Sfety of Ocrelizumb in Multiple Sclerosis: Updted Anlysis in Ptients With Relpsing nd Primry Progressive Multiple Sclerosis SL Huser, L Kppos, X Montlbn, H Koendgen, C Chognot, C Li, C Mrcillt, A Prdhn, D Wormser, JS Wolinsky Phse II (NCT676715); OPERA I (NCT1247324); OPERA II (NCT1412333); ORATORIO (NCT119457); VELOCE (NCT2545868); CHORDS (NCT2637856); CASTING (NCT286114); OBOE (NCT2688985) Presented t the 7th Americn Acdemy of Neurology (AAN) Annul Meeting; April 21 27, 218; Los Angeles, CA, USA Pltform presenttion number S36.1 OCR/32218/83d http://bit.ly/husers1
Disclosures SL Huser serves on the bord of trustees for Neuron nd on scientific dvisory bords for Annexon, Bionure nd Symbiotix nd hs received trvel reimbursement nd writing ssistnce from F. Hoffmnn-L Roche Ltd for CD2-relted meetings nd presenttions. L Kppos s institution, the University Hospitl Bsel, hs received reserch support nd pyments tht were used exclusively for reserch support for Prof. Kppos s ctivities s principl investigtor nd member or chir of plnning nd steering committees or dvisory bords for trils sponsored by Actelion, Addex, Almirll, Byer HelthCre Phrmceuticls, CLC Behring, F. Hoffmnn-L Roche Ltd nd Genentech, Inc., GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Phrm, Novrtis, Octphrm, Ono Phrmceuticl, Pfizer, Receptos, Snofi, Snther, Siemens, Tev, UCB nd XenoPort; hs received license fees for Neurosttus products; nd hs received reserch grnts from the Europen Union, Ginni Rubtto Foundtion, Novrtis Reserch Foundtion, Roche Reserch Foundtion, Swiss Multiple Sclerosis Society nd Swiss Ntionl Reserch Foundtion. H Koendgen is n employee nd shreholder of F. Hoffmnn-L Roche Ltd. C Chognot is n employee of F. Hoffmnn-L Roche Ltd. C Li is n employee of F. Hoffmnn-L Roche Ltd. C Mrcillt is n employee of F. Hoffmnn-L Roche Ltd. A Prdhn is n employee of Genentech, Inc. D Wormser is n employee nd shreholder of F. Hoffmnn-L Roche Ltd. JS Wolinsky hs served on dvisory bords nd dt monitoring or steering committees, hs held consulting greements or hs received speker honorri from AbbVie, Alkermes, Biogen, Bionest, Clene Nnomedicine, EMD Serono, F. Hoffmnn-L Roche Ltd, Forwrd Phrm, Genentech, Inc., MedDy Phrmceuticls, Novrtis, Snofi Genzyme, Tked, Tev, nd hs received roylties for monoclonl ntibodies outlicensed to Chemicon Interntionl through UTHelth. X Montlbn hs received speker honorri nd trvel expense reimbursement for prticiption in scientific meetings, been steering committee member of clinicl trils or served on dvisory bords of clinicl trils for Actelion, Almirll, Byer, Biogen, F. Hoffmnn-L Roche Ltd, Genzyme, Merck, Novrtis, Octphrm, Receptos, Snofi, Tev nd Trophos. This study ws sponsored by F. Hoffmnn-L Roche Ltd, Bsel, Switzerlnd. Writing nd editoril ssistnce for this presenttion ws provided by Articulte Science, UK, nd funded by F. Hoffmnn-L Roche Ltd, Bsel, Switzerlnd. http://bit.ly/husers1 2
Proportion of ptients hving confirmed disbility progression Cumultive probbility of event (%) Adjusted ARR Totl number of new or enlrging 12 lesions per MRI scn Efficcy bckground.5.4.3.2.1 3 25 2 15 1 5.276 p<.1.141 OPERA OLE: ARR 1 Ptients receiving IFN β-1 44μg during the DBP Ptients switching from IFN β-1 to OCR n=829 n=827 n=713 n=765 n=623 n=72 n=594 n=665 Week 48 (DBP Yer 1) Week 48 96 (DBP Yer 2) Week 96 144 (Yer 3/OLE Yer 1) Week 144 192 (Yer 4/OLE Yer 2) IFN β-1/ocr OCR/OCR DBP: HR=.6; p=.3.23 p<.1.126 p<.1 p=.7.98.15 OPERA OLE: CDP (24-week) 1 Strt of OLE =4.31 (1.27, 7.35); p=.5 Ptients continuing OCR 6 mg tretment p=.3 =4.85 (1.52, 8.18); p=.4 p=.99.82.82 Immture dt =5.44 (1.97, 8.91); p=.2 =4.84 (1.16, 8.52); p=.1 =4.36 (.51, 8.22); p=.27 Bseline 24 48 72 96 12 144 168 192 216 24 264 Time to onset of confirmed disbility progression (weeks) No. of ptients t risk IFN β-1/ocr 6 mg 829 785 747 75 677 644 623 62 588 535 523 51 58 494 489 473 471 297 286 127 12 19 15 OCR 6 mg/ocr 6 mg 827 797 772 748 731 717 74 691 678 644 631 614 61 583 581 561 56 376 364 156 151 3 24 2.5 2. 1.5 1..5. p<.1 ARR, nnulized relpse rte; CDP, confirmed disbility progression; CI, confidence intervl; DBP, double-blind period; ECP, extended control period; HR, hzrd rtio; IFN, interferon; OLE, open-lbel extension; OCR, ocrelizumb; PBO, plcebo. 1. Huser SL, et l. AAN 218; Poster 366; 2. Arnold DL, et l. AAN 218; Pltform presenttion 2; 3. Wolinsky JS, et l. ECTRIMS 217; Poster 1234. 1 8 6 4 2 1.593 OPERA OLE: New/enlrging T2 lesions 2 Ptients receiving IFN β-1 44μg during the DBP Ptients switching from IFN β-1 to OCR.761 p<.1 1.1.6 p<.1 2.159.52 p<.1.333 n=747 n=772 n=694 n=754 n=65 n=72 n=58 n=646 n=536 n=599 Weeks 24 Weeks 24 48 Weeks 48 96 Yer 1 Yer 2 Weeks 96 142 Yer 3 (OLE Yer 1) ORATORIO ECP: CDP (24-week) 3 PBO (N=244) OCR 6 mg (N=488) HR=.7 (95% CI.55.9); p=.5 Ptients continuing OCR 6 mg tretment.87.63.8 Weeks 142 19 Yer ~4 (OLE Yer 2) Bseline 12 24 36 48 6 72 84 96 18 12 132 144 156 168 18 192 24 216 228 24 Time (weeks) No. of ptients t risk PBO 244 234 214 22 193 183 176 166 157 148 139 129 119 85 65 48 36 21 7 2 OCR 6 mg 487 465 454 437 421 397 384 367 349 33 313 35 296 267 183 155 94 77 25 2 2 http://bit.ly/husers1 3
