rpf>lement 1
`
`H ANNUAL MEETING PROGRAM
`
`Sawai (IPR2019-00789), Ex. 1014, p. 001
`
`

`

`Contents
`
`·
`
`Poster Sessions
`Neurogenctics Enhanced Vett ical Integration
`Poster Se sion
`Sunday, April 10, 2005
`Monday, April I I , 2005
`I. Tuesday morning, April 12, 2005
`II. Tuesday afternoon, April 12, 2005
`Ill. Wednesday morning, April 13, 2005
`JV. Wcdn<'sday afternoon, April 13, 2005
`V. Thmsday morning, April 14, 2005
`VI. Thursday afternoon, April 14, 2005
`
`Scientific Sessions
`Sunday, April 10, 2005
`I. Neuro-Ophthalmology/Neuro-Otology
`2.
`eurogenetics
`
`Monday, April 11, 2005
`3.
`euro-Oncology
`4. Sleep Disorders
`
`Tuesday, April 12, 2005
`5. Aging and Dementia: Mild Cognitive Impairment
`6. Multiple Sclerosis: Outcomes
`7. ~lovemenl Disorders: Dystonia
`8. Cerebrovascular Disease
`9. New Mutation ror Basilar-Type Migraine; CDH:
`Classification, Risk Factors, Prognosis
`10. Epilepsy: Basic Science and Genetics
`11. Behavioral eurology
`12. Multiple Sclerosis: Basic Science
`13. Clinical ALS
`I.J.
`•eurologic ~lanifestations of Systemic Disease
`15. Aging and Dementia: Treatment
`16. l\luluple Sclerosis: Clinical Trials I
`
`AS
`A18
`A29
`A73
`A160
`A207
`A292
`A341
`
`A1
`A3
`
`A25
`A26
`
`A126
`A127
`A129
`A130
`
`A1 32
`A134
`A136
`A138
`A140
`A142
`A144
`A146
`
`I 7. Movl'ment Disordl'rs: Gl'netics and Pathophysiology
`A147
`of Parkinsonism
`A149
`18. Stroke: Epidemiology I
`19. Acutl' and Prophylactic l\ligrarne Tlw rapy: Anatomical
`A 150
`and Physiologic Targ<'ls and Novel StralC'gres
`A 152
`20. Epilepsy:
`l'urormaging and F'unctional T<·sting
`A153
`21.
`Behavioral Neurology
`A155
`22.
`EEG and Clinical Neurophysiology
`A157
`23.
`A.LS Basic Science
`A1 58
`24. Inclusion Body Myositis
`
`Wednesday, April 13, 2005
`25. Aging and Dementia: Non Alzhp1mcr's Dis<'asc
`Dementia
`26. Multiple Sclerosis: Imaging
`27. Movement Disorders: G<'nelics, Pathophysiology arid
`Epidemiology
`28. Acute Stroke Therapy: Thrombolysis
`29. History of Neurology
`30. Epilepsy: Clinical Epil<'psy ancl New l"rontiNs
`31. Aging and Dementia: Epidemiology
`32. Multiple Sclerosis: Immunology I
`33. Stroke: Clinical Aspects
`34. Movement Disorders: Imaging
`35. Aging and Oemen1ia: Pathology
`36. ~lult iple Sclerosis: Cli111cal Tnals II
`37. Movement Disord<'rs: Surgical Treal 111cm
`38. Stroke: Epidemiology II
`39.
`euroepidemiology and Parkinson's Disem,e
`40.
`Epilepsy: Surgical Therapy and Other Treatment
`Issues
`Behavioral Neurology
`EMG and Clinical I europhysiology
`Cerebral I lemorrhage
`Muscle Disease and ~lyasthenia Gravis
`
`41.
`42.
`43.
`44.
