Treating primary-progressive multiple sclerosis: potential of ocrelizumab and review of B-cell therapies

Figures & data

Table 1 Completed ocrelizumab in MS trials to date, with details on trial design and significant results

Trial	Phase	Design	Population	Sample Size	Ocrelizumab Dosage	Duration	Outcomes	Adverse Events
NCT00676715^Citation57	II	Randomized, double-blind, placebo-controlled	RRMS	220	600 mg (given at 300 mg 2W apart) first cycle, then 600 mg second cycle 2,000 mg (given as 1,000 mg 2W apart) first cycle, then 1,000 mg second cycle	48 weeks	• 80% and 73% reduction in ARR for 600 mg and 2,000 mg, respectively • 89% and 96% reduction in # of GEL for 600 mg and 2,000 mg, respectively	• 47%–66% experienced AE • 2% in 600 mg group experienced serious AE vs 4%–6% in 2,000 mg group • 35% and 44% experienced IRR in 600 mg and 2,000 mg, respectively • No opportunistic infections
OPERA I/II^Citation108	III	Randomized, double-blind, IFNβ-1a controlled	RRMS	821 + 835	600 mg IV Q24W	96 weeks	• 46% and 47% reduction in ARR • 43% and 37% risk reduction to CDP at 12 and 24 weeks • 94% and 95% reduction in # of GEL • 77% and 83% reduction in # of new/enlarging T2 lesions	• 83.3% experienced AE • 6.9% serious AE • IRR most common AE (34.3%) • No significant difference to IFN
ORATORIO^Citation110	III	Randomized, double-blind, placebo-controlled	PPMS	732	600 mg IV Q24W (given as 300 mg 2W apart)	120 weeks	• 24% and 25% risk reduction of CDP for 12 and 24 weeks, respectively • 3.4% decrease in T2 lesion volume • 17.5% reduced rate of brain atrophy	• 20.4% serious AE • IRR most common AE (39.9%) • No significant difference to placebo

Abbreviations: AE, adverse event; IV, intravenous; ARR, annualized relapse rate; RRMS, relapsing–remitting multiple sclerosis; GEL, gadolinium-enhancing lesions; CDP, confirmed disability progression; PPMS, primary-progressive multiple sclerosis; Q24W, every 24 weeks; 2W, 2 weeks; IRR, infusion-related reaction.

Table 2 Currently available and investigational B-cell therapies for MS

Drug	Antigen target, epitope	Trials completed	Trials ongoing	FDA approval
Ocrelizumab	CD20, binds to large loop ^170ANPS^173 core epitope, P168 and P170 assist in binding	Phase II in RRMS Phase III in RRMS and PPMS		On fast-track evaluation for PPMS
Rituximab	CD20, binds to large loop ^170ANPS^173 core epitope, ^182YCYSI^186 assists in binding	Phase I and II in RRMS Phase II/III in PPMS	Phase I in PPMS
Ofatumumab	CD20, binds to large loop FLKMESLNFIRAHTP core epitope and regions in small loop	Phase II in RRMS	Phase III in RRMS
Ublituximab	CD20		Phase II in RRMS
Alemtuzumab	CD52	Phase II and III RRMS Phase II in SPMS and PPMS		Approved for RRMS
Atacicept	BAFF, APRIL	Phase II in RRMS
Tabalumab	BAFF	Phase II RRMS
Belimumab	BAFF

Abbreviations: FDA, US Food and Drug Administration; PPMS, primary-progressive multiple sclerosis; RRMS, relapsing–remitting multiple sclerosis; SPMS, secondary-progressive multiple sclerosis.

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