Alnylam Pharmaceuticals announced Tuesday new positive results from the Phase III ILLUMINATE-C trial of lumasiran for advanced primary hyperoxaluria type 1 (PH1).
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Only a day after reporting good news of its vutrisiran for transthyretin-mediated hereditary (hATTR) amyloidosis, Alnylam Pharmaceuticals shared another RNA interference success. The company announced positive results from the Phase III ILLUMINATE-C trial of lumasiran for advanced primary hyperoxaluria type 1 (PH1).
Alnylam focuses on RNA interference (RNAi) therapeutics. RNAi is a natural cellular process that leverages small interfering RNA (siRNA) molecules that mediate RNAi, that work by silencing messenger RNA (mRNA), which encodes for disease-causing or disease pathway proteins. This results in abnormal proteins not being made.
The new results are from a six-month primary analysis period of the ILLUMINATE-C trial of lumasiran. The drug, marketed as Oxlumo and indicated for primary hyperoxaluria type 1, is an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1), the gene encoding glycolate oxidase (GO). The company previously reported that lumasiran caused substantial reductions in plasma oxalate (POx) at six months.
PH1 is an ultra-rare genetic disease affecting about one to three people per million in the U.S. and Europe. It is marked by oxalate overproduction in the liver, causing deposits of calcium oxalate crystals in the kidneys and urinary tract, which can cause recurrent kidney stones and nephrocalcinosis. It can lead to kidney damage, which makes the oxalate levels worse, which can cause an accumulation of oxalate in bones, eyes, skin, and heart, which can cause severe illness and death.
The new data suggested that lumasiran caused led to improvements in cardiac measures, nephrocalcinosis and kidney stone events. Also, some patients receiving the drug experienced improvements in their worst symptoms, including fatigue, nausea and bone pain. No patients reported that those symptoms grew worse. Alnylam presented the data at the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) International Congress in Paris, France.
“We are thrilled to be presenting preliminary data on clinical outcomes from our ILLUMINATE-C study,” said Dr. Pushkal Garg, M.D., chief medical officer at Alnylam. “We believe the reductions in plasma oxalate seen with lumasiran in this study, along with this newly reported evidence of improvements in exploratory endpoints of cardiac and kidney stone events and nephrocalcinosis, are encouraging and signal the potential to establish lumasiran as a therapeutic option across the spectrum of PH1 disease severity. We look forward to further analyzing these endpoints over a longer period of time in the ongoing extension period of up to 54 months to continue to assess the impact of treatment with lumasiran on long-term clinical outcomes, including the manifestations of systemic oxalosis.”
Monday’s news involved 18-month data from its Phase III Helios-A study. The drug improved clinical cardiac symptoms in patients with transthyretin-mediated hereditary (hATTR) amyloidosis. The data was culled from patients with pre-existing cardiac amyloid involvement, which presented as a thickened left ventricular (LV) wall thickness greater than or equal to 1.3 cm. Improvements were seen via echocardiogram parameters such as cardiac output, LV wall thickness, LV-end diastolic volume and global longitudinal strain.
hATTR can cause cardiomyopathy symptoms, gastrointestinal problems, autonomic neuropathy and/or peripheral neuropathy. The drug is designed to interfere with the production of abnormal TTR proteins, silencing the mRNA associated with the production of the proteins.
“While the full clinical significance of these findings requires further evaluation, the 18-month exploratory results from HELIOS-A continue to support the potential for vutrisiran to reduce amyloid burden in the heart and suggest that patients with a high degree of cardiac amyloid burden may benefit from this investigational RNAi therapeutic,” said Rena N. Denoncourt, vice president and TTR franchise lead at Alnylam. “We look forward to seeing data from the APOLLO-B and HELIOS-B studies, which are investigating the efficacy and safety of patisiran and vutrisiran, respectively, to treat the cardiomyopathy of wild-type and hereditary ATTR amyloidosis.”