Bckground nd objectives In the Phse III trils, the most common dverse events (AEs) ssocited with ocrelizumb (OCR) included infusion-relted rections, nsophryngitis, upper respirtory trct infections, hedche nd urinry trct infections 1,2 Objectives: To report ongoing sfety evlutions from OCR clinicl trils nd ssocited open-lbel extension (OLE) periods up to 217 To provide n updte on the incidence rtes of mlignncies in the OCR clinicl tril progrm, in the context of dt from epidemiologicl dt sources (MS registries) nd the generl popultion (Ntionl Cncer Institute Surveillnce, Epidemiology, nd End Results dtbse) To report post-mrketing dt for ftlities nd progressive multifocl leukoencephlopthy (PML) up to Mrch 218 AEs, dverse events; MS, multiple sclerosis; OCR, ocrelizumb; OLE, open-lbel extension; PML, progressive multifocl leukoencephlopthy. 1. Huser SL, et l. N Engl J Med 217;376:221 234; 2. Montlbn X, et l. N Engl J Med 217;376:29 22. http://bit.ly/husers1 5
Methods Sfety nlyses re bsed on integrted dt for ll ptients who received OCR in the following clinicl trils, s of 217 (OCR ll-exposure popultion): The Phse II nd Phse III MS clinicl trils nd ssocited OLE periods (Ph II/Ph III nd OLEs popultion) The primry nlysis ws bsed on the clinicl cut-off dtes of the individul studies VELOCE: Effect of OCR on immune responses in ptients with RMS CHORDS/CASTING: Study of OCR in ptients with RRMS with suboptiml response to disese-modifying tretment (USA/Europe) OBOE b : Mechnism of ction of OCR nd B-cell biology in ptients with RMS or PPMS AEs re reported s rtes per 1 ptient yers (PY) The number of post-mrketing ptients exposed to OCR is bsed on estimted totl number of vils sold, s well s US clims dt Phse II, Jnury 215; OPERA I, April 215; OPERA II, My 215; ORATORIO, July 215; b The clinicl cut-off dte used for OBOE ws June 217. AEs, dverse events; MS, multiple sclerosis; OCR, ocrelizumb; OLE, open-lbel extension; PPMS, primry progressive multiple sclerosis; PY, ptient yers; RMS, relpsing multiple sclerosis; RRMS, relpsing-remitting multiple sclerosis. http://bit.ly/husers1 6
Tretment exposure Chrcteristic OCR ll-exposure popultion (N=3,778) Totl ptient yers 9,474 Number of doses, n (%) b,c 1 2 3 4 5 6 7 8 9 1 Men (SD) number of doses Medin number of doses Totl cumultive dose, mg Men (SD) Medin Rnge Number of ptients exposed 3,778 (1) 3,271 (86.6) 2,373 (62.8) 2,78 (55.) 1,791 (47.4) 1,738 (46.) 1,542 (4.8) 1,3 (34.4) 1,121 (29.7) 1,62 (28.1) 5.7 (4.2) 4. 3,47 (2,485) 2,4 9 11,8 Dt cut-off: 217. Doses were dministered every 6 months. Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217); dt from ptients who were originlly rndomized to comprtor (IFN β-1 or plcebo) re included fter the switch to open-lbel OCR tretment; b If ptient received ny infusion in one dose, it ws counted s one dose; c More thn four doses equls more thn 2 yers exposure, nd more thn eight doses equls more thn 4 yers exposure. IFN, interferon; OCR, ocrelizumb; OLE, open-lbel extension; SD, stndrd devition. http://bit.ly/husers1 7
Sfety profile observed with ocrelizumb Event OPERA (pooled) controlled tretment period ORATORIO controlled tretment period Ph II/Ph III nd OLEs popultion b OCR ll-exposure popultion c IFN β-1 rte per OCR rte per Plcebo rte per OCR rte per Sept 217 rte per Sept 217 rte per 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d,e 1 PY (95% CI) d,e Any dverse events 296 (287 35) 29 (281 299) 259 (247 271) 252 (244 26) 22 (217 223) 243 (24 246) Adverse events leding to study tretment discontinution 3.93 (2.96 5.12) 2.35 (1.63 3.28) 1.1 (.47 2.16) 1.25 (.76 1.92) 1.18 (.97 1.44) 1.9 (.89 1.32) Infections nd infesttions f,g 67.8 (63.5 72.2) 84.5 (79.9 89.4) 72.5 (66.5 79.) 7.8 (66.8 75.) 7.3 (68.6 72.1) 73.1 (71.4 74.8) Urinry trct infection Nsophryngitis Upper respirtory trct infection Bronchitis Influenz Injury, poisoning nd procedurl complictions f Infusion-relted rections Nervous system disorders h Hedche Musculoskeletl nd connective tissue disorders f Bck pin Arthrlgi Pin in extremity Generl disorders nd dministrtion site conditions f Ftigue Psychitric disorders f Depression 9.7 (8.1 11.4) 8.3 (6.9 9.9) 9.4 (7.8 11.1) 2.2 (1.5 3.1) 3.3 (2.4 4.4) 17.1 (15. 