Table 2.

Current mAb therapies under development for multiple sclerosis

Name	mAb type	Target	Mechanism			Company	Development phase
Natalizumab	IgG4κ	Alpha4 integrin	Blocking lymphocyte migration CNS			Biogen Idec Elan	FDA/EMA approved
Studies	Clinicaltrials.gov identifier	Patient numbers	MS type	Comparator	Duration	Benefit/Risk
AFFIRM	NCT00027300	942	RMS	Placebo	2 years	Clear reduction ARR, disease-free status and MRI activity
SENTINEL	NCT00030966	1171	RMS	NAT + IFNb1a i.m. NAT + placebo	2 years	Hypersensitivity reactions 2 PML cases detected
Daclizumab	IgG1	Alpha-chain CD25	Blocking IL-2 binding to T cells Expansion NK CD56bright regulatory cells			Biogen Idec Facet Biotech	Phase 2 ongoing Phase 3 started
Studies	Clinicaltrials.gov identifier	Patient numbers	MS type	Comparator	Duration	Benefit/Risk
CHOICE	NCT00109161	230	RMS	DAC + IFNb1a Placebo + IFNb1a	6 months	Reduction in MRI activity
SELECT	NCT00390221	600 pln	RMS	Placebo	12 months	Slight increase in infection rates
DECIDE	NCT01064401	1500 pln	RMS	IFNb1a i.m.	2–3 years
Alemtuzumab	IgG1κ	CD52	Immune cell depletion Post-reconstitution increase in regulatory T cell population			Genzyme Bayer-Schering	Phase 2 completed Phase 3 planning
Studies	Clinicaltrials.gov identifier	Patient numbers	MS type	Comparator	Duration	Benefit/Risk
CAMMS223	NCT00050778	344	RMS*	IFNb1a s.c.	2 years	Very significant reduction in ARR and MRI activity. Reversal in EDSS progression
CARE MS I	NCT00530348	581 pln	RMS*	IFNb1a s.c.	2 years	Trial prematurely stopped: 6 cases of ITP (1 fatal), thyroid disease
CARE MS II	NCT00548405	840 pln	RMS	IFNb1a s.c.	2 years
Rituximab	IgG1κ	CD20	B cell depletion Downstream effects on immune system			Genentech	Phase 2 completed
Studies	Clinicaltrials.gov identifier	Patient numbers	MS type	Comparator	Duration	Benefit/Risk
HERMES	NCT00097188	104	RMS	Placebo	48 weeks	Very significant reduction in MRI activity, reduction in ARR
OLYMPUS	NCT00087529	439	PPMS	Placebo	96 weeks	Trend for reduction in EDSS; subgroup analysis positive in younger patients with active MRI
						No significant safety issues in MS trials; PML cases have been reported in cancer and rheumatological diseases with RTX
Ocrelizumab	IgG1κ	CD20	B cell depletion Downstream effects on immune system			Roche Genentech	Phase 2 ongoing
Studies	Clinicaltrials.gov identifier	Patient numbers	MS type	Comparator	Duration	Benefit/Risk
Phase 2	NCT00676715	250 pln	RMS	Placebo IFNb1a i.m.	96 weeks	Results pending

^*Early active RMS: Disease onset <5 years, >2 relapses last 2 years, EDSS 0–3. ARR, annualized relapse rate; DAC, daclizumab; EDSS, Expanded Disability Status Scale; EMA, European Medicines Agency; FDA, United States Food and Drug Administration; IFN, interferon; i.m., intramuscular; MRI, magnetic resonance imaging; MS, multiple sclerosis; NAT, natalizumab; PPMS, primary progressive MS; Pln, planned; RMS, relapsing MS; RTX, rituximab; s.c., subcutaneous; PML, progressive multifocal leukoencephalopathy; ITP, immune thrombocytopenic purpura.