Alnylam's Study on Renal Treatment Shows Promising Results In Phase III Trial
Massachusetts-based RNAi therapeutics firm Alnylam Pharmaceuticals has announced promising results from its Phase 3 trial on a potential treatment for renal decline.
ILLUMINATE-C is an open-label trial focused on lumasiran, a subcutaneously administered RNAi therapeutic targeting hydroxy acid oxidase 1 (HAO1) that's being developed to treat hyperoxaluria type 1 (PH1). The U.S. Food and Drug Administration has already given its go-ahead to use lumasiran to treat PH1 and lower the urinary oxalate levels in pediatric and adult patients under the brand name OXLUMO.
Results from the first six months of ILLUMINATE-C showed a significant reduction in plasma oxalate from baseline in patients diagnosed with advanced renal disease, including those undergoing hemodialysis. An elevated plasma oxalate is directly linked to many systemic dysfunctions that lead to cardiomyopathy, vision loss, bone fractures, impaired erythropoiesis, skin ulcers, and more. The trial demonstrated the tolerability and safety of lumasiran over the six-month period across all age profiles. No drug-related serious adverse events and injection site reactions were seen.
"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, the general manager of the Lumasiran program, in a statement.
ILLUMINATE-C is being conducted at 13 study sites across 10 countries. Cohort A enrolled six patients with advanced PH1 who do not require dialysis, while Cohort B enrolled 15 patients dependent on hemodialysis. The doses are based on the weight of each participant, and they were given three monthly starting doses, followed by monthly or quarterly doses. The researchers evaluated measures of plasma oxalate, changes in urinary oxalate, renal function, the frequency and mode of dialysis, frequency of renal stone events, and systemic oxalosis measures.
After the first six months, the researchers saw that both groups had a substantial reduction in plasma oxalates from their respective baselines. Lumasiran also showed positive results across secondary endpoints, including measures of urinary oxalate (for Cohort A patients) and additional measures of plasma oxalate.
No drug-related SAEs or deaths were logged among the enrolled participants. There were two patients whose trials were discontinued due to issues not related to the use of lumasiran, while those who reported some reactions (around 5 percent) were very mild.
The study is ongoing, and the researchers are looking forward to reporting complete data before the medical congress in 2022. Alnylam Pharmaceuticals said it plans to submit a Supplemental New Drug Application (sNDA) for lumasiran with the FDA and the Type II Variation with the European Medicines Agency (EMA) before the end of 2021.