Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Tezacaftor, TEZ
VX-661 · 13 trials · 1 indication
LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
RAESIs included chest discomfort, dyspnea (shortness of breath), respiration abnormal (chest tightness), asthma, bronchial hyperreactivity, bronchospasm, and wheezing.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
The exploratory Brody/CF-CT score semi-quantitatively scores the degree of structural lung disease as shown on CT in participants with CF. The score ranges from a minimum of 0 to a maximum of 219 with higher scores indicating more severe structural lung disease.
MCC was assessed using an imaging technique that enables the tracking of mucus within the airways. MCC was expressed as the percentage of whole-lung clearance through 60 minutes at Baseline and Day 28.
AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of PC Phase.
AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of the OLE Phase.
An AE is defined as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the Informed Consent Form is signed. AE includes serious as well as non-serious AEs. Serious Adverse Event (SAE) is any AE that results in any of the following: death; life-threatening condition; inpatient hospitalization or prolongation of hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; or other important medical event. Treatment-emergent adverse events are defined as adverse events that were reported or worsened on or after start of study drug through the Follow-up Visit (28 days after last dose of study drug) or premature discontinuation.
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
| Arm | Type | Description |
|---|---|---|
| Placebo | OTHER | Participants with genotype F/F received placebo matched to TEZ/IVA fixed dose combination (FDC) in the morning and placebo matched to IVA in the evening for 8 weeks. |
| TEZ/IVA | EXPERIMENTAL | Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks. |
| Ivacaftor | EXPERIMENTAL | Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks. |
| Part A | EXPERIMENTAL | Participants weighing \<25 kg received TEZ 50 mg once daily/IVA 75 mg q12h orally for 14 days. Participants weighing ≥25 kg received TEZ 50 mg once daily/IVA 150 mg q12h orally for 14 days. |
| Part B | EXPERIMENTAL | Participants weighing \<40 kg received TEZ 50 mg/IVA 75 mg as fixed dose combination orally once daily in the morning and IVA 75 mg orally once daily in the evening for 24 weeks. Participants weighing ≥40 kg received TEZ 100 mg/IVA 150 mg as fixed dose combination orally once daily in the morning and IVA 150 mg orally once daily in the evening for 24 weeks. |
| VX-661/IVA | EXPERIMENTAL | VX-661 100 milligram (mg) plus IVA 150 mg fixed dose combination (FDC) tablet administered orally in the morning and IVA 150 mg film-coated tablet administered orally in the evening up to Week 12. |
| VX-661/Ivacaftor combination | EXPERIMENTAL | - |
| Ivacaftor monotherapy | EXPERIMENTAL | - |
| Part 1: Placebo - Cohort 1A and 1B Combined | PLACEBO_COMPARATOR | Participants received placebo matched to VX-440/TEZ/IVA as triple combination for 4 weeks. |
| Part 1 Cohort 1A: Triple Combination (TC) | EXPERIMENTAL | Participants received VX-440 200 milligram (mg) every 12 hours (q12h)/TEZ 100 mg once daily (qd)/IVA 150 mg q12h as triple combination for 4 weeks. |
| Part 1 Cohort 1B: TC Low Dose | EXPERIMENTAL | Participants received VX-440 200 mg q12h/TEZ 50 mg q12h/IVA 150 mg q12h as triple combination for 4 weeks. |
| Part 1 Cohort 1B: TC High Dose | EXPERIMENTAL | Participants received VX-440 600 mg q12h/TEZ 50 mg q12h/IVA 300 mg q12h as triple combination for 4 weeks. |
| Part 2: TEZ/IVA | ACTIVE_COMPARATOR | Following a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received placebo matched to VX-440 and TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period. |
| Part 2: TC-2 | EXPERIMENTAL | Following a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received VX-440 600 mg q12h/ TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period. |
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | EXPERIMENTAL | Participants received VX-661 50 milligram (mg) tablet plus Ivacaftor (IVA) 150 mg tablet every 12 hours (q12h) for 12 weeks. |
| PC Phase: VX 661 placebo q12h + IVA placebo q12h | PLACEBO_COMPARATOR | Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. |
| PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | EXPERIMENTAL | Participants received two VX-661 50 mg tablets once daily (qd) plus IVA 150 mg tablet q12h for 12 weeks. |
| PC Phase: VX -661 placebo qd + IVA placebo q12h | PLACEBO_COMPARATOR | Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. |
| OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h | EXPERIMENTAL | Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase. |
| Group 1-6d Combined: Placebo | PLACEBO_COMPARATOR | All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a, 5b, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days. |
