Table 2.
Efficacy of New and Emerging Monoclonal Therapies.
| Therapy | Trial | Design | MS Type | Key Outcome Measures |
|---|---|---|---|---|
| Alemtuzumab | CAMMS223 | Phase II | Early RRMS | ↓ SAD (combined alemtuzumab arms=9%, IFN-β-1a = 26.2%) ↓ ARR (combined alemtuzumab arms = 0.1, IFN-β-1a = 0.36) |
| 6 month | ||||
| Single blind | ||||
| Double-dummy | ||||
| Randomized 1:1:1 12mg, 24mg or IFN-β-1a tiw | ||||
| CARE MS I | Phase III | Treatment naïve RRMS | ↓ ARR by 55% | |
| 2 year | ||||
| Rater-blinded | ||||
| Double-dummy | ||||
| Randomized 1:1 of 12mg | ||||
| IV X 5 days in year 1 plus 12mg | ||||
| IV X 3 days in year 2 or IFN-β-1a | ||||
| CARE MS II | Phase III | RRMS with ≥2 relapses within 2 years prior to enrollment with ≥ 1 relapse within 1 year prior to enrollment | ↓ ARR by 49% ↓ SAD by 42% |
|
| 2 year | ||||
| Rater-blinded | ||||
| Double-dummy | ||||
| Randomized 1:1 of 12mg | ||||
| IV x 5 days in year 1 plus | ||||
| 12mg x 3 days in year 2, or IFN-β-1a | ||||
| Daclizumab | CHOICE | Phase II | RRMS with active disease on IFN-β-1a | ↓ New or enlarged Gd+ lesions with daclizumab add-on (High dose add-on = 1.32, low dose add-on = 3.58, placebo = 4.75) |
| Daclizumab as add-on therapy to IFN-β-1a | ||||
| 6 month | ||||
| Double-blind | ||||
| Placebo-controlled | ||||
| Randomized 1:1:1 of 2mg/kg SQ q 2 weeks, 1mg/kg SQ q4 weeks or add-on placebo | ||||
| SELECT | Phase IIb | RRMS | ↓ ARR (low and high dose daclizumab) ↓ Cumulative number of new Gd+ lesions (high dose = 78% decrease, low dose = 69% decrease) |
|
| 1 year | ||||
| Double-blind, | ||||
| Placebo-controlled | ||||
| Randomized 1:1:1 of 150mg, 300mg, or placebo SQ q4 weeks | ||||
| DECIDE | Phase III | RRMS | Trial currently enrolling | |
| Double-blind | ||||
| Parallel-group | ||||
| Active control | ||||
| Randomized 1:1 of 150mg SQ q4 weeks or IFN-β-1a | ||||
| Ocrelizumab | Phase II | 96 week | RRMS, ≥ 2 relapses within past 3 years, ≥ 1 relapse within past 1 year, 6 T2 lesions on MRI within past year | Week 24: ↓ Gd+ lesions (low dose =89%, high dose = 96%) ↓ ARR (low dose = 80%, high dose = 73%) Week 96: ↓ Gd+ lesions by 99.8% for combined Ofatumumab arms |
| Double-blind | ||||
| Placebo-controlled | ||||
| Randomized 1:1:1:1 of 600mg IV on day 1 and 15 | ||||
| Ofatumumab | Phase II | 48 week | RRMS, ≥ 2 relapses in past 2 years or ≥ 1 relapse in past year or ≥ 1 relapse between previous 12–24 months and 1 Gd+ lesion on MRI | |
| Double-blind | ||||
| Placebo-controlled | ||||
| Randomized to 2:1 (Treatment vs. placebo) 100mg IV, 300mg IV, 700mg IV, or placebo with cross-over at 24 weeks | ||||
| Natalizumab | AFFIRM | Phase III | RRMS, ≥ 1 relapse within past 12 months | ↓ Sustained progression of disability by 42% over two years ↓ Rate of relapse at one year by 68% ↓ ARR (natalizumab = 0.24, Placebo = 0.75) ↓ T2 lesions (natalizumab = 1.9, placebo = 11) ↓ Gd+ lesions (natalizumab = 0.1, placebo = 1.2) |
| 2 year | ||||
| Placebo-controlled | ||||
| Double-blind | ||||
| Randomized 2:1 to 300mg IV q4 weeks or placebo | ||||
| GLANCE | Phase II | Relapsing MS on GA 12 months, 1 relapse in past 12 months | ↓ Mean rate of new active lesions (combination = 0.03, GA = 0.11) ↓ Mean number of new or enlarging T2 lesions (combination = 0.5 ± 1.1, IFN-β-1a = 1.3 ± 2.1) ↓ Mean cumulative number of new Gd + lesions (combination = 0.6 ± 1.8, IFN-β-1a = 2.3 ± 5.3) |
|
| 6 month | ||||
| Placebo-controlled | ||||
| Double-blind | ||||
| Randomized 1:1 Natalizumab 300mg IV q 4 weeks plus GA or placebo plus GA | ||||
| SENTINNEL | Phase III | RRMS on IFN-β-1a for ≥ 12 months, ≥ 1 relapse in past 12 months | ↓ ARR at 1 year (Combination = 0.34, IFN-β-1a = 0.75) ↓ Cumulative probability of sustained disease progression at year two (combination=23%, IFN-β-1a = 29%) ↓ New or enlarging T2 lesions (combination = 0.9, IFN-β-1a = 5.4)Gd+ lesions (combination = 0.1, IFN-β-1a = 0.9) |
|
| 2 year | ||||
| Placebo-controlled | ||||
| Double-blind | ||||
| Randomized 1:1 to Combination Natalizumab 300mg IV every 4 weeks = IFN-β-1a vs. IFN-β-1a monotherapy |