Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

Filing 156

MEMORANDUM in Support re #155 MOTION for Reconsideration re #142 Order on Motion for Protective Order, OR FOR CLARIFICATION, filed by Amgen Inc.. (Attachments: #1 Exhibit 1#2 Exhibit 2#3 Exhibit 3#4 Exhibit 4#5 Exhibit 5#6 Exhibit 6#7 Exhibit 7#8 Exhibit 8#9 Exhibit 9#10 Exhibit 10#11 Exhibit 11 (part 1 of 2)#12 Exhibit 11 (part 2 of 2))(Gottfried, Michael)

Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

Doc. 156 Att. 5

Case 1:05-cv-12237-WGY

Document 156-6

Filed 11/29/2006

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EXHIBIT 5

Dockets.Justia.com

Case 1:05-cv-12237-WGY

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SA-PO205 IV C .E .R.A. (Continuous Erythropoietin Receptor Activator) Once Every 2 Weeks or Once Monthly Maintains Stable Hb Levels after Converting Directly from IV Epoetin 1-3 Tunes Per Week in Patients with CKD on Dialysis . S . Fishbane,l N. W. Levin? J. F E_ Mann,' J. L. Lewis,' M Bemardo, s N . M . Lunde,' F_ C . Dougherty! 'Winthrop Hospital, Mineola; 2Renal Research Institute, New Yoe*;- 3KfH Dialysezentrwn, Munich, Germany; 'Nephrology Associates RC, Birmingham ; =Southwest Nephroloay Associates, L_L .P, Houston; 6Twin Cities Clinical Research, Arlen Hells; 'F Hofman-La Roche Ltd, Basel Switzerland.
CE.RA ., an innovative agent with different binding properties compared to epoetin and a prolonged half-life, is in development for caarection of anemia and maintenance of Hb at extended administration intervals in CKD patients . This study examined the efficacy of IV CE .RA_ up to once monthly in maintaining stable Hb levels in dialysis patients converted directly from IV epoetin I-3z/wk. This multicenter study included dialysis patients (Z18 yr), on stable doses of IV epoetin (1-3x/wk), with stable baseline Hb (10 .5-13.0 g/dL) and adequate iron status . Patients were randomized to continue IV epoetin (n=226) or to IV C .E.R.A. lz2wk (n=223) or lx/4'vk (n=224) for 52 wk Dose was adjusted (no more frequently than lxl4wk) to maintain Hb within 1 .0 g/dL of baseline level and within l0 .0-13 .5 g/dL Patients were evaluated daring wk 29-36 and followed up during wk 37-52. Mean (SD) Hb levels were comparable in all groups at baseline (rang, 11 .9-12 .0 [0 .60.7] gldL) and during evaluation (range, 11 .7-11 .8 [1 .0-1 .1] g/dL) and follow-up (range, 11 .6-11 .8 [1 .0] g/dL) . SD of the means indicated comparable inter-patient variability in Hb between groups . Within patient mean SD values for Hb during evaluation and followup were 0.60 g/dL and 0 .79 gidL, respectively, for CE .R_A lx2wk ; 0 .56 gldL and 0.71 gldL for C .E.R .A .1xldwk ; and 0.55 g/dL and 0.66 grdL for epoetin, indicating comparable infra-patient variability in Hb across groups. In summary, once-monthly IV C .E.R.A . provided stable Hb levels, as recommended by guidelines, over the long term in patients converting directly from epoetin 1-3x/wk. These data also indicate that C .E .R.A. maintains tight control of Hb when administered at extended intervals_ Disclosure --Gr antiR esearch Support Roche ; Consultant. Roche; Scientific Advisor: Roche; Honoraria: Roche