`
`Thursday, April 14, 2005
`45. Aging and Demenlia: Imaging
`
`A257
`A259
`
`A261
`A263
`A264
`A266
`A267
`A269
`A271
`A273
`A275
`A276
`A279
`A280
`A282
`
`A283
`A285
`A286
`A288
`A289
`
`A389
`
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`Sawai (IPR2019-00789), Ex. 1014, p. 002
`
`

`

`S46.001
`1:30 PM
`A Double-Blind, Placebo-Controlled, Multicenter
`Study To Assess the Safety and Efficacy of AVP·
`923 (Dextromethorphan/Quinidine) in the
`Treatment of Pseudobulbar Affect in Patients
`with Multiple Sclerosis Hillel Panitch, Burlington, VT, Ro(cid:173)
`nald A. Thisted, Chicago, IL, Laura E. Pope, James E. Berg, San
`Diego, CA
`OBJECTIVE: The objective was to evaluate the safety, tolerance, a_nd
`eflicacy of A VP-923 (capsules containing dextromethorphan hydrobromide
`!DM; 30 mgJ and quinidine s ulfate IQ; 30 mg!), compared with placebo, for
`the treatment of pseudobulbar affect (PBA) in patients with multiple scle(cid:173)
`rosis (MS). BACKGROUND: PBA is associated with various neurological
`disorders and is characterized by uncontrollable episodes of lnughing
`and/or crying out-of-proportion to, or incongruent with, underlying mood. Q
`is included in the formulation as a CYP2D6 inhibitor to block the rapid
`first-pass metabolism of OM and increase its pharmacological potential.
`DESIGN/METHODS: MS patien ts at 22 community and unive rs ity based
`centers were randomized to receive AVP-923 (n =76) or placebo (n = 74)
`twice daily (ql2h) for 12 weeks. Each patient completed a diary recording
`daily the number of laughing and/or crying epsiodes, medication schedule,
`and adverse events (AEs). Patients returned to the clinic an Days 15, 29,
`57, and 85 for evaluation. PBA was assessed during the clinic visits using a
`validated self-assessment tool referred to as the CNS-LS. The study en(cid:173)
`rolled adult male and female patients with MS who scored .a: 13 on the
`CNS-LS. Safety measures were AEs, clinical chemistry, vital signs, physi(cid:173)
`cal examinations and ECGs. The primary efficacy analysis compared the
`change in CNS-LS score between the A VP-923 and placebo groups, where
`individual change was the difference between the baseline and the average
`of the Day 15, 29, 57 and 85 study visits. Secondnry endpoints included a
`comparison of the number of episodes of laughing and/or crying, a visual
`analog scale (VAS) score for overall quality of life, a VAS score for quality of
`relationships and a pain intensity rating scale score. RESULTS: Patients
`receiving A VP-923 had a clinically and statistically greater reduction in
`CNS-LS than those receiving placebo (p< 0.0001). All 4 secondary end(cid:173)
`points were also statistically significant in favor of A VP-923: number of
`laughing and crying episodes (p =0.0002); quality of life (p <0.0001), quality
`of relationships (p =0.0001); and pain reduction (p =0.027). Additional anal(cid:173)
`ysis revealed that nearly twice as many A VP-923 subjects as placebo sub(cid:173)
`jects responded to treatment (84% vs 49%; p< 0.0010), that the number of
`episodes per week was reduced 46% in the A VP-923 group compared to the
`placebo group and that t reatment effects were observed as early as the first
`week of treatment. The nature, frequency and intensity of AEs were within
`acceptable limits, and were similar between groups. Dizziness was ob(cid:173)
`served more frequently in the AVP-923 group (p=0.01). Eleven AVP-923
`patients (14%) and 8 placebo patients (11%) had AEs resulting in discontin(cid:173)
`uation. There were no clinically significant changes observed in other
`safety measures . CONCLUSIONS: AVP-923 was safe well-tolerated and
`highly effective in treating pseudobulbar affect in pati~nts with MS. '
`Supported by: Avanir Pharmaceuticals
`Disclo su re: Dr. Panitch hns received personal compensation for activities with: Berlex,
`Tcv~ Neuroscience, Serono, Pfizer'. Advanced B_iotherapy, Centocor, llex Oncology, G)y.
