TABLE 2.
Summary of safety data from long‐term asthma trials and other non‐asthma Phase III trials
| COSMOS (open label a ) 125 | COLUMBA (open label b ) 16 | COSMEX (open label c ) 15 | MIRRA 64 | 200622 82 | SYNAPSE 101 (safety population) | METREX 121 (safety population with an eosinophilic phenotype d ) | METREO 121 (safety population) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mepo 100 mg SC every 4 weeks for 52 weeks plus asthma SoC (N = 651) | Mepo 100 mg SC every 4 weeks plus asthma SoC (N = 347) | Mepo 100 mg SC every 4 weeks plus asthma SoC (N = 339) | Mepo 300 mg SC (N = 68) | Placebo (N = 68) | Mepo 300 mg SC (N = 54) | Placebo (N = 54) | Mepo 100 mg SC (N = 206) | Placebo (N = 201) | Mepo 100 mg SC (N = 233) | Placebo (N = 229) | Mepo 100 mg SC (N = 223) | Mepo 300 mg SC (N = 225) | Placebo (N = 226) | |
| Every 4 weeks for 52 weeks plus EGPA SoC | Every 4 weeks for 32 weeks plus HES SoC | Every 4 weeks for 52 weeks plus CRSwNP SoC | Every 4 weeks for 52 weeks plus COPD SoC | |||||||||||
| Any on‐treatment AEs | 558 (86) | 326 (94) | 315 (93) | 66 (97) | 64 (94) | 48 (89) | 47 (87) | 169 (82) | 168 (84) | 190 (82) | 189 (83) | 191 (86) | 196 (87) | 185 (82) |
| Treatment‐related AE | 123 (19) | 97 (28) | 51 (15) | 35 (51) | 24 (35) | 12 (22) | 7 (13) | 30 (15) | 19 (9) | – | – | – | – | – |
| Leading to study withdrawal | 11 (<2) | 19 (5) | 4 (1) | 2 (3) | 1 (1) | 1 (2) | 2 (4) | 0 | 1 (<1) | 7 (3) | 10 (4) | 7 (3) | 13 (6) | 18 (8) |
| Any on‐treatment SAE, n (%) | 94 (14) | 79 (23) | 84 (25) | 12 (18) | 18 (26) | 10 (19) | 8 (15) | 12 (6) | 13 (6) | 65 (28) | 80 (35) | 57 (26) | 60 (27) | 68 (30) |
| Treatment‐related SAE | 2 (<1) | 2 (<1) | 3 (0.9) | 3 (4) | 3 (4) | 0 | 0 | 0 | 1 (<1) | – | – | – | – | – |
| Any fatal SAE | 0 | 6 (2) e | 2 (<1) e | 1 (1) e | 0 | 1 (2) e | 0 | 0 | 1 (<1) | 6 (3) e | 8 (3) | 4 (2) e | 8 (4) e | 9 (4) |
| Any systemic reaction | 13 (2) | 9 (3) | 2 (0.6) | 4 (6) | 1 (1) | 1 (2) | 0 | 2 (<1) | 1 (<1) | 3 (1) | 4 (2) | 3 (1) | 5 (2) | 4 (2) |
| Local injection‐site reaction | 29 (4) | 42 (12) | 14 (4) | 10 (15) | 9 (13) | 4 (7) | 2 (4) | 5 (2) | 2 (<1) | 7 (3) | 7 (3) | 6 (3) | 11 (5) | 10 (4) |
| Immunogenicity (presence of anti‐mepolizumab antibodies) in patients tested | 31 (5) | 1/346 (8) | 6/335 (2) | 0 | 0 | 1 (<1) | 0 | 6 (3) | 3 (<1) | 14/395 (4) | 2/395 (2) | 13/220 (6) | 4/220 (2) | 3/217 (1) |
| Serious infections | – | 17 (5) | 20 (6) | – | – | – | – | – | – | – | – | – | – | – |
| Malignancies | – | 6 (2) | 8 (2) | – | – | 1 (2) | 0 | – | – | – | – | – | – | – |
Data are given as number (%) of patients unless otherwise noted.
Abbreviations: AE, adverse event; COPD, chronic obstructive pulmonary disease; CRSwNP, chronic rhinosinusitis with nasal polyposis; EGPA, eosinophilic granulomatosis with polyangiitis; HES, hypereosinophilic syndrome; IV, intravenous; mepo, mepolizumab; NP, nasal polyposis; SAE, serious adverse event; SC, subcutaneous; SoC, standard of care.
Eligible patients in the COSMOS open‐label extension study had completed either the MENSA or SIRIUS double‐blind studies and were treated with mepolizumab regardless of treatment allocation in the prior studies.
Eligible patients in the COLUMBA open‐label extension study had to have been randomized and received at least 2 doses of treatment (mepolizumab or placebo) in the DREAM study had received an asthma controller medication for ≥12 weeks before enrollment in COLUMBA. Mepolizumab treatment was administered until a protocol‐defined stopping criterion was met.
Patients were enrolled from the COSMEX open‐label extension study and had to have the most severe forms of severe eosinophilic asthma (eg, a history of life‐threatening or seriously debilitating asthma, the full definitions of which are noted in the COSMEX publication), have been receiving ICS controller therapy for the last 8 months, and had to have previously demonstrated a protocol‐defined clinical benefit with mepolizumab treatment. The study completed after all patients met a protocol‐defined discontinuation criterion.
The METREX safety population with an eosinophilic phenotype included patients with blood eosinophil count of ≥150 cells/µl at screening or ≥300 cells/µl within the previous year.
Fatalities were not considered related to mepolizumab treatment.