb 28, 2018Apr 22, 202147 United States, Ireland +2
NCT03029455A Study to Evaluate Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Adults With Cystic FibrosisPHASE1 COMPLETED 163Nov 1, 2016Aug 1, 2017Sep 5, 201710 United Kingdom
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Study Endpoints
Primary Endpoints
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
From Baseline at Week 4

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)
Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs)
from baseline up to Day 50
Secondary Endpoints
Absolute Change in Sweat Chloride (SwCl)
From Baseline at Week 4
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
From Baseline at Week 4
Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
TEZ/IVAACTIVE_COMPARATORFollowing a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.
VX-659/TEZ/IVA TCEXPERIMENTALFollowing a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
PlaceboPLACEBO_COMPARATORParticipants who received placebo matched to VX-659/TEZ/IVA for 24 weeks in the TC treatment period.
Part 1: PlaceboPLACEBO_COMPARATORParticipants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched TEZ/IVA in washout period for 4 days.
Part 1: VX-659/TEZ/IVA TC - Low DoseEXPERIMENTALParticipants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Part 1: VX-659/TEZ/IVA TC - Medium DoseEXPERIMENTALParticipants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Part 1: VX-659/TEZ/IVA TC - High DoseEXPERIMENTALParticipants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Part 2: TEZ/IVAACTIVE_COMPARATORFollowing run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.
Part 2: VX-659/TEZ/IVA TCEXPERIMENTALFollowing run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.
Part 3: PlaceboPLACEBO_COMPARATORParticipants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
Part 3: VX-659/TEZ/VX-561 TCEXPERIMENTALParticipants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
Part A: VX-659 or Matching PlaceboEXPERIMENTALPart A includes single-dose escalation.
Part B: VX-659 or Matching PlaceboEXPERIMENTALPart B includes multiple-dose escalation.
Part C: VX-659 in TC with TEZ/IVA or Matching Triple PlaceboEXPERIMENTALPart C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).
Part D: VX-659 in TC with TEZ/IVA or Matching Triple PlaceboEXPERIMENTALPart D includes subjects with CF. Participants will receive TC or matching placebos.
Interventions
NameTypeDescription
VX-659/TEZ/IVADRUGParticipants received VX-659/TEZ/IVA orally once daily in the morning.
TEZ/IVADRUGParticipants received TEZ/IVA orally once daily in the morning.
IVADRUGParticipants received IVA orally once daily in the evening.
PlaceboDRUGParticipants received placebo matched TEZ/IVA orally once daily in the morning.
VX-659DRUGTablet for oral administration.
Placebo (matched to VX-659/TEZ/IVA)DRUGPlacebo matched to VX-659 and TEZ/IVA.
TEZDRUGTablet for oral administration.
VX-561DRUGTablet for oral administration.
Placebo (matched to VX-659/TEZ/VX-561)DRUGPlacebo matched to VX-659, TEZ and VX-561.
TezacaftorDRUG -
IvacaftorDRUG -
VX-659 Matching PlaceboDRUG -
Triple Combination (TC) Matching PlacebosDRUG -
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Eligibility Criteria
Age Range12 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites46

Key Inclusion Criteria: * Homozygous for the F508del mutation (F/F) * Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height Key Exclusion Criteria: * Clinically significant cirrhosis with or without portal hypertension * Lung infection with org...

Countries:United StatesAustraliaGermanyIrelandSpainUnited KingdomCanadaDenmarkIsraelPolandSwitzerland
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