`commds, and Cenentech. Dr. Panit.ch has received personal compensation in an edito(cid:173)
`ria l capacity for 81oscicnce Communications for serving on an editorial board. Dr.
`Panit.ch has received compensation for serving on the Board of Directors of Advanced
`Biotherapy. Dr. Panitch has received financial s upport for research activities from
`Biogen-Idec, Teva Neuroscience, Scrono, Pfizer, Avanir, Gcncntcch, Bayer, and Bristol(cid:173)
`Mye~ Squibb. Dr. Thist..cd has received personal compensation for activities with:
`Avamr Pharmaceuticals for statistical consulting services and from Finnegan, Hender(cid:173)
`son, et al, _a la~\' firm . ~r. Pope has ~erved as an investigator ond holds stock options
`and/or options ~n Avan1r Pha ~mac~ut1cals .. Mr. Berg has served as an investigator and
`holds s tock options and/or options in Avnmr Phnrmnccuticals.
`
`S46.002
`1:45 PM
`
`Ginkgo Biloba Improves Cognitive Performance in
`Multiple Sclerosis Patients with Cognitive
`Dysfunction: A Pilot Study Bridget Bagert, Boston, MA,
`Jesus Lovera,. Barry Olien, Portland, OR, Kyle Smoot, Seattle, WA,
`Katherine Wild, Rachel Frank, Kristin Bogardus, Dennis Bour(cid:173)
`dette, Portland, OR
`OBJECT.IVE: To determine if. multiple sclerosis (MS) subjects with cogni(cid:173)
`tive 1mpa1rment treated with gmkgo b1loba (GB) improve their performance
`on a neuropsycholog,cal test battery as compared to placebo treated sub(cid:173)
`Jects. BACKGROUND: Cognitive dysfunction is a major cause of disability
`m MS, and presently there is no effective treatment. One agent that
`ha.ve _some benefit is GB, which many MS patients use despite a pauci;':,i;.
`e ,ustmg evidence to support such use. DESIGN/METHODS: This was a
`t wo-arm, P.arallel des ign, r_a?do?'ized, double-blind placebo-controlled, trial
`m MS patients with cogn1~1~e impairment. Subjects had to have de finite
`MS .and demonstrate cognitive drsfunction on the Paced Auditory Serial
`Add1t1on Test (PASAT) or the Cahforma Verbal Learning Test-II (CVL Tl!).
`SubJects who scored > 19 on t he Becks Depression Inventory (BDI) we re
`
`excluded. Eligible subjects also u nderwent the following tests: Stroopr _,
`Word Test; Controlled Oral Word Association Test; Symbol Digit ModaJi ~
`liot
`Tes t; adapted Useful Field of Vision Test. Subjects underwent th
`psychological test batteries over a five week period to minimize~~
`effects. The third test battery served as the baseline. Subjects w earning
`randomized to receive either GB (120 mg twice a day) or place~~ the,
`weeks. Platelet function analyses (PFA) were performed at baseli or II
`
`exit s ince GB has been reported to.impair P.latelet function. ANCO~;:
`
`used to compare the two groups wit h baseline performance in each f b,
`cognitiv~ tests, gender, EDSS, time since_ onset a.nd baseline BDI inc~~
`as covanates. For the PFA results at ex1.t, bas_ehne PFA results were th,
`only covariate mcluded. RESULTS: Th1rty-nme s ubJec.ts completed th,
`study, 20 received GB and 19 placebo. There were no s1gn1ficantdiO'ereou,
`between the groups on gender, age, education, type of MS, years .
