Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — AASLD 2016
14 slides from Alnylam Pharmaceuticals's conference presentation, Nov 11, 2016
Slide 1: EXPLORE: Natural History Study of Acute Hepatic Porphyria Patients with Recurrent Attacks
EXPLORE: A Prospective, Multinational Natural History Study of Acute Hepatic Porphyria Patients with Recurrent Attacks 11 November 2016 | AASLD 2016 | Boston, USA 1
Slide 2: Authors
Authors • Anderson KE (University of Texas, Medical Branch, Galveston, • Minder EI (Stadtspital Triemli, Zentrallabor, Switzerland), Texas), • Windyga J (Instytut Hematologii i Transfuzjologii, Poland), • Bloomer JR (University of Alabama, Birmingham, Alabama), • Martasek P (Univerzity Karlovy v Pra
Slide 3: Abstract
Abstract Introduction: The acute hepatic porphyrias (AHP), including acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP), are due to a deficiency in the liver of one of the eight enzymes required for heme biosynthesis. Induction of the first enzyme 5-ami
Slide 4: Acute Hepatic Porphyria Disease Overview
Acute Hepatic Porphyria Disease Overview Acute Hepatic Porphyria (AHP)1,2 • Inborn errors of heme synthesis from liver enzyme Glycine Succinyl CoA defects ALA Synthase 1 Attack • AIP most common, with prevalence 2-5 per (ALAS1) Triggers (e.g. drugs, stress) 100,000, approximately 5-10% manifest δ- A
Slide 5: Study Design Overview
Study Design Overview Study Design Key Objectives • Observational, multinational, prospective natural history • Characterize natural history and current AHP management study ◦ Medical history and medication usage Key Eligibility Criteria ◦ Porphyria signs and symptoms • Males or Females ≥ 18 years o
Slide 6: Enrollment and Demographics
Enrollment and Demographics Demographics Result AHP Disease Number Affected Enrollment (N=112) Characteristics (%) Age, mean 39 years AIP 104 (93) 60 Sex, n (%) VP 5 (4) USA – 44% Female 100 (89) 50 Male 12 (11) HCP 3 (3) Patients Enrolled 40 Europe – 56% Race, n (%) Genotypes Represented 30 AIP 63
Slide 7: Baseline Data on Diagnosis and Porphyria Manifestations
Baseline Data on Diagnosis and Porphyria Manifestations Patient Self-Assessment Questionnaire Patient Reported Attack Data Mean (median; range) Number in last 12 months 9.5 (6; 0-54) Years Since Diagnosis 2% Unknown Patient Reported Symptoms/Treatment Number (%) Known attack triggers 98 (88) 18% Pro
Slide 8: Symptoms Associated with Attacks
8 Symptoms Associated with Attacks (% of patients) • • 10 30 40 50 60 70 80 90 20 0 100 Abdominal pain Back pain Arm/Leg pain Muscle pain Headache Pain Data as of 17 AUG 2016 Numbness Skin pain Other pain Blisters/Rashes Tiredness Screening Questionnaire Trouble sleeping Anxiety Trouble concentratin
Slide 9: On Study Attack Number and Treatment
On Study Attack Number and Treatment 95 patients experienced 404 attacks* Treatment Location 25 % Attacks Location Total EU US 20 Attack Duration: 7.2 days (1.3-40.5) mean (range) Home 32% 36% 26% Patients 15 Healthcare facility 68% 64% 73% Unknown 0.2% 0% 0.6% 10 5 0 Treatment Type 0 2 4 6 8 10 12
Slide 10: Porphyria Disease Biomarkers
Porphyria Disease Biomarkers Paired Urinary ALA/PBG Samples Asymptomatic Attack Maximum Attack Maximum Fold Above Biomarkers N Mean (range) Mean (range) Asymptomatic (range) PBG (mmol/mol Cr) 62 30.6 (0.5-111.2) 56.6 (0.3-843.9) 3.5 (0.1-32) ALA (mmol/mol Cr) 59 29.6 (1.7-109.6) 66.8 (2.2-1016.6) 3.
Slide 11: Quality of Life: EQ-5D-5L at 6 Months (Asymptomatic)
Quality of Life: EQ-5D-5L at 6 Months (Asymptomatic) No problems Slight problems Motility/Walking Moderate problems N=100 Severe Problems 17% Unable to walk No problems Slight problems Self-Care Moderate problems Severe Problems 5% Unable to wash or dress myself Moderate or No problems Greater Sligh
Slide 12: Porphyria-Related Reported Healthcare Utilization
Porphyria-Related Reported Healthcare Utilization Current Function in Past Year % Comments Live at home with no special care 50% Handling most personal needs (25%), need assistance (21%), bed bound (3%) Currently working full-time 30% 27% on disability or unemployed Had any missed days of work? 85%
Slide 13: EXPLORE Study Summary
EXPLORE Study Summary AHP Disease Findings and Unmet Need Baseline Demographics and Disease Characteristics • Patients reported 9.5 attacks in the prior year, with pain as a cardinal feature in 100% of attacks • Approximately 65% of patients experience porphyria symptoms between attacks, with almost
Slide 14: References
References 1Bonkovsky HL, et al. Am J Med. 2014;127(12):1233-41. 2Elder G, et al. J Inherit Metab Dis. 2013;36(5):849-57. 3Chan A, et al. Mol Ther Nucleic Acids. 2015;4:e263. 4Lin FJ, et al. BMC Med Res Methodol. 2014;14:78. 5Nordenfelt P, et al. Allergy Asthma Proc. 2014;35(2):185-90. 6Lubetkin EI,