19.4) 7.9 (6.5 9.5) 34.8 (31.8 38.) 12.4 (1.6 14.4) 25. (22.5 27.8) 3.1 (2.2 4.1) 3.9 (3. 5.1) 2.9 (2.1 4.) 51.3 (47.6 55.2) 5.7 (4.5 7.1) 14.2 (12.3 16.3) 4.2 (3.2 5.4) 11.6 (9.9 13.5) 13. (11.2 15.) 13.3 (11.5 15.3) 3.5 (2.6 4.6) 3.1 (2.3 4.2) 45.9 (42.4 49.5) 34.9 (31.9 38.1) 31.6 (28.8 34.7) 9.5 (8. 11.3) 24.3 (21.8 27.) 4.1 (3.1 5.3) 3.5 (2.6 4.6) 3.7 (2.7 4.8) 17.3 (15.2 19.5) 5.4 (4.3 6.7) 14.4 (12.5 16.5) 4.9 (3.8 6.2) 17.8 (14.9 21.2) 17.7 (14.8 21.) 2.9 (1.8 4.4) 2.9 (1.8 4.4) 3.4 (2.2 5.1) 36.3 (32.1 41.) 2.3 (17.2 23.8) 22.4 (19.1 26.1) 6.7 (5. 8.9) 31.7 (27.7 36.) 7.4 (5.6 9.7) 4.3 (2.9 6.) 4.7 (3.2 6.5) 15.6 (12.9 18.8) 4.4 (3. 6.2) 11.8 (9.4 14.6) 5.1 (3.6 7.) 15.1 (13.2 17.1) 12.8 (11.1 14.6) 5.2 (4.2 6.5) 2.6 (1.9 3.5) 4.6 (3.6 5.7) 43.5 (4.3 46.8) 31. (28.3 33.9) 22.6 (2.3 25.1) 6.3 (5.1 7.6) 22.8 (2.5 25.3) 4.8 (3.8 6.) 3. (2.2 4.) 2.4 (1.7 3.2) 12.7 (11. 14.6) 1.9 (1.3 2.7) 7.7 (6.4 9.2) 2.4 (1.7 3.3) 12.7 (12. 13.5) 1.2 (1. 1.5) 9.4 (8.8 1.1) 3.1 (2.8 3.5) 2.9 (2.6 3.3) 31.5 (3.3 32.7) 21.5 (2.5 22.4) 2.6 (19.7 21.6) 5.2 (4.8 5.7) 19.3 (18.4 2.3) 3.4 (3. 3.8) 2.8 (2.4 3.1) 2.3 (2. 2.6) 1.7 (1. 11.4) 3. (2.7 3.4) 7.8 (7.3 8.5) 2.7 (2.4 3.1) 12.8 (12.1 13.5) 1.2 (1. 1.4) 9.6 (9. 1.2) 3.1 (2.8 3.5) 3.1 (2.7 3.5) 38.8 (37.6 4.1) 28.4 (27.3 29.5) 24.2 (23.2 25.2) 7. (6.5 7.6) 2.9 (2. 21.9) 3.7 (3.3 4.1) 3. (2.7 3.4) 2.7 (2.4 3.1) 12.8 (12.1 13.5) 3.7 (3.3 4.1) 8.6 (8. 9.2) 2.8 (2.4 3.1) Mlignncies i,j.14 (.2.52).28 (.8.71).27 (.3.99).93 (.52 1.54).51 (.37.68).48 (.35.64) Serious dverse events Serious infections k Number of confirmed serious OIs 6.29 (5.5 7.75) 1.79 (1.16 2.64) 5.39 (4.26 6.72).83 (.43 1.45) 12.7 (9.68 14.87) 3.2 (1.89 4.57) 1.15 (8.65 11.83) 2.74 (1.99 3.68) 7.42 (6.85 8.1) 2.1 (1.73 2.33) 1 7.29 (6.76 7.86) 1.96 (1.69 2.27) 1 Ftlities.14 (.2.52).7 (.38).41 (.8 1.2).25 (.7.64).18 (.11.3).17 (.1.27) Includes ptients who received plcebo or IFN β-1 during the controlled tretment period of the Phse III studies; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; dt from ptients who were originlly rndomized to comprtor (IFN β-1 or plcebo) re included fter the switch to open-lbel OCR tretment; c Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217); d Multiple occurrences of the sme dverse event (except for mlignncies) in one ptient re counted multiple times; e Rte per 1 PY (95% CI) s of 217; f Includes events occurring in 5% of ptients; g Includes events flling into the MedDRA versions 18., 18.1, 19.1 nd 2. SOC Infections nd Infesttions; h Non-serious MS relpses re not considered s n dverse event. If n dverse event reported term ws coded to the preferred term Multiple Sclerosis Relpse, regrdless of seriousness, it ws considered s n dverse event. When the MS relpse resulted in hospitliztion for ny reson other thn the routine tretment of the relpse, or when the hospitliztion ws prolonged, the relpse ws considered s serious dverse event; i Includes non-melnom skin cncer s per MedDRA version SMQ Mlignnt Tumours; j Reported s incidence rte per 1 PY of first mlignncy; k Serious infections re defined using dverse events flling into the MedDRA SOC Infections nd Infesttions, nd using Is the event non-serious or serious? from the dverse event cse report form. CI, confidence intervl; IFN, interferon; MedDRA, Medicl Dictionry for Regultory Activities; MS, multiple sclerosis; OCR, ocrelizumb; OIs, opportunistic infections; OLE, open-lbel extension; PY, ptient yers; SMQ, stndrdized MedDRA query; SOC, system orgn clss. http://bit.ly/husers1 9
Sfety profile observed with ocrelizumb Event OPERA (pooled) controlled tretment period ORATORIO controlled tretment period Ph II/Ph III nd OLEs popultion b Includes ptients who received plcebo or IFN β-1 during the controlled tretment period of the Phse III studies; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; dt from ptients who were originlly rndomized to comprtor (IFN β-1 or plcebo) re included fter the switch to open-lbel OCR tretment; c Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217); d Multiple occurrences of the sme dverse event (except for mlignncies) in one ptient re counted multiple times; e Rte per 1 PY (95% CI) s of 217; f Includes events occurring in 5% of ptients; g Includes events flling into the MedDRA versions 18., 18.1, 19.1 nd 2. SOC Infections nd Infesttions; h Non-serious MS relpses re not considered s n dverse