Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — ERA-EDTA 2022
16 slides from Alnylam Pharmaceuticals's conference presentation, May 13, 2022
Slide 1: Lumasiran for Patients With Primary Hyperoxaluria Type 1 With Impaired Kidney Function
Lumasiran for Patients With Primary Hyperoxaluria Type 1 With Impaired Kidney Function: Data From the 6-Month Analysis of the Phase 3 ILLUMINATE-C Trial Jaap W. Groothoff,1 Mini Michael,2 Hadas Shasha-Lavsky,3 John C. Lieske,4 Yaacov Frishberg,5 Eva Simkova6, Anne-Laure Sellier-Leclerc,7 Arnaud Devr
Slide 2: Disclosures
Disclosures JW Groothoff: consultancy fees from Alnylam Pharmaceuticals and study grants F Guebre-Egziabher: principal investigator for Alnylam Pharmaceuticals from Alnylam Pharmaceuticals, Dicerna Pharmaceuticals, and uniQure and Amgen. Pharmaceuticals. SA Bakkaloglu: no disclosures to report. M Mi
Slide 3: Primary Hyperoxaluria Type 1 and Lumasiran
Primary Hyperoxaluria Type 1 and Lumasiran • PH1 is characterized by excessive hepatic oxalate Defect in PH1 Lumasiran production due to a deficiency in the hepatic CYTOSOL peroxisomal enzyme AGT1,2 Liver Glyoxylate Glycolate Glycine AGT GO • Patients with PH1 suffer from recurrent kidney Pyruvate A
Slide 4: PH1 and GO Blockade by Lumasiran
PH1 and GO Blockade by Lumasiran • Decrease in glyoxylate and oxalate and further increase in glycolate X LDHA oxalate X HOGA, 4-hydroxy-2-oxoglutarate aldolase; LDHA, lactate dehydrogenase A; NADP+, nicotinamide adenine dinucleotide phosphate; NADPH, reduced nicotinamide adenine dinucleotide phosph
Slide 5: Primary Hyperoxaluria Type 1 and Lumasiran
Primary Hyperoxaluria Type 1 and Lumasiran • Reductions in UOx were observed in patients with Defect in PH1 Lumasiran PH1 in ILLUMINATE-A (age ≥6 years and eGFR CYTOSOL ≥30 mL/min/1.73m2)1 and ILLUMINATE-B (age Liver Glyoxylate Glycolate <6 years and eGFR >45 mL/min/1.73m2 [≥12 months] Glycine AGT A
Slide 6: ILLUMINATE-C Study Design
ILLUMINATE-C Study Design PATIENT POPULATION 6-MONTH PRIMARY 54-MONTH (N=21) ANALYSIS PERIOD EXTENSION PERIOD qM × 3 loading dose, then qM or q3M qM or q3M maintenance maintenance dosing by weighta dosing by weighta • Full-term infants to adults • Genetically confirmed diagnosis of PH1 Cohort Ab Coh
Slide 7: Baseline and Clinical Characteristics
Baseline and Clinical Characteristics • 21 patients across 13 sites in 10 countries were enrolled in the study; all completed the 6-month primary analysis period Cohort A Cohort B All Treated Baseline/Clinical Characteristic (N=6) (N=15) (N=21) Age at consent, median (range), years 9 (0–40) 6 (1–59)
Slide 8: Efficacy: Primary Endpoint
Efficacy: Primary Endpoint Primary Endpoint: Mean (SEM) Percent Change From Baseline in POx 20 Percent Change From Baseline Cohort A (N=6) Cohort B (N=15) LS mean percent reduction in POx in Plasma Oxalate 0 from baseline to Month 6a: –20 Cohort A: 33.3% –40 Cohort B: 42.4% –60 BL M1 M2 M3 M4 M5 M6
Slide 9: Efficacy: Secondary Endpoint
Efficacy: Secondary Endpoint Secondary Endpoint: Mean (SEM) Actual POx Values 165 Cohort A (N=6) Cohort B (N=15) 150 Plasma Oxalate (µmol/L) 135 120 LS mean absolute 105 reduction in POx from 90 baseline to Month 6: 75 60 Cohort B: 48.33 µmol/L 45 30 Cohort A: 35.28 µmol/L 15 0 BL M1 M2 M3 M4 M5 M6
Slide 10: Additional Outcomes During the 6-Month Primary Analysis Period
Additional Outcomes During the 6-Month Primary Analysis Period • Cardiac measures of systemic oxalosis, as assessed by echocardiography • Medullary nephrocalcinosis by kidney ultrasound • Kidney stone event rates • Burdensome symptoms of PH1 Lumasiran for Patients With Primary Hyperoxaluria Type 1 W
Slide 11: LVEF and GLS With Lumasiran Treatment
LVEF and GLS With Lumasiran Treatment • Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were chosen as cardiac measures of systemic oxalosisa • Abnormalities and improvements were predefined Abnormal LVEF (LVEF <55%) • Among patients with abnormal LVEF at baseline, at
Slide 12: Kidney Stone Event Rates
Kidney Stone Event Rates Cohort A (N=6) Cohort B (N=15) 5.0 5.0 Historicala Historicala per Person-Year (95% CI) per Person-Year (95% CI) Kidney Stone Event Rate Kidney Stone Event Rate 4.0 Lumasiran 4.0 Lumasiran 3.20 (1.96, 5.22) 3.0 3.0 2.0 1.48 2.0 (0.55, 3.92) 1.0 1.0 0.07 0.00 (0.01, 0.71) (0.
Slide 13: Medullary Nephrocalcinosis by Ultrasonography
Medullary Nephrocalcinosis by Ultrasonography Change in Medullary Nephrocalcinosis Grade at Month 6 Among Patients With Medullary Nephrocalcinosis at Baselinea Cohort A (N=5) Cohort B (N=2) 100% 100 100 80 80 N=1 Patients (%) Patients (%) 60% 60 60 40% N=1 40 40 N=1 20 N=2 N=2 20 0% 0% 0% 0 0 Worsen
Slide 14: Most Burdensome Symptoms
Most Burdensome Symptoms • The 3 most burdensome symptoms at baseline for each patient were identified by the investigator a • Investigators subsequently noted if each patient’s most burdensome symptoms were stable/unchanged, improved, or worsened; no patient was categorized as worsened in this surv
Slide 15: Safety
Safety • The majority of AEs were mild or moderate in severity Number of Patients (%) • There were no serious or severe AEs related to Event Cohort A Cohort B All Treated lumasiran and no deaths of patients who received (N=6) (N=15) (N=21) lumasiran AEs 5 (83) 12 (80) 17 (81) • There were no treatme
Slide 16: Conclusions
Conclusions • Lumasiran treatment resulted in substantial reductions in POx in patients of all ages with PH1 and advanced kidney disease • Additional outcomes related to PH1 generally improved or remained stable with lumasiran treatment • The most common adverse event related to lumasiran was inject