Table 1.
Adverse Events
| OLE Study (N = 506; Mean Duration of Exposure: 37.2 wk) |
F/MF Pivotal Study* ELX/TEZ/IVA Arm (n = 202; Mean Duration of Exposure: 23.6 wk) |
|||
|---|---|---|---|---|
| Participants with AEs [n (%)] | Event Rate per 100 Participant-Years | Participants with AEs [n (%)] | Event Rate per 100 Participant-Years | |
| Any AE | 471 (93.1) | 739.9 | 188 (93.1) | 1,096.0 |
| AEs by maximum severity | ||||
| Mild | 180 (35.6) | ND | 67 (33.2) | ND |
| Moderate | 238 (47.0) | ND | 102 (50.5) | ND |
| Severe | 51 (10.1) | ND | 19 (9.4) | ND |
| Life-threatening† | 2 (0.4) | ND | 0 | ND |
| AEs leading to treatment discontinuation | 7 (1.4) | 3.3 | 2 (1.0) | 3.0 |
| AEs leading to treatment interruption | 29 (5.7) | 13.7 | 19 (9.4) | 26.0 |
| AEs leading to death | 0 | 0 | 0 | 0 |
| Most common AEs in the OLE study (occurring in ≥10% of participants) | ||||
| Infective pulmonary exacerbation of CF | 127 (25.1) | 49.6 | 44 (21.8) | 64.9 |
| Cough | 118 (23.3) | 44.3 | 34 (16.8) | 38.9 |
| Oropharyngeal pain | 74 (14.6) | 25.7 | 20 (9.9) | 27.0 |
| Nasopharyngitis | 69 (13.6) | 21.6 | 22 (10.9) | 30.0 |
| Headache | 66 (13.0) | 24.9 | 35 (17.3) | 48.9 |
| Sputum increased | 63 (12.5) | 20.6 | 40 (19.8) | 46.9 |
| Upper respiratory tract infection | 60 (11.9) | 18.3 | 24 (11.9) | 30.0 |
| Fatigue | 51 (10.1) | 16.3 | 9 (4.5) | 9.0 |
| SAEs | 80 (15.8) | 27.5 | 28 (13.9) | 36.9 |
| Most common SAEs (occurring in ≥1% of participants) | ||||
| Infective pulmonary exacerbation of CF | 42 (8.3) | 12.2 | 11 (5.4) | 12.0 |
| Hemoptysis | 5 (1.0) | 1.5 | 2 (1.0) | 2.0 |
| Distal intestinal obstruction syndrome | 5 (1.0) | 1.5 | 1 (0.5) | 1.0 |
| Any rash event | 50 (9.9) | 15.8 | 22 (10.9) | 30.0 |
| SAEs | 1 (0.2) | 0.3 | 3 (1.5) | 3.0 |
| Leading to treatment interruption | 5 (1.0) | 1.3 | 4 (2.0) | 4.0 |
| Leading to treatment discontinuation | 1 (0.2) | 0.3 | 1 (0.5) | 1.0 |
| ALT or AST increase‡ | ||||
| >3× to ≤5× ULN | 21 (4.2) | ND | 11 (5.4) | ND |
| >5× to ≤8× ULN | 8 (1.6) | ND | 2 (1.0) | ND |
| >8× ULN | 3 (0.6) | ND | 3 (1.5) | ND |
| Elevated transaminase AEs‡ | ||||
| Any AEs | 36 (7.1) | 16.5 | 22 (10.9) | 42.9 |
| SAEs | 2 (0.4) | 1.0 | 0 | 0 |
| Leading to treatment interruption | 11 (2.2) | 5.1 | 2 (1.0) | 3.0 |
| Leading to treatment discontinuation | 3 (0.6) | 1.5 | 0 | 0 |
Definition of abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CF = cystic fibrosis; ELX = elexacaftor; F/MF = heterozygous for the F508del-CFTR mutation and a minimal function CFTR mutation; IVA = ivacaftor; ND = not determined; OLE = open-label extension; SAE = serious adverse event; TEZ = tezacaftor; ULN = upper limit of normal.
Some of the data from the F/MF pivotal study were previously published (5) but are provided here for comparison.
The life-threatening AEs were a suicide attempt and a pulmonary hemorrhage.
In the placebo arm of the F/MF pivotal study, 8 (4.0%) participants had an elevated transaminase AE. Laboratory elevations in ALT or AST of >3× to ≤5× ULN, >5× to ≤8× ULN, and >8× ULN were seen in 8 (4.0%), 1 (0.5%), and 2 (1.0%) participants, respectively.