-Findings From the ILLUMINATE-C Phase 3 Study Showed Substantial Reductions in Plasma Oxalate in PH1 Patients with End-Stage Kidney Disease, Including Patients on Hemodialysis-

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) and Type II Filing Variation to the European Medicines Agency (EMA) for lumasiran, an investigational RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) – the gene encoding glycolate oxidase (GO) – for the reduction of plasma oxalate in the treatment of patients with advanced primary hyperoxaluria type 1 (PH1).

“Compromised renal function in patients with advanced PH1 often leads to elevated levels of plasma oxalate and subsequent pathologic deposition of oxalate in multiple organs, including the bones, eyes, heart, and skin – a highly morbid and potentially fatal condition known as systemic oxalosis. Treatment options for these patients are limited to intensive hemodialysis and liver/kidney transplantation. With that in mind, we believe the ILLUMINATE-C data package demonstrates the potential for lumasiran to provide a therapeutic option that substantially reduces plasma oxalate levels that result in systemic oxalosis in adult and pediatric PH1 patients with advanced disease, including for patients on hemodialysis,” said Jeroen Valkenburg, General Manager, Lumasiran program at Alnylam.

The applications to the FDA and EMA are based on positive results from the ILLUMINATE-C single-arm, open-label Phase 3 study of lumasiran in patients of all ages with advanced PH1. The six-month primary analysis results from the study were presented in November 2021 at the American Society of Nephrology (ASN) Kidney Week annual meeting and showed a substantial reduction in plasma oxalate from baseline in PH1 patients with chronic kidney disease (CKD) stage 3b-5, with or without dialysis. The most common drug-related adverse events were injection site reactions, all of which were mild and transient.

OXLUMO® (lumasiran) INDICATION AND IMPORTANT SAFETY INFORMATION

Indication OXLUMO is indicated for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels in pediatric and adult patients.

Important Safety Information

Adverse Reactions

The most common adverse reaction that occurred in patients treated with OXLUMO was injection site reaction (38%). Symptoms included erythema, pain, pruritus, and swelling.

Pregnancy and Lactation

No data are available on the use of OXLUMO in pregnant women. No data are available on the presence of OXLUMO in human milk or its effects on breastfed infants or milk production. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for OXLUMO and any potential adverse effects on the breastfed child from OXLUMO or the underlying maternal condition.

For additional information about OXLUMO, please see the full U.S.Prescribing Information.

About Lumasiran Lumasiran is a subcutaneously administered RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) in development for the treatment of advanced 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 regulatory approvals from the U.S. Food and Drug Administration (FDA) for the treatment of PH1 to lower urinary oxalate levels in pediatric and adult patients and from the European Medicines Agency (EMA) for the treatment of PH1 in all age groups under the brand name OXLUMO®.

About ILLUMINATE-C Phase 3 Study ILLUMINATE-C (NCT04152200) is a single arm, open-label, multinational Phase 3 study evaluating the safety and efficacy of lumasiran in PH1 patients of all ages with severe renal impairment (eGFR ≤ 45 mL/min/1.73m2 or elevated serum creatinine for patients