`onset, or baseline performance on t he neuropsychological tests. There:""
`significant difference between t he groups at exit on the Stroop.;:.:
`(p=0.02). At baseline the means were 29.56 sec for t he placebo group "'1
`31.84 sec for GB. At exit the GB group improved to 24.63 sec while tb,
`placebo group was essentially unchanged at 30.22 sec. There were no sig.
`nificant differences between groups on other tests. There were no signifi.
`cant side-effects in eithe r group and no significant difference at exit ·
`PFA. The baseline PFA with epinephrine mean for placebo was 123.0;
`and for GB 120.5 sec and at exit 126.1 sec for the placebo group and 86.l
`sec for the GB group. CONCLUSIONS: This pilot trial suggests that GB
`may be effective in improving attention in MS patients with cogniti,,
`dysfunction. GB d id not alter platelet function or cause significant sid,.
`effects. Definitive investigation should be pursued.
`Su p por ted by: National Multiple Sclerosis Society grant #PP0921, tb,
`National Institutes of Health P50AT00066-0l, the Department of Vet,,.
`ans Affairs, a nd the Nancy Davis Center Without Walls. Gingko Bilobawa,
`provided by Thorne Research Inc.
`Disclosure: Ors. Bogert a nd Lovera have nothing to disclose. Dr. Oken has l'fflirtd
`financial s upport from NIH (NIA nnd NCCAM). Ors. Smoot nnd Wild have n•thinc•
`disclose. Ms. Frank and Bogardus have nothing to disclose. Dr. Bourdette has l'tCffll'd
`personal compensation for activities with: Biogen Idec, Teva Ncurosciences, Seronob!
`Berlex Laboratories for speaking engagements and consulting services.
`
`S46.003
`2:00PM
`
`An Open-Label, Prospective Study of Oral
`Fumaric Acid Therapy for the Treatment of
`Relapsing-Remitting M ultiple Sclerosis (RRMS) S.
`K. Schimrigk, N. Brune, K. Hellwig, M. Rieks, V. Hoffmann, D.
`Pohlau, H. Przunteh, Bochum, Germany
`OBJECTIVE: To evaluate the safety and efficacy of oral fumaric acid in
`patients with RRMS. BACKGROUND: Fuma ric acid is an effective and
`safe therapy for psoriasis. Since the inOammatory processes involved io
`multiple sclerosis (MS) are thought to be similar to those of psoria.<is,
`fumaric acid therapy may also be effective in t reating MS. DESIGN/
`METHODS: An exploratory, prospective, open-label study of oral fumaric
`acid esters was conducted in patients with RRMS. The study consisted of
`four phases, a 6-week baseline, an 18-week treatment at a target dose of
`720 mg per day, a 4-week washout, and a second 70-week treatment phas,
`at a target dose of 360 mg per day. All patients were t reated with oral
`fuma1ic acid ester therapy. The dose was slowly titrated up to the target
`dose over 9 weeks in the 1st treatment period. Patients started at the
`target dose in the second treatment phase. All patients had Gadolinium
`enhancing lesions on baseline Brain MRL Safety was assessed by physical
`and neurologic exams, blood chemistryn1ematology, electrocardiogram, and
`urinalysis. The primary eflicacy outcomes were the number and volume of
`gadolinium-enhancing (Gd +) lesions on seria l T l-weighted mngnetic res,,
`nance imaging (MRI) scans. Clinical outcomes included Expanded Disabil·
`ity Status Scale (EDSS) score, ambulation index (Al), and nine-hole P'i
`test (9-HPT). The effects of fumaric acid on intercellular cytokine profiles,
`T-cell apoptosis, and soluble adhesion molecule (slCAM-1) were also as·
`sessed. RES UL TS: Of 10 enrolled in the study, 3 patients discontinued
