Table 5.
AEs of special interest and SAE rates during the Phase III trials, the LONGTERMS extension, and the real-world studies PANGAEA and VIRGILE
| Adverse and serious adverse events | Integrated AEs and SAEs in Phase III clinical trials (n=1,640)17–19 |
LONGTERMS31 (n=3,168) |
PANGAEA32 (n=3,209) |
VIRGILE33 (n=1,023) |
|---|---|---|---|---|
|
| ||||
| n (%) | ||||
| Bradycardia | 6 (0.4) | Unk | 39 (1.2) | 31 (3) |
| First-degree AV block | 26 (2.1)a,b | Unk | 7 (0.2) | Unk |
| Second-degree AV block | 1 (0.1) | 1 (<0.1) | 19 (0.6) | Unk |
| Myocardial infarction | 0 | 2 (0.1) | 0 | Unk |
| Hypertension | 74 (6)a | Unk | 157 (4.9) | 16 (1.6) |
| Infections (unspecified) | 259 (8.2) | Unk | 18 (1.8) | |
| Herpes virus infections | 76 (6) | Unk | Unk | Unk |
| Herpes zoster | Unk | 64 (2) | 80 (2.5) | Unk |
| PML | 0 | 0 | 1 (0.03) | Unk |
| Cryptococcal infection | 0 | Unk | 0 | Unk |
| Fungal | 0 | 23 (0.7) | Unk | Unk |
| Lymphopenia | 196 (12)c | Unk | 402 (12.5) | 20 (2) |
| Hepatic enzymes | 151 (9.2)d | Unk | 183 (5.7) | 18 (1) |
| Macular edema | 3 (0.2) | 2 (0.1) | 17 (0.5) | 7 (0.7) |
| Basal-cell carcinoma | 26 (1.6) | 18 (0.6) | 15 (0.47) | Unk |
| Other carcinomas | 15 (0.9) | 8 (0.2) | 9 (0.3) | Unk |
Notes:
a
Calculated from the 1,212 patients on fingolimod 0.5 mg in the Phase III clinical trials (FREEDOMS, FREEDOMS2, and TRANSFORMS);
b
22 of the 26 events were classified as SAEs during the Phase III trials;
c
number of AEs, of which three (0.2%) were classified as SAEs;
d
number of AEs of which none was classified as an SAE.
Abbreviations: AEs, adverse events; AV, atrioventricular; PML, progressive multifocal leukoencephalopathy; SAE, serious AE; Unk, unknown.