event. If n dverse event reported term ws coded to the preferred term Multiple Sclerosis Relpse, regrdless of seriousness, it ws considered s n dverse event. When the MS relpse resulted in hospitliztion for ny reson other thn the routine tretment of the relpse, or when the hospitliztion ws prolonged, the relpse ws considered s serious dverse event; i Includes non-melnom skin cncer s per MedDRA version SMQ Mlignnt Tumours; j Reported s incidence rte per 1 PY of first mlignncy; k Serious infections re defined using dverse events flling into the MedDRA SOC Infections nd Infesttions, nd using Is the event non-serious or serious? from the dverse event cse report form. CI, confidence intervl; IFN, interferon; MedDRA, Medicl Dictionry for Regultory Activities; MS, multiple sclerosis; OCR, ocrelizumb; OIs, opportunistic infections; OLE, open-lbel extension; PY, ptient yers; SMQ, stndrdized MedDRA query; SOC, system orgn clss. OCR ll-exposure popultion c IFN β-1 rte per OCR rte per Plcebo rte per OCR rte per Sept 217 rte per Sept 217 rte per 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d,e 1 PY (95% CI) d,e Any dverse events 296 (287 35) 29 (281 299) 259 (247 271) 252 (244 26) 22 (217 223) 243 (24 246) Adverse events leding to study tretment discontinution 3.93 (2.96 5.12) 2.35 (1.63 3.28) 1.1 (.47 2.16) 1.25 (.76 1.92) 1.18 (.97 1.44) 1.9 (.89 1.32) Infections nd infesttions f,g 67.8 (63.5 72.2) 84.5 (79.9 89.4) 72.5 (66.5 79.) 7.8 (66.8 75.) 7.3 (68.6 72.1) 73.1 (71.4 74.8) Urinry trct infection Nsophryngitis Upper respirtory trct infection Bronchitis Influenz Injury, poisoning nd procedurl complictions f Infusion-relted rections Nervous system disorders h Hedche Musculoskeletl nd connective tissue disorders f Bck pin Arthrlgi Pin in extremity Generl disorders nd dministrtion site conditions f Ftigue Psychitric disorders f Depression 9.7 (8.1 11.4) 8.3 (6.9 9.9) 9.4 (7.8 11.1) 2.2 (1.5 3.1) 3.3 (2.4 4.4) 17.1 (15. 19.4) 7.9 (6.5 9.5) 34.8 (31.8 38.) 12.4 (1.6 14.4) 25. (22.5 27.8) 3.1 (2.2 4.1) 3.9 (3. 5.1) 2.9 (2.1 4.) 51.3 (47.6 55.2) 5.7 (4.5 7.1) 14.2 (12.3 16.3) 4.2 (3.2 5.4) 11.6 (9.9 13.5) 13. (11.2 15.) 13.3 (11.5 15.3) 3.5 (2.6 4.6) 3.1 (2.3 4.2) 45.9 (42.4 49.5) 34.9 (31.9 38.1) 31.6 (28.8 34.7) 9.5 (8. 11.3) 24.3 (21.8 27.) 4.1 (3.1 5.3) 3.5 (2.6 4.6) 3.7 (2.7 4.8) 17.3 (15.2 19.5) 5.4 (4.3 6.7) 14.4 (12.5 16.5) 4.9 (3.8 6.2) 17.8 (14.9 21.2) 17.7 (14.8 21.) 2.9 (1.8 4.4) 2.9 (1.8 4.4) 3.4 (2.2 5.1) 36.3 (32.1 41.) 2.3 (17.2 23.8) 22.4 (19.1 26.1) 6.7 (5. 8.9) 31.7 (27.7 36.) 7.4 (5.6 9.7) 4.3 (2.9 6.) 4.7 (3.2 6.5) 15.6 (12.9 18.8) 4.4 (3. 6.2) 11.8 (9.4 14.6) 5.1 (3.6 7.) 15.1 (13.2 17.1) 12.8 (11.1 14.6) 5.2 (4.2 6.5) 2.6 (1.9 3.5) 4.6 (3.6 5.7) 43.5 (4.3 46.8) 31. (28.3 33.9) 22.6 (2.3 25.1) 6.3 (5.1 7.6) 22.8 (2.5 25.3) 4.8 (3.8 6.) 3. (2.2 4.) 2.4 (1.7 3.2) 12.7 (11. 14.6) 1.9 (1.3 2.7) 7.7 (6.4 9.2) 2.4 (1.7 3.3) 12.7 (12. 13.5) 1.2 (1. 1.5) 9.4 (8.8 1.1) 3.1 (2.8 3.5) 2.9 (2.6 3.3) 31.5 (3.3 32.7) 21.5 (2.5 22.4) 2.6 (19.7 21.6) 5.2 (4.8 5.7) 19.3 (18.4 2.3) 3.4 (3. 3.8) 2.8 (2.4 3.1) 2.3 (2. 2.6) 1.7 (1. 11.4) 3. (2.7 3.4) 7.8 (7.3 8.5) 2.7 (2.4 3.1) 12.8 (12.1 13.5) 1.2 (1. 1.4) 9.6 (9. 1.2) 3.1 (2.8 3.5) 3.1 (2.7 3.5) 38.8 (37.6 4.1) 28.4 (27.3 29.5) 24.2 (23.2 25.2) 7. (6.5 7.6) 2.9 (2. 21.9) 3.7 (3.3 4.1) 3. (2.7 3.4) 2.7 (2.4 3.1) 12.8 (12.1 13.5) 3.7 (3.3 4.1) 8.6 (8. 9.2) 2.8 (2.4 3.1) Mlignncies i,j.14 (.2.52).28 (.8.71).27 (.3.99).93 (.52 1.54).51 (.37.68).48 (.35.64) Serious dverse events Serious infections k Number of confirmed serious OIs 6.29 (5.5 7.75) 1.79 (1.16 2.64) 5.39 (4.26 6.72).83 (.43 1.45) 12.7 (9.68 14.87) 3.2 (1.89 4.57) 1.15 (8.65 11.83) 2.74 (1.99 3.68) 7.42 (6.85 8.1) 2.1 (1.73 2.33) 1 7.29 (6.76 7.86) 1.96 (1.69 2.27) 1 Ftlities.14 (.2.52).7 (.38).41 (.8 1.2).25 (.7.64).18 (.11.3).17 (.1.27) http://bit.ly/husers1 1
Sfety profile observed with ocrelizumb Event OPERA (pooled) controlled tretment period ORATORIO controlled tretment period Ph II/Ph III nd OLEs popultion b Includes ptients who received plcebo or IFN β-1 during the controlled tretment period of the Phse III studies; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; dt from ptients who were originlly rndomized to comprtor (IFN β-1 or plcebo) re included fter the switch to open-lbel OCR tretment; c Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217); d Multiple occurrences of the sme dverse event (except for mlignncies) in one ptient re counted multiple times; e Rte per 1 PY (95% CI) s of 217; f Includes events occurring in 5% of ptients; g Includes events flling into the MedDRA versions 