`during the first 3 weeks of treatment . Six of 7 patients initially expenenced
`mild to moderate gastrointestinal discomfort which decreased grnduallym
`all patients. All other s ide effects were gen;rally mild and transient. Fu·
`marrc acid therapy significantly reduced the number (p < 0.05) and volume
`(p <0.01) of Gd + les ions from baseline after 12 weeks of treatment. EDSS
`~cores, ~ . and 9-HPT re?'ai.ned stable or s lightly improved from. ba!elin,'
`mall patients. A highly s1gn1ficant increase in CD4+ cells producing inlf
`leukin OL)-10, IL-4, and TGF-beta was observed during treatment com·
`pared with baseline and post-study periods. A 50% increase in the rate .C
`apoptosis in T-helper (TH) cells was observed after 6 weeks of treatment
`and declined to baseline levels after an addition 6 weeks of treatment. No
`significant changes in intercellular T H I-type cytokine production was ob(cid:173)
`served while serum levels of s lCAM-1 were s ignificantly decreased. CONr
`CLUSIONS: Fumaric acid s ignificantly reduced the number and volume•
`Gd+ lesions over 70 weeks of treatme n t and all patients were clinically
`stable throughout the study. No serious adverse events were reported. Data
`on immunologic parameters suggest t hat fumaric acid causes a bystander
`k'
`·
`profile.
`supp e
`he
`r ss10~ pattern toward a predominantly TH2-type cyto i~e
`These findmgs suggest t hat further study of oral fumaric acid for t
`treatment of RRMS is warranted.
`S u pported b y: Presentation of this study supported by Biogen Idec, Inc.
`
`A892 NEUROLOGY 64 March 2005 (Suppl I)
`
`Sawai (IPR2019-00789), Ex. 1014, p. 003
`
`

`

`Disclosure:: Dr. Schimrigk hos ~ivcd po~on!l compe~sation for nctivilies wilh:
`8. en Idec and other phormn~ut1cal companies involved m t.he Lre~Lmenl or M.S. ~r.
`Sc~mrigk has received finane10J s upport from several pharmocuel1cal companies 1n(cid:173)
`\lOl;ed with the treotmcnt of MS hos . been provided for teat?ing activ!ti.e! al .the
`Bochum Univcrsily. Dr. Brune hos received personal compensation ror act1v1t.1es w1Lh:
`B' en Idec and other phormoccutical companies involved in the treatment of MS. Dr.
`8'0ine has received financial s upport. (tom several phormncuctical companies involved
`~ the treatment or MS hat been provided for teaching activities at. the Boe.hum
`~~i\lersity. Ors. Hellwig and Riek s have nothing to disclose. Dr. Hoffmann hos teceived
`nonal compensotion for activities with: Biogen Idec ond other phatmaceut.icol compn(cid:173)
`P!es involved in the treatmcnL or MS. Dr. Hoffmann hos received financial support rrom
`:;\lerol phormocu~ti.cal companies involved ~ ith .the treatment of MS has ~n provided
`ror leaching octiv1t1cs at the Dochum Univcts 1ty. Dr. Pohlou hos received personal
`compensation for activities wit h Biogen Idec ond other pharmaceutical companies in(cid:173)
`,•ol\led in the trentment or MS. Dr. Pohlou hos received financial support from several
`pharmocuctical companies involved with the treatment or MS hos been provided for
`teaching ect1vit1es ot the Bochum University, Dr. Przuntek hos_ received personal com(cid:173)
`pen.sation for oct1v1tics with: Biogen Idec :1nd other phormaceut1c:1l compon,cs involved
`10 the treatmen t or MS. Dr Przuntck has received financial support from scverol
`phermocuetical companies involved ~1th _the treatment of MS has been provided for
`teriching activities nt the Bochum Uni vers ity.
