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Re: Alnylam Receives Positive CHMP Opinion for OXLUMO™ (lumasiran) - PRAlnylam Presents Positive Results from ILLUMINATE-B Phase 3 Study in Pediatric Patients with Primary Hyperoxaluria Type 1 at the American Society of Nephrology Kidney WeekBUSINESS WIRE 10:00 AM ET 10/22/2020 – Lumasiran Demonstrated a 72 Percent Mean Reduction in Urinary Oxalate and Improvements in Nephrocalcinosis in ILLUMINATE-B Phase 3 Study in Children Under the Age of Six and as Young as Three Months – – Alnylam Also Presents New Results from the 12-Month Extension Period of the ILLUMINATE-A Pivotal Study, Showing Sustained Reduction in Urinary Oxalate Levels and Evidence for a Decrease in the Rate of Renal Stone Events in Patients Treated with Lumasiran – – Long-Term Results from the Ongoing Phase 2 Open-Label Extension Study Provide Additional Evidence for Sustained Reduction in Urinary Oxalate Levels and Acceptable Safety Profile – Lumasiran is under review by the “We are delighted to present these positive data from ILLUMINATE-B that reinforce previously reported clinical study findings for lumasiran and underscore its potential to be an important treatment option for patients of all ages with PH1, a devastating and potentially fatal disease with no approved pharmaceutical treatment options,” said “Pathologic overproduction of oxalate by the liver is the root cause of morbidity and mortality associated with PH1. There is strong evidence in the literature to suggest that levels of urinary oxalate correlate with clinical outcomes in patients with this ultra-rare disease. With that in mind, I am pleased to see the reduction in urinary oxalate levels in response to lumasiran in all three studies presented at this year’s meeting. More broadly, I am encouraged by the promise that these findings hold for my patients living with this condition,” said ILLUMINATE-B 6-Month Results Alnylam presented positive efficacy and safety results from the 6-month primary analysis (N=18) of the ILLUMINATE-B Phase 3 study of lumasiran in infants and children under the age of 6, with the youngest patient enrolled at 3 months of age. The efficacy results and safety profile of lumasiran were found to be similar to those observed in adults and children 6 years or older in the ILLUMINATE-A study. Treatment with lumasiran in ILLUMINATE-B led to a 72 percent mean reduction in spot urinary oxalate:creatinine ratio from baseline to Month 6, averaged across months 3 to 6 – the primary endpoint of the study. Lumasiran also demonstrated positive results across secondary endpoints, including proportion of patients (9/18 or 50 percent) achieving urinary oxalate levels at or below 1.5 times ULNa. Preliminary analysis of exploratory endpoints indicated improvements in nephrocalcinosis in 8 out of 18 patients (44 percent), while estimated glomerular filtration rates (eGFR) remained stable. At baseline, 14 of 18 patients had nephrocalcinosis. After 6 months of lumasiran treatment, no patients worsened, 10 remained stable, and eight showed bilateral (3 out of 8) or unilateral (5 out of 8) improvements in nephrocalcinosis. As expected, given the 6-month duration of the study, there was no change in the rate of renal stone events (RSEs)b . Lumasiran had an acceptable safety profile in infants and young children under the age of six. There were no deaths, severe adverse events, discontinuations of treatment or withdrawals from the study. One patient had a serious adverse event (SAE) of viral infection that was considered not related to lumasiran by the study investigator. The most common drug-related adverse events (AEs) were mild and transient injection site reactions (ISRs) reported in 3 of 18 (17 percent) patients. No clinically relevant changes in laboratory measures (including liver function tests), vital signs, or electrocardiograms related to lumasiran were observed. ILLUMINATE-A 12-Month Results As of the data cut-off date of In an exploratory analysis, reductions in oxalate levels were associated with lower rates of RSEb in lumasiran treated patients in both lumasiran/lumasiran and placebo/lumasiran groups. The safety profile of lumasiran remained consistent with ongoing dosing (233 doses) and 9.9 months of mean exposure (range 2.8-15.1 months). There were no deaths, SAEs, treatment interruptions or discontinuations related to lumasiran. One patient had an SAE of urosepsis that was not related to study drug. Mild ISRs were the most common drug-related AE reported in at least 10 percent of patients. Most common ISR symptoms included