18., 18.1, 19.1 nd 2. SOC Infections nd Infesttions; h Non-serious MS relpses re not considered s n dverse event. If n dverse event reported term ws coded to the preferred term Multiple Sclerosis Relpse, regrdless of seriousness, it ws considered s n dverse event. When the MS relpse resulted in hospitliztion for ny reson other thn the routine tretment of the relpse, or when the hospitliztion ws prolonged, the relpse ws considered s serious dverse event; i Includes non-melnom skin cncer s per MedDRA version SMQ Mlignnt Tumours; j Reported s incidence rte per 1 PY of first mlignncy; k Serious infections re defined using dverse events flling into the MedDRA SOC Infections nd Infesttions, nd using Is the event non-serious or serious? from the dverse event cse report form. CI, confidence intervl; IFN, interferon; MedDRA, Medicl Dictionry for Regultory Activities; MS, multiple sclerosis; OCR, ocrelizumb; OIs, opportunistic infections; OLE, open-lbel extension; PY, ptient yers; SMQ, stndrdized MedDRA query; SOC, system orgn clss. OCR ll-exposure popultion c IFN β-1 rte per OCR rte per Plcebo rte per OCR rte per Sept 217 rte per Sept 217 rte per 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d,e 1 PY (95% CI) d,e Any dverse events 296 (287 35) 29 (281 299) 259 (247 271) 252 (244 26) 22 (217 223) 243 (24 246) Adverse events leding to study tretment discontinution 3.93 (2.96 5.12) 2.35 (1.63 3.28) 1.1 (.47 2.16) 1.25 (.76 1.92) 1.18 (.97 1.44) 1.9 (.89 1.32) Infections nd infesttions f,g 67.8 (63.5 72.2) 84.5 (79.9 89.4) 72.5 (66.5 79.) 7.8 (66.8 75.) 7.3 (68.6 72.1) 73.1 (71.4 74.8) Urinry trct infection Nsophryngitis Upper respirtory trct infection Bronchitis Influenz Injury, poisoning nd procedurl complictions f Infusion-relted rections Nervous system disorders h Hedche Musculoskeletl nd connective tissue disorders f Bck pin Arthrlgi Pin in extremity Generl disorders nd dministrtion site conditions f Ftigue Psychitric disorders f Depression 9.7 (8.1 11.4) 8.3 (6.9 9.9) 9.4 (7.8 11.1) 2.2 (1.5 3.1) 3.3 (2.4 4.4) 17.1 (15. 19.4) 7.9 (6.5 9.5) 34.8 (31.8 38.) 12.4 (1.6 14.4) 25. (22.5 27.8) 3.1 (2.2 4.1) 3.9 (3. 5.1) 2.9 (2.1 4.) 51.3 (47.6 55.2) 5.7 (4.5 7.1) 14.2 (12.3 16.3) 4.2 (3.2 5.4) 11.6 (9.9 13.5) 13. (11.2 15.) 13.3 (11.5 15.3) 3.5 (2.6 4.6) 3.1 (2.3 4.2) 45.9 (42.4 49.5) 34.9 (31.9 38.1) 31.6 (28.8 34.7) 9.5 (8. 11.3) 24.3 (21.8 27.) 4.1 (3.1 5.3) 3.5 (2.6 4.6) 3.7 (2.7 4.8) 17.3 (15.2 19.5) 5.4 (4.3 6.7) 14.4 (12.5 16.5) 4.9 (3.8 6.2) 17.8 (14.9 21.2) 17.7 (14.8 21.) 2.9 (1.8 4.4) 2.9 (1.8 4.4) 3.4 (2.2 5.1) 36.3 (32.1 41.) 2.3 (17.2 23.8) 22.4 (19.1 26.1) 6.7 (5. 8.9) 31.7 (27.7 36.) 7.4 (5.6 9.7) 4.3 (2.9 6.) 4.7 (3.2 6.5) 15.6 (12.9 18.8) 4.4 (3. 6.2) 11.8 (9.4 14.6) 5.1 (3.6 7.) 15.1 (13.2 17.1) 12.8 (11.1 14.6) 5.2 (4.2 6.5) 2.6 (1.9 3.5) 4.6 (3.6 5.7) 43.5 (4.3 46.8) 31. (28.3 33.9) 22.6 (2.3 25.1) 6.3 (5.1 7.6) 22.8 (2.5 25.3) 4.8 (3.8 6.) 3. (2.2 4.) 2.4 (1.7 3.2) 12.7 (11. 14.6) 1.9 (1.3 2.7) 7.7 (6.4 9.2) 2.4 (1.7 3.3) 12.7 (12. 13.5) 1.2 (1. 1.5) 9.4 (8.8 1.1) 3.1 (2.8 3.5) 2.9 (2.6 3.3) 31.5 (3.3 32.7) 21.5 (2.5 22.4) 2.6 (19.7 21.6) 5.2 (4.8 5.7) 19.3 (18.4 2.3) 3.4 (3. 3.8) 2.8 (2.4 3.1) 2.3 (2. 2.6) 1.7 (1. 11.4) 3. (2.7 3.4) 7.8 (7.3 8.5) 2.7 (2.4 3.1) 12.8 (12.1 13.5) 1.2 (1. 1.4) 9.6 (9. 1.2) 3.1 (2.8 3.5) 3.1 (2.7 3.5) 38.8 (37.6 4.1) 28.4 (27.3 29.5) 24.2 (23.2 25.2) 7. (6.5 7.6) 2.9 (2. 21.9) 3.7 (3.3 4.1) 3. (2.7 3.4) 2.7 (2.4 3.1) 12.8 (12.1 13.5) 3.7 (3.3 4.1) 8.6 (8. 9.2) 2.8 (2.4 3.1) Mlignncies i,j.14 (.2.52).28 (.8.71).27 (.3.99).93 (.52 1.54).51 (.37.68).48 (.35.64) Serious dverse events Serious infections k Number of confirmed serious OIs 6.29 (5.5 7.75) 1.79 (1.16 2.64) 5.39 (4.26 6.72).83 (.43 1.45) 12.7 (9.68 14.87) 3.2 (1.89 4.57) 1.15 (8.65 11.83) 2.74 (1.99 3.68) 7.42 (6.85 8.1) 2.1 (1.73 2.33) 1 7.29 (6.76 7.86) 1.96 (1.69 2.27) 1 Ftlities.14 (.2.52).7 (.38).41 (.8 1.2).25 (.7.64).18 (.11.3).17 (.1.27) http://bit.ly/husers1 11
