- Results Showed Substantial Reductions in Plasma Oxalate Relative to Baseline in PH1 Patients with Severe Renal Impairment, Including Those on Dialysis, and an Encouraging Safety and Tolerability Profile -

- Alnylam Intends to File Supplemental Regulatory Applications with the U.S. Food and Drug Administration and the European Medicines Agency Based on ILLUMINATE-C Results in Late 2021 -

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today positive topline results from the ILLUMINATE-C Phase 3 open-label study of lumasiran in patients of all ages with advanced primary hyperoxaluria type 1 (PH1) associated with progressive decline in renal function. Lumasiran is an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) – the gene encoding glycolate oxidase (GO) – that is being investigated for the treatment of adult and pediatric patients with advanced PH1. Results of the primary analysis at six months demonstrated substantial reduction in plasma oxalate from baseline in patients (N=21) with advanced disease, including those on hemodialysis. Elevated plasma oxalate is directly related to the pathophysiology of oxalosis and results in systemic deposition of oxalate in extra-renal tissues, potentially leading to bone fractures, cardiomyopathy, impaired erythropoiesis, vision loss, skin ulcers, and other serious manifestations1. The safety and tolerability profile of lumasiran following six months of treatment is encouraging across all ages, with no drug related serious adverse events (SAEs) and injection site reactions (ISRs) as the most common adverse event (AE).

“People with advanced PH1 suffer from severely impaired kidney function and may require an intensive dialysis regimen as a bridge to receiving a combined liver/kidney transplant – a procedure associated with high morbidity and lifelong immunosuppression. In ILLUMINATE-C, lumasiran reduced elevated levels of plasma oxalate that can lead to the morbidity and mortality associated with systemic oxalosis in this particularly vulnerable patient population,” said Jeroen Valkenburg, General Manager, Lumasiran program at Alnylam. “Through the ILLUMINATE clinical program, we are hoping to establish that lumasiran may be a therapeutic option for PH1 patients regardless of age or disease severity, including patients on hemodialysis. We look forward to reporting complete data from the ILLUMINATE-C study at a medical congress later this year.”

“Patients with PH1 face devastating health challenges, especially those approaching or experiencing kidney failure, and these new results from the ILLUMINATE clinical development program signal hope to some of the sickest and most severely impacted individuals in this patient community,” said Kim Hollander, Executive Director of the Oxalosis and Hyperoxaluria Foundation. “We’re thankful that Alnylam continues to drive forth research that may benefit the PH1 community and for conducting a study that has the potential to help those who have the most severe form of the disease.”

Results

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