Roche Holding Ltd · SIX:RO
Roche — Technical Presentation (2019)
16 slides from Roche's technical presentation, 2019
Slide 1: Phase II Study of Obinutuzumab plus MMF in Active Class III or IV Lupus Nephritis
https://bit.ly/32V3ngT A Phase II Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Obinutuzumab or Placebo in Combination with Mycophenolate Mofetil in Patients with Active Class III or IV Lupus Nephritis Richard Furie,1 Gustavo Aroca,2 Analía Alvarez,3 Hilda
Slide 2: Disclosures
Disclosures • This study was funded by Genentech, Inc. • R Furie: Genentech. • BH Rovin: Genentech, Aurinia, BristolMyersSquibb, Biogen, Pfizer, Eli Lilly, GlaxoSmithKline, Mallinckrodt, EMD Serono, Omeros, Calliditas, Retrophin, BioMarin. • G Aroca, A Alvarez, H Fragoso-Loyo, E Zuta Santillan, A Ma
Slide 3: B-cell depletion in lupus nephritis
B-cell depletion in lupus nephritis • End-stage renal disease risk from proliferative lupus nephritis (LN) remains high1 • B-cells are central to LN pathogenesis but RCTs of Type I anti-CD20 antibodies rituximab and ocrelizumab showed mixed results2,3 • Variability in B-cell depletion with Type I an
Slide 4: Obinutuzumab
Obinutuzumab • Obinutuzumab is a humanized Type II anti-CD20 approved for combination treatment of CLL and follicular lymphoma1 • Enhanced B-cell depletion vs. rituximab and ofatumumab: • Glycoengineering: Up to 100x antibody-dependent cytotoxicity2,3 • Type II binding conformation: Greater direct c
Slide 5: NOBILITY design
NOBILITY design 104 week double-blind period Obinutuzumab 1000 mg + MMF (n=63) 1:1 All patients received MMF, 1000 mg methylprednisolone, and a prednisone taper* Placebo + MMF (n=62) 0 2 4 8 12 24 26 36 Week 52 Week 76 104 OBI or PBO infusions Key inclusion criteria: Key exclusion criteria: Primary
Slide 6: Baseline characteristics
Baseline characteristics Obinutuzumab + MMF (n=63) Placebo + MMF (n=62) Female 55 (87%) 51 (82%) Race/ethnicity Hispanic 42 (67%) 49 (79%) White 10 (16%) 5 (8%) Black 6 (10%) 4 (6%) Other 5 (8%) 4 (7%) Prior history of LN 32 (51%) 32 (52%) Class IV LN 49 (78%) 44 (71%) Concomitant class V LN 20 (32%
Slide 7: Exposure and disposition
Exposure and disposition Obinutuzumab + MMF (n=63) Placebo + MMF (n=62) Received four study drug infusions 57 (90%) 54 (87%) MMF exposure – median 2.0 g/day 2.0 g/day Corticosteroid exposure 4008 mg 4009 mg through Week 52 – median Completed 52 weeks of follow-up 59 (94%) 56 (90%) Completed 76 weeks
Slide 8: Renal response endpoints
Obinutuzumab + MMF Renal response endpoints Placebo + MMF Complete renal response (CRR) Overall renal response (CRR or PRR) Δ20%, P=0.02 Δ22%, P=0.02 Δ22%, P=0.007 56% Δ12%, P=0.11 51% 40% 35% 36% 29% 23% 18% Week 52 Week 76 Week 52 Week 76 CRR required all of: PRR required all of: • UPCR < 0.5 • UP
Slide 9: Alternative complete response definitions at Week 76
Alternative complete response Obinutuzumab + MMF Placebo + MMF definitions at Week 76 Δ20%, P=0.02 Δ25%, P=0.003 Δ22%, P=0.007 57% 48% 40% 37% 23% 18% CRR Excluding sediment Permissive SCr criteria • UPCR < 0.5 • UPCR < 0.5 • UPCR < 0.5 • SCr ≤ ULN • SCr ≤ ULN • SCr ≤ ULN • SCr ≤ 115% of baseline •
Slide 10: CRR over time
CRR over time OBI or PBO infusions * P < 0.2; ** P < 0.05; *** P < 0.01 for comparison vs. placebo. 10
Slide 11: Mean change in laboratory values
Obinutuzumab + MMF Mean change in laboratory values Placebo + MMF Last observation prior to treatment failure is applied for missing data. Comparisons were adjusted for stratification factors (region, race). * P < 0.02; ** P < 0.05; *** P < 0.01 for comparison vs. placebo. 11
Slide 12: B-cell depletion in peripheral blood
B-cell depletion in peripheral blood Mean CD19+ count Percent with CD19+ count ≤ 5 cells/μL Obinutuzumab + MMF Week 2 96% PBO + MMF Week 4 96% Week 12 94% Week 24 93% OBI + MMF Week 52 94% 12
Slide 13: B-cell subsets
Obinutuzumab + MMF B-cell subsets Placebo + MMF Memory B-cells: CD45+, CD19+, CD27+ Naïve B-cells: CD45+, CD19+, IgD+, CD27-, CD38dim/- Plasmablasts: CD45+, CD19+, CD27+, CD38bright 13
Slide 14: Safety summary at Week 76 data cut
Safety summary at Week 76 data cut Obinutuzumab + MMF (n=64) Placebo + MMF (n=61) Follow-up duration, wks – median 86.6 77.1 Any adverse event 56 (88%) 55 (90%) 1 (2%) 4 (7%) Deaths GI perforation GI bleed, SLE, PML, Resp. infection Serious adverse events 15 (23%) 18 (30%) Serious infection events 4
Slide 15: Conclusions
https://bit.ly/32V3ngT Conclusions • NOBILITY met its primary and key secondary endpoints • Obinutuzumab resulted in clinically-meaningful benefits over SOC alone on renal response through Week 76 • Significant improvements in serologies and proteinuria were also observed • Obinutuzumab resulted in
Slide 16: We thank all study participants and investigators
We thank all study participants and their families, and our investigators and study coordinators NOBILITY Investigators Dhawan, Richa Lafayette, Richard A. Podoll, Amber Dolff, Sebastian Lee, Steve Quintana Porras, Luis Alvarez, Analia Doria, Andrea Lidar, Merav Ramos-Remus, Cesar Amit Vazina, Mirit