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even when you think one might exist," Dr. Riley says. "And so the expense of running a study that 's long enough ... is astronomical." B CELLS TO THE FORE The South San Francisco biotechnology company Genentech, a member of the Roche Group, may have at least a partial answer to the treatment puzzle posed by PPMS, in the form of ocrelizumab. "In people with R R MS a nd PPMS, areas where the brain is infl amed and nerve cells are losing their insulation and support often contain a high number of CD20-positive B cells," says Peter Chin, MD, Principal Medical Director, Global Neuroscience Development at the Roche Group. "Ocrelizumab is designed to selectively target CD20-positive B cells. [These] cells are a specifi c type of immune cell thought to be a key contribu- tor to myelin and axonal nerve damage, which can result in disability in people with MS. Based on preclinical studies, ocrelizumab binds to CD20 cell surface proteins expressed only on certain B cells, and not on stem cells or plasma cells, and therefore important functions of the immune system may be preserved." I n l at e 2 01 5 , G enent ech relea sed f i n d i n g s f r o m t h r e e r a n d o m i z e d , double-blind Phase 3 studies of ocreli- zumab. Two of the studies — OPER A¬I a nd OPER A¬ II — focused on R R MS. T he st ud ies t est ed t he ef f ica c y a nd sa fet y of ocrelizumab compa red with t h at of i nt er feron bet a-1 a , a w idely prescr ibed d r ug for relapsi ng for ms of M S . C omp a r e d w it h i nt e r fe r on bet a-1a , ocreli z u mab reduced st udy participants' annua lized relapse rate by nea rly 50 percent during the two-yea r study period and delayed confirmed dis- abilit y prog ression at both the 12- a nd 24-week ma rkers by about 40¬percent. The drug 's sa fet y was simila r to inter- feron beta-1a's. The third study, OR ATOR IO, mea- sured ocrelizumab's eff icacy and safety against placebo in 732 individua ls with PPMS . T he st udy wa s event- d r iven rat her t ha n const ra i ned by a preset duration; it concluded on ly when a l l participants had received either ocreli- zumab or placebo for 120 weeks, a nd t he st udy reached a tota l con f ir med d i s a bi l it y pr og r e s sion b ench m a rk . F i nd i n g s of ocrel i z u m a b's ef f ica c y compa red with placebo included: + A 25 percent reduction in risk of pro- gression of clinical disability sustained for at least 24 weeks + A 29 percent reduction in time to com- plete the Timed 25-Foot Walk test over 120 weeks + A 17.5 percent reduction in whole-brain volume loss over 120 weeks Ocrelizumab also reduced the volume of hyperintense T2 lesions by 3.4 percent over 120 weeks; placebo increased the volume of these lesions by 7.4 percent. Ocrelizumab's safety profi le was similar to placebo's. " For decades, tr ia l a f ter tr ia l ha s failed to show the benefi t of any medi- cine for people w it h PPMS," Xav ier Mont a lba n , M D, Ph D, Ch a i r of t he Scientif ic Steering Committee of the OR ATOR IO st udy a nd P rofessor of Neurolog y a nd Neuroimmunolog y at Vall d'Hebron University Hospital and Research Institute in Barcelona, Spain, said in a news release from Genentech. "Now, for the fi rst time, we have a positive Phase 3 study result for people with this debilitating form of the disease." During the fi rst half of 2016, Genentech pla nned to seek reg ulator y approva l for ocrelizumab to treat both R R MS and PPMS. CAUTIOUS OPTIMISM Dr. Riley, who was not involved with the ocrelizumab studies, thinks clinicians and patients can be hopeful about the fi ndings, as long as they have a realistic outlook. "It 's ver y appea ling to have a drug that has data in both [RRMS and PPMS] because you could potentially hedge your bets a bit [as a clinician]," Dr. Riley says. "You could say, 'I think this is probably PPMS, but maybe that was a relapse back then,' and so ... we have an agent that potentially works for both. Knowing that this B-cell-directed therapy has eœ cacy in each form of the disease ... is sort of opening new doors for us thinking about the role of B cells. "I am enthusiastic about [the fi ndings], but I don't think [ocrelizumab] is going to work for ever yone," she continues. "None of our medicines does. People who have had severe impairment are unlikely to see reversal of their impair- ment. It's just important to have realistic expectations."¬■ SPECIAL CLINICAL SECTION: NEUROLOGY M D N E W S . C O M /// M D N E W S L O N G I S L A N D ■ 2 016 2 1

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