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SA-PO207 SC C.E .R.A. (Continuous Erythropoietin Receptor Activator) Once Every 2 Weeks or Once Monthly Maintains Stable Hb Levels after Converting Directly from SC Epoetin 1-3 Times Per Week in Patients with Clt~ on Dialysis . F. Locatelli,! W. Suloaric.,T K.. Harris,* R. Selgas,* J . Kaufman,' M . Klinger,* F. Malberti,' F C . Dougherty.* fA Manzoni Hospital, Lecco, Italy; 'Jagiellonian University, Cracow', Poland; 'Leicester General Hospital, Leicester, United Kingdom ; 'Hospital Universitario La Paz, Madrid, Spain; 'TA Boston Healthcare System, Boston, M4; *Medical University Wroclaw, Poland; 'Istitufi Ospitalieri, Cremona, Italy; 'F Hoffmann-La Roche Ltd, . Basal, Switzerland
C.E.RA, an innovative agent acting differently at the receptor and with a prolonged half-life, is in development for correction of anemia and maintenance of lib 4 extended administration intervals in CSD patients . This study examined the efficacy of SC C .E.R.A. up to once monthly in maintai n g stable Hb levels in dialysis patients converted directly in from SC epoetin 1-3n/wk. This multicenter study included dialysis patients (218 yr .), on stable SC epoetin (13x/wk), with stable Hb (10.5-110 gfdL) and adequate iron status_ Patients (n572) were randomized to continue an SC epoetin (n=191) or to SC CE .R_A. he2wk (n=190) or lz/4wk (n=191) for 52 wk. Dose was adjusted to maintain Hb ±1 .0 gfdL of baseline and within 10.0-135 gidL. Patients were evaluated in wk 29-36 and followed up dining wk 37-52. Mean (SD) Hb levels were the same at baseline in all groups (11 .7 [0.7] g/dL) and remained stable during evaluation (range, 11 .4-11 .7 [1 .1-1 .2] g/dL) and follow-up (range, 115-11 .6 [1 .0-1 .1] g/dL) periods_ SD of the means indicated comparable inter-patient variability in Hb between groups_ Within patient mean SD values for Hb dining evaluation and follow-up were 0 .52 & 0.68 gfdL, respectively, for C.E .RA lx/2w& ; 0.57 & 0.76 g/dL for C.E .R_A_ lx/4wk ; & 0.57 & 0.68 g/dL for epoetin, indicating comparable infra-patient variability in Hb across groups_ These Phase ET results show that once mnnthly SC CERA provided long-team tight control of Hb, as recommended by guidel ines, in patients converting directly from epoetin 1-3x/wk over the long tem. Bymaints nin E Hb within a tight range, once-monthly C_ERA_ will decrease the time and effort needed for anemia ma agement n Disclosure --Grant/Research Support: Roche; Consultant Roche; Scientific Advisor: Roche, Amgen ; Honoraria : Roche; Advisory Board or Board of Directors : Roche

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Ski--P0212 C.E.R .A. (Continuous Erythropoie tin Receptor Activator) Administered at Extended Intervals Corrects Hb Levels in Patients with CM) on Dialysis . M. Klinger,' M. Arias,' V. Vargemezis,' A. Besarab,` W Sulowicz,s T. Gerntholte K Ciechanowski,' F. C . Dougherty.s 'Medical University, Wroclaw, Poland; :Hospital Marques de Valdeciila, Santander, Spain ; 'University Hospital, Alexandroupolis, Greece; 'Henry Ford Hospital, Detroit ; sJagiellonian University, Crakow, Poland; 'ChrisHani Baragwanath Hospital, Johannesburg South A,frica; 'Pomeranian Medical University, Szczecin, Poland;'FHoffinannLa Roche Ltd, Basel, Switzerland.
C.E .RA., an innovative agent with unique receptor activity and a prolon ged half-life, is cuuently in development to provide correction of anemia and stable maintenance of Iib levels at extended administration intervals in CKD patients . This study examined the smo tionintervalsoflxi2wkincorrectinganemia efficacy ofNC.E_RAatextended ad· and maintaining Hb levels in ESA-naive patients with CKD on dialysis. This multicenter, open-label, parallel-group study enrolled patients (Z 18 yr) with CKD on maintenance dialysis (178 on hemodialysis, 3 on peritoneal dialysis) whose baseline Hb was 8-11 gJdL and who had adequate iron status (K/DOQI, EBPG) . After screening, patients (n=181) were randomized (3 :1) to IV C .L.R.A. (t135) or epoetin alfa or beta (n=16) for 24 wk. Dose was adjusted to achieve a Hb response Cal gfdL increase and 11 g/dL) . Thepaimary efficacy parameter was the Hb response rate at the end of the correction period of 24 wk. Mean (SD) Hb levels at banlino were similar for C .E RA (9 .4 [0 .9] g/dL) and epoetin (9 .4 [0.8] gfdL). Response rates (95% CI) at the end of the correction period were 933% (87.7-96 .9) for C .ERA and 913% (79 .2-97.6) for epoetin; mean rib levels were 12.1 gldL & 12.0 g/dL, respectively. Median dose at the time of response was 0 .6 pglkgl2wk for C .E.R.A. and 123 HA givrk for epaetia. CERA. was well tolerated ; the most frequent AEs were hypertension, procedural hypotension and arteriotienous fistula site hemorrhage. AEs were similar with epoetin. This Phase HI study demonstrated that IV C .ERA 0 .6 ggAcgl2wk is effective in correcting lib levels in ESA-naive patients with CKD on dialysis, achieving target Hb levels (as recommended by guidelines) in more than 90% of patients. Disclosure ­ GrantiResearch Support Roche ; Consultant Roche; Scientific Advisor: Roche, Oriho Biotech; Honoraria: Roche