- Lumasiran Resulted in Substantial Reductions in Plasma Oxalate in PH1 Patients with Severe Renal Impairment -

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today positive results from the 6-month primary analysis of the ILLUMINATE-C Phase 3 open-label study of lumasiran, an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) – the gene encoding glycolate oxidase (GO) – that is being investigated for the treatment of patients of all ages with advanced primary hyperoxaluria type 1 (PH1). The clinical data were presented at a late-breaking session at the American Society of Nephrology (ASN) Kidney Week being held as a virtual event on November 4-7. Lumasiran resulted in substantial reductions in plasma oxalate (POx) in PH1 patients with chronic kidney disease (CKD) stage 3b-5, with or without dialysis. Elevated plasma oxalate is directly correlated with the pathophysiology of systemic oxalosis, a life-threatening complication of PH1. Lumasiran demonstrated an acceptable safety profile through Month 6, with mild injection site reactions (ISRs) as the most common drug-related adverse event.

“Elevated plasma oxalate levels are responsible for much of the morbidity associated with advanced PH1 and can result in oxalosis, leading to bone fractures, cardiomyopathy, vision loss, skin ulcers and other serious manifestations,” said Mini Michael, M.D., Associate Professor, Renal Section, Department of Pediatrics, Baylor College of Medicine, Houston, and Pediatric Nephrologist, Texas Children’s Hospital. “Changes in plasma oxalate of the magnitude seen in this study are encouraging and may positively impact long-term clinical outcomes, including those related to systemic oxalosis, which will be further evaluated in the extension period of this study.”

“PH1 patients progressing to or being diagnosed with end-stage kidney disease often have substantial elevations in plasma oxalate despite intensive hemodialysis. The ILLUMINATE-C results underscore the potential of lumasiran to achieve meaningful reductions in plasma oxalate in patients with impaired kidney function, including those on hemodialysis, who are at risk of systemic oxalosis and multiorgan damage,” said Jeroen Valkenburg, General Manager, Lumasiran program at Alnylam. “We look forward to submitting these results to both the U.S. and European regulatory authorities later this year to support supplemental filings for lumasiran to allow for potential label expansions.”

Results

ILLUMINATE-C enrolled 21 patients: six patients in Cohort A who did not require dialysis and 15 patients on hemodialysis in Cohort B. The primary efficacy endpoint of the study was the percent change in POx (Cohort A) and predialysis POx (Cohort B) from baseline to Month 6, averaged across Months 3 to 6. Treatment with lumasiran in Cohorts A and B, respectively, led to 33 percent and 42 percent mean reductions in POx and predialysis POx from baseline to Month 6. Reduction in POx was evident by Month 1 and persisted through the end of the 6-month primary analysis period. Lumasiran also demonstrated positive results across secondary endpoints, including patients in Cohort B achieving substantial reductions in POx area under the curve (AUC) 0-24h between dialysis sessions from baseline to Month 6, and lumasiran demonstrating consistent reductions across all measures of urinary oxalate in Cohort A. In addition, a similar magnitude of plasma glycolate increase, an exploratory endpoint in Cohorts A and B, was observed as compared to previously completed studies in patients with relatively preserved kidney function (ILLUMINATE-A and ILLUMINATE-B), suggesting similar pharmacodynamics of lumasiran regardless of kidney function. Mild and transient ISRs were the most common drug-related AE reported in 24 percent (5/21) of patients. There were no deaths and no serious or severe AEs related to lumasiran. Furthermore, there were no treatment discontinuations or study withdrawals.

Results from a separate modeling analysis were also presented at ASN Kidney Week, predicting a long-term reduction in kidney failure risk among PH1 patients treated with lumasiran, assuming prompt treatment at diagnosis.

To view the full results presented at the virtual ASN Kidney Week, please visit www.alnylam.com/capella.

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 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