Jeroen Valkenburg, General Manager of the Lumasiran program at Alnylam Pharmaceuticals, describes the results of ILLUMINATE-C, a phase 3 clinical trial evaluating the safety and efficacy of lumasiran in advanced primary hyperoxaluria type 1 (PH1) patients.
PH1 is a rare genetic condition that is often difficult to diagnose since its main symptom is the development of kidney stones. These rare type of kidney stones are formed due to the build up of oxalate, which normally is filtered through the kidneys and excreted. PH1 is due to mutations in the AGXT gene.
In November 2020, the FDA approved lumasiran for the reduction of urinary oxalate in pediatric and adult PH1 patients. The approval was based on the results of the ILLUMINATE-A and ILLUMINATE-B clinical trials, which demonstrated the drug’s safety and efficacy in lowering urinary oxalate levels in PH1 patients.
A third clinical trial, ILLUMINATE-C, is a phase 3, multi-center, single-arm, open-label trial testing lumasiran in advanced PH1 patients (i.e., PH1 patients with chronic kidney disease). As Mr. Valkenburg explains, at Kidney Week 2021, 6-month primary analysis data from the ILLUMINATE-C trial of lumasiran was presented. Overall, the results demonstrate that treatment with lumasiran led to a substantial reduction in plasma oxalate. In Cohort A, which included patients who had an Estimated Glomerular Filtration Rate (EGFR) of < 45, the mean reduction was 33%. In Cohort B, which included patients who were receiving hemodialysis, the mean reduction was 42%.
Plasma oxalate is associated with systemic oxalosis which can cause cardiomyopathy, blindness, skin ulcers, and bone fractures, and the current standard of care for patients with plasma oxalate is intensive hemodialysis which severely diminishes quality of life. The above results are thus significant as they give hope to patients with advanced PH1 who are hoping for a better treatment option.
For more information about PH1 and other kidney disorders, click here.