erythema, pain, pruritus, or swelling at the injection site. No clinically relevant changes in laboratory measures (including liver function tests), vital signs, and electrocardiograms related to lumasiran were observed. Phase 2 OLE Results Additional positive data were also presented from the ongoing Phase 2 OLE study of lumasiran demonstrating the long-term efficacy and safety of lumasiran with up to 22 months of exposure (range: 11-22 months; median: 15 months). As of Lumasiran had an acceptable safety profile. There were no deaths, severe AEs, or AEs leading to discontinuation of treatment. There were no drug-related SAEs. The most common drug-related AEs were mild ISRs. No clinically significant laboratory changes related to lumasiran were reported. Post-hoc analysis of renal stones showed that long-term treatment with lumasiran resulted in a decline in the number of patients experiencing renal stones. In the 12 months prior to study entry, 6/20 patients (30 percent) reported renal stones. In the Phase 1/2 Part B study where renal stones were captured as AEs, 4/20 patients (20 percent) reported AEs of renal stones during the initial 5-month period, and no patients (0/20) reported AEs of renal stones during the Phase 2 OLE with up to 22 months of treatment. Additional findings on real-world disease manifestations and healthcare resource use among patients with PH1 were also presented based on a retrospective multinational study of physician chart reviews. To view all data presented by Alnylam at ASN Kidney Week, please visit www.alnylam.com/capella. Lumasiran has received U.S. and EU Orphan Drug Designations, Breakthrough Therapy and Rare Pediatric Disease Designations from the The Company is also conducting ILLUMINATE-C – a global open-label Phase 3 study of lumasiran in PH1 patients of all ages with advanced renal disease, including patients on dialysis, with topline results expected in 2021. a Upper limit of normal or ULN = 0.514 mmol/24 hr/1.73m2; 1.5 x ULN = 0.771 mmol/24 hr/1.73 m2 About ILLUMINATE-A Phase 3 Study ILLUMINATE-A (NCT03681184) is a six-month randomized, double-blind, placebo-controlled, global, multicenter Phase 3 study (with a 54-month extension period) to evaluate the efficacy and safety of lumasiran in 39 patients, age six and older, with a documented diagnosis of PH1. Patients were randomized 2:1 to receive three monthly doses of lumasiran or placebo followed by quarterly doses at 3 mg/kg. The primary endpoint was the percent change in 24-hour urinary oxalate excretion from baseline to the average of months 3 to 6 in the patients treated with lumasiran as compared to placebo. Treatment arms were stratified at randomization based upon mean 24-hour urinary oxalate during screening (≤1.7 or >1.7 mmol/24hr/1.73m2). Key secondary and exploratory endpoints were designed to evaluate additional measures of urinary oxalate, plasma oxalate, estimated glomerular filtration rate (eGFR), nephrocalcinosis, renal stone events, safety and tolerability. About ILLUMINATE-B Phase 3 Study ILLUMINATE-B (NCT03905694) is a single arm, open-label, multicenter Phase 3 trial to evaluate the efficacy and safety of lumasiran in 18 patients with PH1 under the age of six (range: 3-72 months), with an estimated glomerular filtration rate (eGFR) of greater than 45 mL/min/1.73 m2 or normal serum creatinine if less than 12 months old, at nine study sites, in five countries around the world. Lumasiran was administered according to a weight-based dosing regimen. The primary efficacy endpoint of the study was the percent change from baseline to Month 6 in spot urinary oxalate:creatinine ratio averaged across Months 3 to 6. At six months, relative to baseline, lumasiran demonstrated a clinically meaningful reduction in spot urinary oxalate:creatinine ratio. Reduction of urinary oxalate relative to baseline was consistent across all three body weight categories (less than 10 kg; 10 kg to less than 20 kg, and 20 kg or higher). About Lumasiran Lumasiran is an investigational, subcutaneously administered RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) in development for the treatment of primary hyperoxaluria type 1 (PH1). HAO1 encodes glycolate oxidase (GO). Thus, by silencing HAO1 and depleting the GO enzyme, lumasiran inhibits production of oxalate – the metabolite that directly contributes to the pathophysiology of PH1. Lumasiran utilizes Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index. Lumasiran has received both U.S. and EU Orphan Drug Designations, Breakthrough Therapy Designation from the |
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