– OXLUMO Demonstrated Improvements in Nephrocalcinosis in Patients with Primary Hyperoxaluria Type 1 After 12 Months of Treatment –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--May 3, 2021-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today positive early results on clinical outcome measures from the 12-month analysis of ILLUMINATE-A Phase 3 study of OXLUMO® (lumasiran), an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) – the gene encoding glycolate oxidase (GO) – for the treatment of primary hyperoxaluria type 1 (PH1). These data were presented at the American Society of Pediatric Nephrology (ASPN)/Pediatric Academic Societies (PAS) virtual meeting being held on April 30–May 4, 2021.
As previously reported, treatment with OXLUMO significantly reduced urinary oxalate levels in infants1, children1,2 and adults2 with PH1 in the ILLUMINATE-A and ILLUMINATE-B studies. OXLUMO also demonstrated an acceptable safety profile across age groups, with injection site reactions as the most common drug-related adverse reaction. New results from ILLUMINATE-A showed that treatment with OXLUMO for 12 months was associated with evidence of improvements in nephrocalcinosis in one or both kidneys, relative to baseline.
“Nephrocalcinosis is a key indicator of disease severity in PH1,” said Jeffrey M. Saland, M.D., Professor and Chief, Pediatric Nephrology and Hypertension, Jack and Lucy Clark Department of Pediatrics, Mount Sinai Kravis Children’s Hospital, New York City and Investigator on the ILLUMINATE-A trial. “Thus, unilateral and bilateral improvements in nephrocalcinosis in some patients treated with OXLUMO are a welcome observation and are consistent with our expectation of the potential clinical impact of a sustained and substantial reduction in urinary oxalate levels.”
“We are thrilled to be presenting positive nephrocalcinosis data from our ILLUMINATE-A study,” said Pushkal Garg, M.D., Chief Medical Officer at Alnylam. “These early data provide emerging evidence demonstrating improvements in nephrocalcinosis in some patients. Notably, the majority of patients with baseline nephrocalcinosis and available ultrasounds experienced improvement, often in both kidneys, after 12 months of treatment – an encouraging sign indicating the potential of OXLUMO to improve renal outcome measures in patients with PH1. We look forward to reporting additional data later in the year.”
Results
Among 24 patients in ILLUMINATE-A who had been treated with lumasiran for 12 months and had valid renal ultrasounds at baseline, 46 percent (11/24) of patients experienced improvement in nephrocalcinosis grade relative to baseline, 17 percent (4/24) remained stable, and 13 percent (3/24) experienced worsening; 25 percent (6/24) did not have ultrasounds available at 12 months. Of 14 patients with baseline nephrocalcinosis and available ultrasounds, 79 percent (11/14) showed improvement relative to baseline, and of those who improved, 73 percent (8/11) improved in both kidneys. Additional data were presented regarding effects on estimated glomerular filtration rate (eGFR) and kidney stone events.
To view the full results presented at the virtual ASPN congress, please visit www.alnylam.com/capella.
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 Prescribing Information.
About OXLUMO® (lumasiran)
OXLUMO is an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels in pediatric and adult patients. HAO1 encodes glycolate oxidase (GO), an enzyme upstream of the disease-causing defect in PH1. OXLUMO works by degrading HAO1 messenger RNA and reducing the synthesis of GO, which inhibits hepatic production of oxalate – the toxic metabolite responsible for the clinical manifestations of PH1. In the pivotal ILLUMINATE-A study, OXLUMO was shown to significantly reduce levels of urinary oxalate relative to placebo, with the majority of patients reaching normal or near-normal levels. Injection site reactions (ISRs) were the most common drug-related adverse reaction. In the ILLUMINATE-B pediatric Phase 3 study, OXLUMO demonstrated an efficacy and safety profile consistent with that observed in ILLUMINATE-A. OXLUMO utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc conjugate technology designed to increase potency and durability. OXLUMO is administered via subcutaneous injection once monthly for three months, then once quarterly thereafter at a dose based on actual body weight. For patients who weigh less than 10 kg, ongoing dosing remains monthly. OXLUMO should be administered by a healthcare professional. For more information about OXLUMO, visit OXLUMO.com.
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).