`
`546.004
`2:15 PM
`A Phase I Trial of CTLA41g Treatment in MS Samia
`J. Khoury, Vissia Viglietta, Guy Buckle, Dauid Hafler, Boston,
`MA, Kasia Bourcier, Bethesda, MD, Charles Guttmann, Michelle
`Bikowski, Boston, MA, James Rusche, Hal Landy, James Mc(cid:173)
`Nally, Karen Jauregui, Waltham, MA
`OBJECTIVE: To determine the safety of RG2077 in patients with multiple
`sclerosis. BACKGROUND: Multiple sclerosis (MS) is an autoimmune dis(cid:173)
`ease of the central nervous system initiated by autoreactive C04 + T cells,
`which recognize and respond to myelin antigens. T cell activation depends
`on signals delivered through the T cell receptor and co-stimulation via
`CD28-C0 80/CD86 interactions. CTLA4-lg has been used to block CD28-
`CD80/86 costimulation in several a nimal models of autoimmune disease,
`with improvement in disease manifestations. Previous studies using an·
`other CTLA4lg agent have shown clinical benefit in psoriasis and rheums·
`toid arthritis. RG2077 (Repligen) is a recombinant protein of CTLA4
`(cytolytic-T-lymphocyte associated antigen-4) fused to the heavy chain con·
`stant region of the human immunoglobulin of the JgG4 isotype. The gene
`sequence encoding the immunoglobulin port ion has been altered to remove
`the functional properties of binding the Fe receptor and fixation of comple(cid:173)
`ment. DESIGN/METHODS: We performed an open-label, dose escalation
`study of RG2077 in relapsing-remitting MS patients. Each subject received
`n single infusion of RG2077 in the one of the following dosage groups: 2.0
`mg/kg (n • 4), 10.0 mg/kg (n = 4), 20.0 mg/kg (n = 4) and 35.0 mg/kg (n =
`4). Safety assessments included blood studies, a MRI, a neurological exam(cid:173)
`ination and physical examination. Mechanistic studies were performed al
`baseline, I week, I month and 3 months post infusion. Safety data on the
`first 2 dose groups were presented at the AAN in 2004. The study was
`supported by the Immune Tolerance Network. RESULTS: We are cur(cid:173)
`rently dosing the 35.0 mg/kg cohort, and the last follow up visit is expected
`in March '05. No major adverse events have been observed to date. Immu·
`nologic/mechanistic studies have been performed a nd show evidence of
`biologic activity. The results of the safety data and analysis of the immuno·
`logic effects of the treatment on the whole study cohort will be presented.
`CONCLUSIONS: CTLA4Ig treatment appears to be safe for MS patients.
`Supported by: The Immune Tolerance Network
`Disdosurc: Dr Khoury hos received personal compens ation for activities with: Scrono,'
`Pfiicr fellowship program Or. Viglietta has nothing to disclose. Dr. Buckle hos received
`personal compensation for a ctivities with: Berlex, Biogen/Elon, Serono/Pfizcr, nnd Tevo
`phgormoceuticols. Dr HaOer has received personal compensation for activities with:
`Tcvo for consulting scrv1ce!J:. Dr. Bourc1e r hOJ nothing to disclose. Dr. Guttmann hos
`received personal compcns ntion for acttvities with: Teva Neuroscicnccs1 Serono, ond
`Bu,gen Ms Bikows k1 has nolhing to disclose. Dr Rusche has received personal compen(cid:173)
`sation for nct1v1t1cs with H:cphgen corporot1on Dr. Rusche hM received compenso_tion
`for serving on th e Boa.rd of Directors of Rcpligcn corporation. Dr. Londy hos received
`ptrsonal compensation for activ1ucs with : Rephgcn corporation. Dr. Lundy hos received
`compensauon for serving on the Board or Directors of Rephgen corporation. Dr. McNolly
`ha!I received personal compensation for activilics with: Repligen corporalion. Dr. Jnu (cid:173)
`regui ha.s rece1\'ed personal compensation for octivities with: Re pligen corporalion
`$46.005
`2:30 PM
`lmmunoablation Followed by Autologous Stem
`Cell Transplantation as a Treatment for
`Aggressive Multiple Sclerosis: 3 Year Follow-Up