Sfety profile observed with ocrelizumb Event OPERA (pooled) controlled tretment period ORATORIO controlled tretment period Ph II/Ph III nd OLEs popultion b OCR ll-exposure popultion c IFN β-1 rte per OCR rte per Plcebo rte per OCR rte per Sept 217 rte per Sept 217 rte per 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d 1 PY (95% CI) d,e 1 PY (95% CI) d,e Any dverse events 296 (287 35) 29 (281 299) 259 (247 271) 252 (244 26) 22 (217 223) 243 (24 246) Adverse events leding to study tretment discontinution 3.93 (2.96 5.12) 2.35 (1.63 3.28) 1.1 (.47 2.16) 1.25 (.76 1.92) 1.18 (.97 1.44) 1.9 (.89 1.32) Infections nd infesttions f,g 67.8 (63.5 72.2) 84.5 (79.9 89.4) 72.5 (66.5 79.) 7.8 (66.8 75.) 7.3 (68.6 72.1) 73.1 (71.4 74.8) Urinry trct infection Nsophryngitis Upper respirtory trct infection Bronchitis Influenz Injury, poisoning nd procedurl complictions f Infusion-relted rections Nervous system disorders h Hedche Musculoskeletl nd connective tissue disorders f Bck pin Arthrlgi Pin in extremity Generl disorders nd dministrtion site conditions f Ftigue Psychitric disorders f Depression 9.7 (8.1 11.4) 8.3 (6.9 9.9) 9.4 (7.8 11.1) 2.2 (1.5 3.1) 3.3 (2.4 4.4) 17.1 (15. 19.4) 7.9 (6.5 9.5) 34.8 (31.8 38.) 12.4 (1.6 14.4) 25. (22.5 27.8) 3.1 (2.2 4.1) 3.9 (3. 5.1) 2.9 (2.1 4.) 51.3 (47.6 55.2) 5.7 (4.5 7.1) 14.2 (12.3 16.3) 4.2 (3.2 5.4) 11.6 (9.9 13.5) 13. (11.2 15.) 13.3 (11.5 15.3) 3.5 (2.6 4.6) 3.1 (2.3 4.2) 45.9 (42.4 49.5) 34.9 (31.9 38.1) 31.6 (28.8 34.7) 9.5 (8. 11.3) 24.3 (21.8 27.) 4.1 (3.1 5.3) 3.5 (2.6 4.6) 3.7 (2.7 4.8) 17.3 (15.2 19.5) 5.4 (4.3 6.7) 14.4 (12.5 16.5) 4.9 (3.8 6.2) 17.8 (14.9 21.2) 17.7 (14.8 21.) 2.9 (1.8 4.4) 2.9 (1.8 4.4) 3.4 (2.2 5.1) 36.3 (32.1 41.) 2.3 (17.2 23.8) 22.4 (19.1 26.1) 6.7 (5. 8.9) 31.7 (27.7 36.) 7.4 (5.6 9.7) 4.3 (2.9 6.) 4.7 (3.2 6.5) 15.6 (12.9 18.8) 4.4 (3. 6.2) 11.8 (9.4 14.6) 5.1 (3.6 7.) 15.1 (13.2 17.1) 12.8 (11.1 14.6) 5.2 (4.2 6.5) 2.6 (1.9 3.5) 4.6 (3.6 5.7) 43.5 (4.3 46.8) 31. (28.3 33.9) 22.6 (2.3 25.1) 6.3 (5.1 7.6) 22.8 (2.5 25.3) 4.8 (3.8 6.) 3. (2.2 4.) 2.4 (1.7 3.2) 12.7 (11. 14.6) 1.9 (1.3 2.7) 7.7 (6.4 9.2) 2.4 (1.7 3.3) 12.7 (12. 13.5) 1.2 (1. 1.5) 9.4 (8.8 1.1) 3.1 (2.8 3.5) 2.9 (2.6 3.3) 31.5 (3.3 32.7) 21.5 (2.5 22.4) 2.6 (19.7 21.6) 5.2 (4.8 5.7) 19.3 (18.4 2.3) 3.4 (3. 3.8) 2.8 (2.4 3.1) 2.3 (2. 2.6) 1.7 (1. 11.4) 3. (2.7 3.4) 7.8 (7.3 8.5) 2.7 (2.4 3.1) 12.8 (12.1 13.5) 1.2 (1. 1.4) 9.6 (9. 1.2) 3.1 (2.8 3.5) 3.1 (2.7 3.5) 38.8 (37.6 4.1) 28.4 (27.3 29.5) 24.2 (23.2 25.2) 7. (6.5 7.6) 2.9 (2. 21.9) 3.7 (3.3 4.1) 3. (2.7 3.4) 2.7 (2.4 3.1) 12.8 (12.1 13.5) 3.7 (3.3 4.1) 8.6 (8. 9.2) 2.8 (2.4 3.1) Mlignncies i,j.14 (.2.52).28 (.8.71).27 (.3.99).93 (.52 1.54).51 (.37.68).48 (.35.64) Serious dverse events Serious infections k Number of confirmed serious OIs 6.29 (5.5 7.75) 1.79 (1.16 2.64) 5.39 (4.26 6.72).83 (.43 1.45) 12.7 (9.68 14.87) 3.2 (1.89 4.57) 1.15 (8.65 11.83) 2.74 (1.99 3.68) 7.42 (6.85 8.1) 2.1 (1.73 2.33) 1 7.29 (6.76 7.86) 1.96 (1.69 2.27) 1 Ftlities.14 (.2.52).7 (.38).41 (.8 1.2).25 (.7.64).18 (.11.3).17 (.1.27) Includes ptients who received plcebo or IFN β-1 during the controlled tretment period of the Phse III studies; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; dt from ptients who were originlly rndomized to comprtor (IFN β-1 or plcebo) re included fter the switch to open-lbel OCR tretment; c Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217); d Multiple occurrences of the sme dverse event (except for mlignncies) in one ptient re counted multiple times; e Rte per 1 PY (95% CI) s of 217; f Includes events occurring in 5% of ptients; g Includes events flling into the MedDRA versions 18., 18.1, 19.1 nd 2. SOC Infections nd Infesttions; h Non-serious MS relpses re not considered s n dverse event. If n dverse event reported term ws coded to the preferred term Multiple Sclerosis Relpse, regrdless of seriousness, it ws considered s n dverse event. When the MS relpse resulted in hospitliztion for ny reson other thn the routine tretment of the relpse, or when the hospitliztion ws prolonged, the relpse ws considered s serious dverse event; i Includes non-melnom skin cncer s per MedDRA version SMQ Mlignnt Tumours; j Reported s incidence rte per 1 PY of first mlignncy; k Serious infections re defined using dverse events flling into the MedDRA SOC Infections nd Infesttions, nd using Is the event non-serious or serious? from the dverse event cse report form. CI, confidence intervl; IFN, interferon; MedDRA, Medicl Dictionry for Regultory Activities; MS, multiple sclerosis; OCR, ocrelizumb; OIs, opportunistic infections; OLE, open-lbel extension; PY, ptient yers; SMQ, stndrdized MedDRA query; SOC, system orgn clss. http://bit.ly/husers1 12
