Table 2.
Overview of the key endpoints from the alemtuzumab clinical trial program
| CAMMS223 extension [13, 20] | CARE-MS I [8, 11, 17, 18, 33, 34] | CARE-MS I extension [8, 17, 18] | CARE-MS II [7, 12, 17, 19, 35] | CARE-MS II extension [7, 19] | ||||
|---|---|---|---|---|---|---|---|---|
| 5-year data | Study duration: 2 years | Year 4 | Study duration: 2 years | Year 4 | ||||
| SC IFNβ-1a 44 µg TIW |
Alemtuzumab 12 mg/day |
SC IFNβ-1a 44 µg TIW |
Alemtuzumab 12 mg/day |
Alemtuzumab 12 mg/day |
SC IFNβ-1a 44 µg TIW |
Alemtuzumab 12 mg/day |
Alemtuzumab 12 mg/day |
|
| Patients entering study, N | 111 | 112 | 187 | 376 | 349 | 202 | 426 | 393 |
| Clinical endpoints | ||||||||
| ARR | 0.35 | 0.12 | 0.39 | 0.18 | 0.14 | 0.52 | 0.26 | 0.23 |
| ARR relative reduction (alemtuzumab vs. SC IFNβ-1a), % | 66 (p < 0.0001) | 55 (p < 0.0001) | 49 (p < 0.0001) | |||||
| Relapse-free patients,a % | 41 | 68 | 59 | 78 (p < 0.0001) | 87 | 47 | 65 (p < 0.0001) | 79 |
| Patients with 6-month CDW,a % | 38 | 16 | 11 | 8 | 17 (years 0−4) | 21 | 13 | 24 (years 0−4) |
| CDW relative risk reduction (alemtuzumab vs. SC IFNβ-1a), % | 69 (p = 0.0005) | 30 (p = 0.22)b | 42 (p = 0.0084) | |||||
| Patients with 6-month CDI,a % | N/A | N/A | 27c | 23 (p = 0.5192)c |
30 (years 0–4) |
13 | 29 (p = 0.0002) |
41 (years 0–4) |
| Mean change in EDSS score from baseline | 0.46 | −0.15 (p = 0.0056) |
−0.14 | −0.14 (p = 0.97) | −0.09 (years 0–4) |
0.24 | −0.17 (p < 0.0001) | 0.00 (years 0–4) |
| MRI endpoints | ||||||||
| Gd+ lesion free, % | 81 | 93 (p < 0.0001) | 87 | 78 | 91 (p < 0.0001) | 89 | ||
| New/enlarging T2 lesion free, % | 60 | 78 (p < 0.0001) | 71 | 48 | 76 (p < 0.0001) | 70 | ||
| New T1 hypointense lesion free, % | 82 | 93 (p = 0.0001) | 85 | 74 | 93 (p < 0.0001) | 86 | ||
| MRI activity free,d % | 59 | 77 (p < 0.0001) | 70 | 47 | 76 (p < 0.0001) | 70 | ||
| Brain volume change | ||||||||
| Median BPF change, % (95% CI) | –1.49 | −0.87 (p < 0.0001) (years 0–2) |
−1.134c
(years 0–4) |
–0.81 | –0.62 (p = 0.0012) (years 0–2) |
−0.882c
(years 0–4) |
||
| Reduction in rate of brain volume loss, % | 42 | 24 | ||||||
| Disease-free survival | ||||||||
| Patients with NEDA,e % | 27 | 39 | 60 | 14 | 32 | 55 | ||
| Odds ratio | 1.75 (p = 0.006) | 3.03 (p < 0.0001) | – | |||||
| Retreatment | ||||||||
| Patients not requiring retreatment, % | N/A | 94% | N/A | N/A | 74 | N/A | N/A | 68 |
ARR annualized relapse rate, BPF brain parenchymal fraction, CI confidence interval, CDI confirmed disability improvement, CDW confirmed disability worsening, EDSS Expanded Disability Status Scale, Gd + gadolinium-enhancing, IFN interferon, MRI magnetic resonance imaging, N/A not applicable, NEDA no evidence of disease activity, SC subcutaneous, TIW three times per week
aKaplan–Meier estimates
bWhen CAMMS223 and CARE-MS I data were pooled, a significant reduction in risk of 6-month CDW (50%, p = 0.0029), as well as ARR (56%, p < 0.0001) was observed, when compared with SC IFNβ-1a [36]
cSanofi Genzyme, data on file
dMRI activity-free was defined as the absence of both Gd+ lesions and new or enlarging T2-hyperintense lesions; clinical disease activity-free was defined as the absence both of relapses and 6-month CDW [8]
ePre-specified tertiary endpoint in CARE-MS I and II. NEDA was defined as patients who were MRI and clinically disease free [8]. NEDA values are per year. For CARE-MS II, the denominator for the percentage of patients with each type of event is the total number of patients with MRIs performed at the given time point (Sanofi Genzyme, data on file)