`of the First 6 Patients Mark S. Freedman, Harold L. At(cid:173)
`kins, Guylaine Theoret, Ottawa, ON, Canada, and The Canadian
`MS BMT Study Group
`013.ffiCTIVE: To report on the progress of the Canadian MS bone ma_rrow
`transplant (BMT) study by providing clinical data on the first 6 patients
`reaching the final 3 year endpoint. BACKGROUND: We hypothesized that
`complete ablation of the immune system will halt any ongoing MS immune
`mediated damage to the CNS and that reconstitu ting an immune system
`derived from hematopoietic stem cells will not result in re-development of
`autoimmune disease. We also predicted that suppressing inflammation
`
`might facilitate endogenous repair mechanisms, or that repair comes di(cid:173)
`rectly from the transplanted stem cells that have the capacity to become
`CNS cells. The first six patients are now 3 years out from this procedure
`and this report deals with their clinical and functional outcomes. DESIGN/
`METHODS: The Canadian BMT t rial is a non-randomized phase II trial of
`immunoablation and autologous hematopoietic T cell-depicted s tem cell
`transplantation (ASCT) for MS patients deemed to have early aggressive
`disease a nd who have failed contemporary treatment. lmmunoablation was
`carried out using busulphan (16 mg/kg), cyclophosphamide (200 mg/kg) and
`rabbit ATG (5mg/kg). Patients were followed and assessed every 3 months
`by both 'treating' and 'blinded' evaluators. Clinical evaluations included the
`EOSS and MSFC functional scales as well as depression and quality of life
`measures. RESULTS: By the time of presentation most of these patients
`will have completed nearly 36 months of follow-up and their clinical data
`will be presented. One of these first six patients is a 'control' patient, who
`met the same rigid inclusion/exclusion criteria of the treated pa lien ts, but
`chose not to undergo the full procedure. This individual was followed in the
`same manner as the transplanted patients, but received only 'best medical
`care', which entailed the use of mitoxantrone. Thus far, no clinical attack
`has occurred in over 230 months of follow-up of 11 transplanted patients.
`Functional scales demonstrate either stability or improvement in a number
`of measures. In some cases, vision recovered substantially, while in othe rs
`there were marked improvements in pyramidaVcercbellar KFS or overall
`EOSS. In addition to reviewing EDSS and MSFC scoring, we will present
`the results of validated quality of life questionnaires com11leted prospec(cid:173)
`tively over the same time frame. MRI study results will be presented in a
`companion abstract, but similarly failed to detecl any new activity in any
`patient. CONCLUSIONS: Immunoablation and ASCT results in clinical
`stabilization or improvement in this very aggressive form of MS for up to 3
`years. Some patients have actually seen some improvement in terms of
`their motor and visual capabilities, raising the possibility thal the treat(cid:173)
`ment does more than simply stop ongoing disease activity.
`Supported by: Multiple Sclerosis Foundation of Canoda
`Dis clos ure: Or. Freedman hos received personal compensation for oct1v1t1cs with
`Berlex, Schcring, Serono, Teva, Biogen Idec, Bayer, 8 10MS, Bayhill Therapeutics, Ncu(cid:173)
`rocrine, Glycomind.s, Tnn.s1tion Therapeuucs, Pfizer Dr Freedman has received finan (cid:173)
`cinl support for Serono: clinical research project Glycominds clinical research proJect
`Serono: monthly journal club. Dr. Atkins ha.s nothing to disclose. Theorel and The
`Canadian MS BMT Study Group ha,•e nothing to disclose.
`
`546.006
`2:45 PM
`Evidence for Acute Brain "Pseudo-Atrophy" after
`Treating MS wit h lmmunoablation Followed by
`Autologous Stem Cell Transplantation Jacqueline T.