| Group 1: VX-661 10 mg qd | EXPERIMENTAL | All participants in group 1 who received VX-661 10 milligram (mg) tablet orally once daily (qd) for up to 28 days. |
| Group 2a: VX-661 30 mg qd | EXPERIMENTAL | All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet every 12 hours (q12h) for up to 28 days. |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | EXPERIMENTAL | All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days. |
| Group 3a: VX-661 100 mg qd | EXPERIMENTAL | All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days. |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | EXPERIMENTAL | All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days. |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | EXPERIMENTAL | All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days. |
| Group 5a: VX-661 150 mg qd | EXPERIMENTAL | All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days. |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | EXPERIMENTAL | All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days. |
| Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h | EXPERIMENTAL | All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days. |
| Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h | EXPERIMENTAL | All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days. |
| Group 7: Placebo | PLACEBO_COMPARATOR | All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco (Ivacaftor) for up to 28 days. |
| Group 7: VX-661 100 mg qd | EXPERIMENTAL | All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco (Ivacaftor) for up to 28 days. |
| Name | Type | Description |
|---|---|---|
| TEZ/IVA | DRUG | Participants weighing \<40 kg received TEZ 50 mg/IVA 75 mg FDC tablet and those weighing ≥40 kg received TEZ 100 mg/IVA 150 mg FDC tablet. |
| IVA | DRUG | Participants weighing \<40 kg IVA 75 mg tablet and those weighing ≥40 kg received IVA 150 mg tablet. |
| Placebo | DRUG | Placebo matched to TEZ/IVA FDC |
| Tezacaftor/Ivacaftor | DRUG | TEZ 100 mg/IVA 150 mg fixed-dose combination tablet. |
| Ivacaftor | DRUG | IVA 150 mg tablet. |
| TEZ | DRUG | - |
| VX-661 plus ivacaftor combination | DRUG | - |
| Placebo (matched to VX-661 plus ivacaftor combination) | DRUG | - |
| Placebo (matched to ivacaftor) | DRUG | - |
| VX-661/Ivacaftor | DRUG | Fixed dose combination tablet, oral use |
| Placebo matched to VX-661/ ivacaftor | DRUG | Fixed dose combination tablet, oral use |
| Placebo matched to Ivacaftor | DRUG | Tablet, oral use |
| VX-661 Plus Ivacaftor Combination Placebo | DRUG | FDC tablet, oral use |
| Ivacaftor placebo | DRUG | Tablet, oral use |
| VX-440 | DRUG | - |
| Matched Placebo | DRUG | - |
| Tezacaftor/Ivacaftor matching placebo | DRUG | - |
| Ivacaftor matching placebo | DRUG | - |
| VX-661 | DRUG | Tablet, oral use |
| Placebo matched to VX-661 | DRUG | Tablet, oral use |
Key Inclusion Criteria: * Homozygous for F508del or heterozygous for F508del and an RF mutation (as defined in the protocol). * Participants with ppFEV1 of ≥70 percentage points adjusted for age, sex, height. * Participants with a screening LCI2.5 result ≥7.5. * Participants who are able to swallow...
Top 6 of 7 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Vertex Pharmaceuticals Incorporated | VRTX | 8 | PHASE3 | Alyftrek, Trikafta, Ivacaftor, VX-581, VX-272 |
| BiomX Inc. | PHGE | 1 | PHASE2 | BX004 |
| 4D Molecular Therapeutics, Inc. | FDMT | 1 | PHASE2 | 4D-710 |
| Arcturus Therapeutics Holdings, Inc. | ARCT | 1 | PHASE2 | ARCT-032 |
| Krystal Biotech, Inc. | KRYS | 1 | PHASE1 | KB407 |
| Roivant Sciences Ltd. | ROIV | 1 | PHASE1 | SP-101 |
VX-661 is an investigational small molecule developed for the treatment of cystic fibrosis. It is studied in combination with ivacaftor in patients aged 12 years and older who have specific CFTR mutations, including those heterozygous or homozygous for the F508del-CFTR mutation. It remains in clinical development and is not approved.
VX-661 targets CFTR, the cystic fibrosis transmembrane conductance regulator protein. It is a small molecule designed to act on this protein, which is defective in cystic fibrosis. In clinical studies it is given in combination with ivacaftor, another CFTR-directed therapy.
VX-661 is being developed by Vertex Pharmaceuticals Incorporated, which trades on the Nasdaq under the ticker VRTX. Vertex is the sponsor of the Phase 2 and Phase 3 cystic fibrosis studies of VX-661 given in combination with ivacaftor.
VX-661 is in Phase 3 development for cystic fibrosis. Five clinical trials of the program have been completed, including Phase 3 studies, and no trials are currently active. VX-661 is investigational and has not been approved by the FDA.
Completed trials of VX-661 in cystic fibrosis include NCT02516410, NCT02392234, and NCT02347657, all Phase 3, plus the Phase 2 study NCT02070744. These randomized, double-blind, placebo-controlled studies enrolled patients aged 12 years and older across North America, Europe, and Israel.