Rte Rte per 1 ptient yers of serious infections during the Phse III studies PPMS exposure (PY): 631 OCR; 235 PBO 547 OCR; 217 PBO 43 OCR; 186 PBO 42 OCR; 85 PBO 333 OCR 113 OCR RMS exposure (PY): 1,423 OCR; 793 IFN β-1 1,359 OCR; 66 IFN β-1 1,156 OCR 749 OCR 473 OCR 66 OCR 12 11 1 9 8 7 6 5 4 3 2 1 Yer 1 Yer 2 Yer 3 Yer 4 Yer 5 Yer 6 RMS OCR RMS IFN β 1 PPMS OCR PPMS PBO Exposure to OCR nd comprtor (IFN β-1 or plcebo) in the Phse III pooled RMS nd PPMS popultions in totl PY. The exposure in Yer 5 nd Yer 6 (plcebo-treted ptients) ws too limited for ny meningful interprettion, thus these dt re not included in the plot. Investigtor text for dverse events ws encoded using MedDRA versions 18.1 nd 19.1. Multiple occurrences of the sme dverse event in one ptient re counted multiple times. Serious infections re defined using dverse events flling into the MedDRA SOC Infections nd Infesttions, nd using Is the event non-serious or serious? from the dverse event cse report form. 95% CIs were clculted using n exct method bsed on the Poisson distribution. CI, confidence intervl; IFN, interferon; MedDRA, Medicl Dictionry for Regultory Activities; OCR, ocrelizumb; PBO, plcebo; PPMS, primry progressive multiple sclerosis; PY, ptient yers; RMS, relpsing multiple sclerosis; SOC, system orgn clss. http://bit.ly/husers1 13
Crude incidence rte Crude incidence rte per 1 ptient yers of ll mlignncies over time compred with the Dnish MS registry 1. Ph II/Ph III nd OLEs popultion OCR ll-exposure popultion.8.43 (.26.66).44 (.29.65).4 (.26.59).45 (.31.64).45 (.32.63).48 (.35.64).6.2 (.5.5) Dnish Dnish.4.2 PBO+IFN β 1. Primry nlysis cut-off dte Jnury June Februry 216 216 216 217 217 b The incidence rte of first mlignncy (number of first mlignncy events per 1 PY) ws clculted. Dnish MS registry:.67 (.63.71). Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217). IFN, interferon; MS, multiple sclerosis; OCR, ocrelizumb; OLE, open-lbel extension; PBO, plcebo; PY, ptient yers. http://bit.ly/husers1 15
Crude incidence rte Crude incidence rte per 1 ptient yers of ll mlignncies over time compred with the Dnish MS registry 1. Ph II/Ph III nd OLEs popultion OCR ll-exposure popultion.8.43 (.26.66).44 (.29.65).4 (.26.59).45 (.31.64).45 (.32.63).48 (.35.64).6.2 (.5.5) Dnish.4.2 PBO+IFN β 1. Primry nlysis cut-off dte Jnury June Februry 216 216 216 217 217 b The incidence rte of first mlignncy (number of first mlignncy events per 1 PY) ws clculted. Dnish MS registry:.67 (.63.71). Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217). IFN, interferon; MS, multiple sclerosis; OCR, ocrelizumb; OLE, open-lbel extension; PBO, plcebo; PY, ptient yers. http://bit.ly/husers1 16
Age- nd sex-stndrdized incidence rte per 1 ptient yers of ll mlignncies over time compred with SEER dtbse Stndrdized incidence rte 1..8.6.4.2..29 (.16.57) Primry nlysis cut-off dte b.26 (.15.49) Ph II/Ph III nd OLEs popultion.24 (.14.43).24 (.14.42).24 (.15.41) SEER.25 (.16.39) Jnury June Februry 216 b 216 b 216 b 217 b 217 c SEER The incidence rte of first mlignncy (number of first mlignncy events per 1 PY) ws clculted. SEER:.27 (.27.27). NMSC is not reported in SEER; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; c Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217). NMSC, non-melnom skin cncer; OCR, ocrelizumb; OLE, open-lbel extension; PY, ptient yers; SEER, Surveillnce, Epidemiology, nd End Results. http://bit.ly/husers1 17
Age- nd sex-stndrdized incidence rte per 1 ptient yers of ll mlignncies over time compred with SEER dtbse Stndrdized incidence rte 1..8.6.4.2..29 (.16.57) Primry nlysis cut-off dte b.26 (.15.49) Ph II/Ph III nd OLEs popultion.24 (.14.43).24 (.14.42).24 (.15.41) OCR ll-exposure popultion.25 (.16.39) Jnury June Februry 216 b 216 b 216 b 217 b 217 c SEER The incidence rte of first mlignncy (number of first mlignncy events per 1 PY) ws clculted. SEER:.27 (.27.27). NMSC is not reported in SEER; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; c Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217). NMSC, non-melnom skin cncer; OCR, ocrelizumb; OLE, open-lbel extension; PY, ptient yers; SEER, Surveillnce, Epidemiology, nd End Results. http://bit.ly/husers1 18
Crude incidence rte Crude incidence rte per 1 ptient yers of femle brest cncer over time compred with three MS registries (Dnish, Swedish nd Cndin) 1. Ph II/Ph III nd OLEs popultion OCR ll-exposure popultion.8.6.4.2.26 (.11.54) Swedish (.29).23 (.1.46).23 (.11.44).22 (.1.41).19 (.9.37) Dnish.21 (.11.37) Dnish. Primry nlysis cut-off dte PBO+IFN β 1 Cndin Cndin Jnury June Februry 216 216 216 217 217 b The incidence rte of first mlignncy (number of first mlignncy events per 1 PY) ws clculted. Dnish MS registry:.21 (.18.23). Cndin British Columbi MS registry:.14 (.11.16). Swedish MS registry:.2 (.18.22). Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217). IFN, interferon; MS, multiple sclerosis; OCR, ocrelizumb; OLE, open-lbel extension; PBO, plcebo; PY, ptient yers. http://bit.ly/husers1 19
