Biogen Inc. · NASDAQ:BIIB
Biogen — Technical Presentation (December 2016)
20 slides from Biogen's technical presentation, Dec 12, 2016
Slide 1: Aducanumab Titration Dosing Regimen: 12-Month Interim Analysis from PRIME
Interim analysis presented at CTAD 2016 Aducanumab Titration Dosing Regimen: 12-Month Interim Analysis from PRIME, a Randomized, Double-Blind, Placebo-Controlled Phase 1b Study in Patients With Prodromal or Mild Alzheimer’s Disease Vissia Viglietta,1 John O’Gorman,1 Leslie Williams,1 Tianle Chen,1 A
Slide 2: Disclosures
Interim analysis presented at CTAD 2016 Disclosures This study is funded by Biogena VV, JO, LW, TC, AE, PC, SBH, and AS are employees and shareholders of Biogen CH and RMN are employees and shareholders of Neurimmune aMedical writing support for this presentation was provided by Erin Bekes, PhD,
Slide 3: Introduction
Interim analysis presented at CTAD 2016 Introduction Aducanumab is a human monoclonal antibody selective for aggregated forms of Aβ, including soluble oligomers and insoluble fibrils PRIME is an ongoing Phase 1b study assessing the safety, tolerability, PK and PD of aducanumab in patients with p
Slide 4: PRIME Study Design: Placebo-Controlled and LTE Periods
Interim analysis presented at CTAD 2016 1 mg/kg 3 mg/kg Placebo Titration (ApoE ε4 carriers) Placebo (ApoE ε4 carriers) 6 mg/kg Placebo PRIME Study Design: Placebo-Controlled and LTE Periods Randomization: 3:1 active: placebo within cohorts, fixed-dose cohorts stratified by ApoE ε4 status Planne
Slide 5: Titration Dosing Regimen in the 12-Month Placebo-Controlled Period
Interim analysis presented at CTAD 2016 Titration Dosing Regimen in the 12-Month Placebo-Controlled Period 3 mg/kg 6 mg/kg 10 mg/kg Study week: 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Dose (mg/kg): Placebo 1 1 3 3 3 3 6 6 6 6 6 10 10 10 1 mg/kg By Week 52 average expected dose = 5.3 mg/kg By Week 24
Slide 6: Patient Disposition at Months
Interim analysis presented at CTAD 2016 Patient Disposition at 12 Months AE, adverse event Analysis of data from all cohorts up to Week 54 Randomized Dosed Discontinued treatment AE Lost to follow-up Disease progression Consent withdrawn Investigator decision Death Other 197 randomized (by cohort) 1
Slide 7: Baseline Disease Characteristics
Interim analysis presented at CTAD 2016 Baseline Disease Characteristics AD, Alzheimer’s disease; SD, standard deviation; SUVR, standardized uptake value ratio aCholinesterase inhibitors and/or memantine. Aducanumab Placebo (n=48) 1 mg/kg (n=31) 3 mg/kg (n=32) 6 mg/kg (n=30) 10 mg/kg (n=32) Titratio
Slide 8: PET Amyloid Imaging
Interim analysis presented at CTAD 2016 PET AMYLOID IMAGING
Slide 9: Aducanumab Reduces Amyloid Plaques
Interim analysis presented at CTAD 2016 Aducanumab Reduces Amyloid Plaques Nominal p values: * P<0.05; **P<0.01; ***P<0.001 vs placebo. 1. Ostrowitzki et al. Arch Neurol 2012 Analyses based on observed data. ANCOVA for change from baseline with factors of treatment, laboratory ApoE ε4 status (carrie
Slide 10: Clinical Endpoints
Interim analysis presented at CTAD 2016 CLINICAL ENDPOINTS
Slide 11: Effect of Aducanumab on Clinical Decline as Measured by CDR-SB
Interim analysis presented at CTAD 2016 Effect of Aducanumab on Clinical Decline as Measured by CDR–SB (exploratory endpoint) CDR-SB is an exploratory endpoint. Analyses based on observed data. ANCOVA for change from baseline with factors of treatment, laboratory ApoE ε4 status (carrier and non-carr
Slide 12: Effect of Aducanumab on Clinical Decline as Measured by MMSE
Interim analysis presented at CTAD 2016 Effect of Aducanumab on Clinical Decline as Measured by MMSE (exploratory endpoint) MMSE is an exploratory endpoint. Analyses based on observed data. ANCOVA for change from baseline with factors of treatment, laboratory ApoE ε4 status (carrier and non-carrier)
Slide 13: Safety and Tolerability
Interim analysis presented at CTAD 2016 SAFETY AND TOLERABILITY
Slide 14: No New Safety Signals Identified in Titration Cohort
Interim analysis presented at CTAD 2016 No New Safety Signals Identified in Titration Cohort During 12-Month Placebo-Controlled Period No new safety signals were identified in the titration cohort As previously presented for the fixed-dose cohorts: - The most common AE/SAE was ARIA - Other AEs/S
Slide 15: Dose Titration Slightly Attenuated Incidence of ARIA-E Versus Higher Fixed Doses
Interim analysis presented at CTAD 2016 Dose Titration Slightly Attenuated Incidence of ARIA-E Versus Higher Fixed Doses Incidence of ARIA based on MRI. ARIA-E, ARIA‒vasogenic edema; ARIA-H, ARIA‒microhemorrhages, macrohemorrhages, or superficial siderosis; MRI, magnetic resonance imaging Placebo Ad
Slide 16: Timing of ARIA-E in the Titration Cohort
Interim analysis presented at CTAD 2016 Timing of ARIA-E in the Titration Cohort 8 subjects had ARIA-E in 3 or 6 mg/kg stage. 13 subjects reached 10 mg/kg without ARIA-E - Currently 12 of the 13 subjects are active in the study • All 12 have received ≥10 doses of 10 mg/kg 1 1 3 3 3 3 6 6 6 6 6 1
Slide 17: Most Titration Patients with ARIA-E Continued Treatment
Interim analysis presented at CTAD 2016 Most Titration Patients with ARIA-E Continued Treatment Among ApoE ε4 carriers with ARIA-E, 4/11 (36%) in the 10 mg/kg group continued treatment 7/9 (78%) in the 6 mg/kg group continued treatment 6/8 (75%) in the titration group continued treatment Aduca
Slide 18: ARIA-E Characteristics in the Titration Cohort
Interim analysis presented at CTAD 2016 ARIA-E Characteristics in the Titration Cohort Majority of cases occurred within the first 5 months of treatment 75% of events were asymptomatic 2 patients (25%) had mild symptoms that resolved MRI findings typically resolved within 412 weeks
Slide 19: Summary
Interim analysis presented at CTAD 2016 Summary Both titration and fixed doses of aducanumab significantly reduced amyloid plaque burden following 12 months of treatment versus placebo Clinical effects with titrated aducanumab were generally consistent with findings in the fixed-dose cohorts - S
Slide 20: Acknowledgments
Interim analysis presented at CTAD 2016 Acknowledgments We thank all the patients and their family members participating in the aducanumab studies, as well as the investigators and their staff conducting these studies.