Table 4.
Efficacy of New and Emerging Oral Therapies.
| Therapy | Pivotal Trials | Design | Patients | Key Endpoints |
|---|---|---|---|---|
| Fingolimod | TRANSFORMS | 1 year | RRMS | ↓ ARR (0.5mg = 0.16, 1.25mg = 0.2, IFN = 0.33) ↓ New or enlarged T2 lesions ( high and low dose fingolimod arms) No difference in 3-month disability progression |
| Phase III | ||||
| Double-blind | ||||
| Double dummy | ||||
| Randomized 1:1:1 of 0.5mg, 1.25mg, or qwk IM IFN beta-1a | ||||
| FREEDOMS | 2 year | RRMS | ↓ ARR (0.5mg = 0.18, 1.25mg = 0.16, placebo = 0.4) Absence of 3-month disability progression (0.5mg = 82.3%, 1.25mg = 83.4%, placebo 75.9%) ↓ Number of Gd+ lesions (0.5mg = 0.2, 1.25mg = 0.2, placebo = 1.1) ↓ Number of new/enlarged T2 lesions (0.5mg = 2.5, 1.25mg = 2.5, placebo = 9.8) ↓ Volume of T1-hypointense lesions (0.5mg = 8.8, 1.25mg = 12.2, Placebo = 50.7) ↓ Brain atrophy (0.5mg = −0.37, 1.25mg = −0.42, placebo = 0.81) |
|
| Phase III | ||||
| Double-blind | ||||
| Randomized 1:1:1 or 0.5mg, 1.25mg, or placebo | ||||
| Teriflunomide | TEMSO | 2 year | RRMS, SPMS, PPMS | ↓ ARR (7mg = 31.2%, 14mg = 31.5%) ↓ Disability progression in 14mg group ↓ Decreased T2 lesion volume (7mg = 1.31, 14mg = 0.72, placebo = 2.21) ↓ Decreased Gd+ lesions (7mg = 0.57, 14mg = 0.26, Placebo = 1.33) ↓ Unique active lesions (7mg = 1.29, 14mg=0.75, Placebo = 2.46) ↓ Volume of T1 hypointense lesions in 14mg No difference in brain atrophy among groups |
| Phase III | ||||
| Double-blind | ||||
| Randomized 1:1:1 of 7mg, 14mg, or placebo | ||||
| TENERE | 2 year | No difference in risk of treatment failure No difference in ARR (7mg = 0.410, 14mg = 0.259, IFN = 0.216) |
||
| Phase III | ||||
| Rater-blinded | ||||
| Randomized 1:1:1 of 7mg, 14mg, or tiw IFN-β-1a | ||||
| BG-12 | DEFINE | 2 year | ↓ Risk of relapse (bid = 49%, tid = 50%) ↓ ARR (bid = 53%, tid = 48%) ↓ Risk of disability progression (bid=38%, tid=34%) |
|
| Phase III | ||||
| Double-blind | ||||
| Randomized 1:1:1 bid, tid, or placebo | ||||
| CONFIRM | 2 year | RRMS | ↓ARR (bid=44%, tid = 51%, GA = 29%) ↓New/enlarging T2 lesions (bid = 71%, tid = 73%, GA = 54%) ↓ New T1 hypointense lesions (bid=57%, tid=65%, GA = 41%) ↓ Proportion of patientsrelapsing (bid=34%, tid = 45%, GA = 29%) No difference in disability progression among groups |
|
| Phase III | ||||
| Double-blind | ||||
| Randomized 1:1:1:1 bid, tid, GA, or placebo | ||||
| Laquinimod | ALLEGRO | 2 year | RRMS | ARR ↓23% ↓ New/enlarging T2 lesions ↓ New T1 hypointense lesions ↓ Brain atrophy Disability progression ↓36% Brain atrophy ↓32.8% Rate of severe relapses (↓27% |
| Phase III | ||||
| Randomized 1:1 of 0.6mg or placebo | ||||
| BRAVO | 2 year | RRMS | Adjusted ARR (0.6mg = 0.29, placebo = 0.37, IFN-β-1a = 0.27) ↓ Risk of disability progression Brain atrophy ↓27.5% |
|
| Phase III | ||||
| Double-blind | ||||
| Randomized 1:1:1 of 0.6mg, placebo, or qwk IM IFN-β-1a |