Crude incidence rte Crude incidence rte per 1 ptient yers of femle brest cncer over time compred with three MS registries (Dnish, Swedish nd Cndin) 1. Ph II/Ph III nd OLEs popultion OCR ll-exposure popultion.8.6.4.2.26 (.11.54) Swedish (.29).23 (.1.46).23 (.11.44).22 (.1.41).19 (.9.37).21 (.11.37) Dnish. Primry nlysis cut-off dte PBO+IFN β 1 Cndin Jnury June Februry 216 216 216 217 217 b The incidence rte of first mlignncy (number of first mlignncy events per 1 PY) ws clculted. Dnish MS registry:.21 (.18.23). Cndin British Columbi MS registry:.14 (.11.16). Swedish MS registry:.2 (.18.22). Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217). IFN, interferon; MS, multiple sclerosis; OCR, ocrelizumb; OLE, open-lbel extension; PBO, plcebo; PY, ptient yers. http://bit.ly/husers1 2
Stndrdized incidence rte Age-stndrdized incidence rte per 1 ptient yers of femle brest cncer over time compred with SEER dtbse 1. Ph II/Ph III nd OLEs popultion.8.6.28 (.1.67).24 (.1.54).23 (.1.5).21 (.9.47).19 (.8.42).2 (.1.4).4.2 SEER SEER. Primry nlysis cut-off dte Jnury June Februry 216 216 216 217 217 b The incidence rte of first mlignncy (number of first mlignncy events per 1 PY) ws clculted. SEER:.12 (.12.13). Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217). OCR, ocrelizumb; OLE, open-lbel extension; PY, ptient yers; SEER, Surveillnce, Epidemiology, nd End Results. http://bit.ly/husers1 21
Stndrdized incidence rte Age-stndrdized incidence rte per 1 ptient yers of femle brest cncer over time compred with SEER dtbse 1. Ph II/Ph III nd OLEs popultion OCR ll-exposure popultion.8.6.28 (.1.67).24 (.1.54).23 (.1.5).21 (.9.47).19 (.8.42).2 (.1.4).4.2 SEER. Primry nlysis cut-off dte Jnury June Februry 216 216 216 217 217 b The incidence rte of first mlignncy (number of first mlignncy events per 1 PY) ws clculted. SEER:.12 (.12.13). Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies; b Includes ptients who received ny dose of OCR during the controlled tretment nd ssocited OLE periods of the Phse II nd Phse III studies, plus VELOCE, CHORDS, CASTING nd OBOE (s of 217; clinicl cut-off dte for OBOE: June 217). OCR, ocrelizumb; OLE, open-lbel extension; PY, ptient yers; SEER, Surveillnce, Epidemiology, nd End Results. http://bit.ly/husers1 22
Post-mrketing experience Mrket Dt cut-off: Mrch 218 Estimted number of ptients on OCR Exposure (PY) Rte of ftlities per 1 PY (95% CI) 37,171 14,67.28 (.21.4) Mortlity rtes from observtionl nd dtbse studies in the overll MS popultion between 1968 nd 215 rnged from.37 to.9 per 1 PY 1,2 Up to April 25, 218: No unconfounded cses of PML with ocrelizumb hve been reported Two confirmed cses of crry-over PML Both cses hve been reported by the treting physicins nd submitted to the regultors s relted to the previous tretment with either ntlizumb (cse 1) or fingolimod (cse 2) Exposure from compssionte-use progrm not ccounted for. CI, confidence intervl; MS, multiple sclerosis; OCR, ocrelizumb; PML, progressive multifocl leukoencephlopthy; PY, ptient yers. 1. Lery E, et l. PLoS One 215;1:e13233; 2. Goodin DS, et l. PLoS One 214;9:e1527; 3. Huser SL, et l. ECTRIMS 217; Poster 676. http://bit.ly/husers1 23
Conclusions The updted sfety profile in the ocrelizumb MS ll-exposure popultion is generlly consistent with tht seen during the controlled tretment period in the RMS nd PPMS popultions In the ocrelizumb ll-exposure popultion, the pooled RMS popultion nd the PPMS popultion, rtes per 1 PY of serious infections by yer fluctuted over time, without ny sustined increse One serious opportunistic infection (systemic Psteurell infection) hs been confirmed in ptients from ocrelizumb clinicl trils, s of 217 In the updted exposure period to 217, the rte of mlignncies in ocrelizumb-treted ptients remined within the rnge reported in epidemiologicl dt Long-term follow-up nd post-mrketing requirement studies will monitor ptient sfety, including identified nd potentil risks, in ptients with MS receiving ocrelizumb MS, multiple sclerosis; PPMS, primry progressive multiple sclerosis; PY, ptient yers; RMS, relpsing multiple sclerosis. http://bit.ly/husers1 24
Acknowledgments We would like to thnk ll ptients, their fmilies, the investigtors, the independent dt monitoring committees, NeuroRx Reserch (Montrel, QC, Cnd), nd the Study Steering Committees who prticipted in these trils nd the ssocited open-lbel extensions: Phse II, OPERA I, OPERA II, ORATORIO, VELOCE, CHORDS, CASTING, OBOE This reserch ws sponsored by F. Hoffmnn-L Roche Ltd, Bsel, Switzerlnd. Writing nd editoril ssistnce for this presenttion ws provided by Articulte Science, UK, nd funded by F. Hoffmnn-L Roche Ltd, Bsel, Switzerlnd. http://bit.ly/husers1 25