Alnylam Pharmaceuticals announced Tuesday that a Phase III study of the investigational RNAi therapeutic lumasiran met its main goal, significantly reducing urinary oxalate levels relative to placebo in patients with primary hyperoxaluria type 1 (PH1). The company said that based on results of the ILLUMINATE-A trial, it plans to submit marketing applications for the drug in the US and Europe in early 2020.
Akshay Vaishnaw, president of R&D, remarked that the findings "demonstrate that lumasiran can significantly reduce the hepatic production of oxalate, which we believe can thereby address the underlying pathophysiology of PH1." The therapeutic, which utilises Alnylam's enhanced stabilisation chemistry-GalNAc-conjugate technology, is designed to inhibit production of oxalate by silencing the HAO1 gene that encodes glycolate oxidase.
ILLUMINATE-A is designed to enroll approximately 30 patients with PH1 ages six years and older who were randomised to receive lumasiran or placebo, with lumasiran administered subcutaneously monthly for three months followed by quarterly maintenance doses. The study's primary endpoint was the percent change from baseline in 24-hour urinary oxalate excretion averaged across months three to six.
Alnylam said top-line data showed lumasiran met the primary endpoint and also yielded significant results for all six secondary goals, including the proportion of lumasiran-treated patients that achieved near-normalisation or normalisation of urinary oxalate levels, relative to placebo. In addition, there were no serious or severe adverse events in the study, with lumasiran having an overall safety profile comparable to that observed in previous testing. Full findings are scheduled for presentation at the OxalEurope International Congress in March.
Company president Barry Greene estimates the market opportunity for PH1 treatments to be over $500 million, while Needham analyst Alan Carr has forecast global peak sales of between $450 million and $500 million for lumasiran in 2032.
Alnylam is also conducting the Phase III ILLUMINATE-B trial of lumasiran in paediatric PH1 patients less than six years of age, with results expected in mid-2020, while findings from the late-stage ILLUMINATE-C study of lumasiran in PH1 patients of all ages with advanced renal disease are due in 2021.
The company has two other gene-silencing treatments on the market for rare hereditary disorders, including Onpattro (patisiran), which is approved in the US and Europe for polyneuropathy due to hereditary transthyretin-mediated amyloidosis, as well as Givlaari (givosiran), which was cleared by the FDA last month for hepatic porphyria.
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