Alnylam reported positive topline results from the ILLUMINATE-B pediatric Phase 3 study evaluating lumasiran for the treatment of primary hyperoxaluria type 1 (PH1) in children under the age of six, including infants. Lumasiran demonstrated a clinically meaningful reduction in spot urinary oxalate:creatinine ratio, meeting the primary endpoint. The treatment was well tolerated. Alnylam will present full data at the American Society of Nephrology Annual Meeting in October 2020.
ILLUMINATE-B is a single arm, open-label, multicenter trial that enrolled 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). Lumasiran demonstrated positive results across secondary endpoints, including additional measures of urinary and plasma oxalate. There were no serious or severe adverse events related to study drug.
Lumasiran has received U.S. and EU Orphan Drug Designations, Breakthrough Therapy and Rare Pediatric Disease Designations from the U.S. FDA, and a Priority Medicines (PRIME) designation from the European Medicines Agency (EMA). Alnylam has filed a New Drug Application (NDA) for lumasiran with the U.S. FDA. The FDA has granted a Priority Review for the NDA and has set an action date of December 3, 2020 under the Prescription Drug User Fee Act (PDUFA). In addition, the Marketing Authorization Application (MAA) for lumasiran has been submitted to and validated by the EMA and has received Accelerated Assessment designation.
Lumasiran is a 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.
About Primary Hyperoxaluria Type 1 (PH1)
PH1 is an ultra-rare disease in which excessive oxalate production results in the deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of painful and recurrent kidney stones and nephrocalcinosis. Renal damage is caused by a combination of tubular toxicity from oxalate, calcium oxalate deposition in the kidneys, and urinary obstruction by calcium oxalate stones. Compromised kidney function exacerbates the disease as the excess oxalate can no longer be effectively excreted, resulting in subsequent accumulation and crystallization in bones, eyes, skin, and heart, leading to severe illness and death. Current treatment options are very limited and include frequent renal dialysis or combined organ transplantation of liver and kidney, a procedure with high morbidity that is limited due to organ availability. Although a small minority of patients respond to vitamin B6 therapy, there are no approved pharmaceutical therapies for PH1.