`Chen, Donald L. Collins, Montreal, QC, Canada, Mark S. Freed·
`man, Harold L. Atkins, Ottawa, ON, Canada, the Canadian MS
`BMT Study Group, Douglas L. Arnold, Montreal, QC, Canada
`OBJECTIVE: To assess the effect of stopping inflammation on the evolu·
`tion of brain atrophy in patients with multiple sclerosis (MS). BACK·
`GROUND: Brain atrophy is usually considered a biomarker of
`neurodegeneration and loss of brain tissue. However, fl uid shifts and other
`factors can acutely alter brain volume. Pseudo-atrophy due to the resolu(cid:173)
`tion of inflammatory edema has been proposed as a factor contributing to
`loss of brain volume after initiation of therapy in MS. To test this hypothe(cid:173)
`sis, we measured the rate of atrophy in patients with very aggressive,
`active MS before and after stopping inflammation with 1mmunoablation
`that was performed prior to autologous stem cell transpla_ntation (ASCT).
`DESIGN/METHODS: Brain MRI was performed at baseline (·2.5 mo and
`-0.6 mo) and post-immunoablation ( + 1 mo, +4 mo, +6 mo, +9 mo, + 12
`mo), in five patients wilh secondary-progressi~e MS. Quantifica~io_n of
`brain atrophy was performed on T l w MRI using SIENA. Gadohmum(cid:173)
`enhancing lesions were also quantified. RESULTS: At baseline, 4 of 5
`patients had gadolinium enhancing lesions (14:!:8 lesions/subject). Over a
`2-month interval prior to immunoablation, the rate of atrophy was small
`a nd heterogeneous within the group (mean:!:SO = - 0 .79:!:3.47 %/yr ,
`p=0.64). The rate of atrophy dramaticaHy in~reased over ~he subsequent 4
`months during which the patients received 1mmunoablat1ve dos?s of che(cid:173)
`motherapy and ASCT (8.65:!:2.60 %/yr (p=0.003)). In some pat1.ents, the
`rote of atrophy stabilized by l month post-transplant. In other patients, the
`rate of atrophy stabilized after 4- 6 months. CONCLUSIONS: lmmunoab(cid:173)
`lot ion followed by ASCT was associated with an acute increase in the rate
`of atrophy. The rate of atrophy (approximately 3% over 4 months) was
`larger than what one would normally expect due to !oss of tissue, even in
`this aggressive group of MS pat(en~ . These p~ehminary data, therefore,
`support the hypothesis that stopping inflammation m MS can be associated
`with "pseudo-atrophy".
`.
`.
`.
`.
`Supported by: The Multiple Sclerosis Sc1ent1fic Research Foundation . .
`Disclosure: Ms. Chen has received financial support. for The Multiple Sclerosis &1en(cid:173)
`tific Rcscorch Foundation. Dr. Collins hos nothing to discl~. Or. Freedman h~ re(cid:173)
`ceived personal compensation for acti\lilics wilh: Bc~lex, Schenn.g, Serono, ~e.vo, Biogen
`Idec, Boyer, BioMS, Bayhill Therapeutics, Neurocnne, Glycommd.s, Trans 1t1on .Thero·
`pcutics, Pfizer. Or. Freedman hos received fino?cial support from Se~no: chmcnl re(cid:173)
`search project Glycominds: clinical reseorc~ proJecl Serono: monthly Journal clu~. Dr.
`Atkins hu nothing to disc.lose, the Canadian MS BM! Study G.~u.p ha~ n?thmg to
`disclose. Dr. Arnold hos received personal compensot1on r~r act1v1t1~s with. Acol'dn,
`Biogen Idec, Berlex. Gencntech, Immune Response Corporation, :;thermg, Scrono, and
`Teva.
`
`A393 NEUROLOGY 64 March 2005 (Suppl I)
`
`Sawai (IPR2019-00789), Ex. 1014, p. 004
`
`