RARE Daily

Health Canada Authorizes Alnylam’s Oxlumo for Ultra-Rare Liver Disease

May 18, 2022

Health Canada has issued a Notice of Compliance authorizing Alnylam Pharmaceutical’s Oxlumo for the treatment of the ultra-rare liver disease primary hyperoxaluria type 1 to lower urinary oxalate levels in pediatric and adult patients.

Photo: Elizabeth Harvey, pediatric nephrologist at The Hospital for Sick Children and a member of Alnylam Canada’s Scientific Advisory Board

Primary hyperoxaluria type 1 (PH1) is characterized by oxalate overproduction. Oxalate is an end-product of metabolism and high levels of it are toxic because it cannot be broken down by the human body. Oxalate overproduction results in the deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of painful and recurrent kidney stones, nephrocalcinosis (renal deposition of calcium oxalate crystals), progression to ESKD (kidney failure), and systemic organ dysfunction.

There are several types of primary hyperoxaluria (PH), however, PH1 is the most common and the most severe form accounting for 70 to 80 percent of all PH cases. Symptom onset ranges from early infancy to sixty years of age with the median age being four to six years. The remainder of affected cases present in adulthood with 20 to 50 percent presenting late stages of chronic kidney disease when diagnosed.

The only curative treatment is a liver transplant and if the patient has already progressed to kidney failure, then a dual liver/kidney transplant is required. However, liver transplantation is associated with high morbidity and mortality, and life-long immunosuppression, leaving patients with limited options.

Oxlumo is a double-stranded siRNA that reduces the levels of the enzyme glycolate oxidase (GO) responsible for supporting the production of oxalate by targeting the hydroxy acid oxidase 1 (HAO1) messenger ribonucleic acid (mRNA) in major cells of the liver known as hepatocytes through RNA interference. As a result, decreased GO enzyme levels reduce the amount of urinary and plasma oxalate levels, the underlying cause of disease manifestations in patients with PH1.

“PH1 is a challenging condition to diagnose and treat due to significant variations in the age of onset, rate of disease progression, and associated clinical manifestations,” says Elizabeth Harvey, pediatric nephrologist at The Hospital for Sick Children and a member of Alnylam Canada’s Scientific Advisory Board. “The approval of this therapy presents patients with a novel treatment option that may potentially reduce the oxalate burden responsible for causing their disease.”

Oxlumo was granted a Notice of Compliance based on the results of a randomized, double-blind, placebo-controlled clinical study in patients six years and older with PH1 (ILLUMINATE-A) and in a single-arm clinical study in patients less than 6 years of age with PH1 (ILLUMINATE-B). The ILLUMINATE-A study showed that Oxlumo met its primary endpoint, evidenced by a 53 percent mean reduction in urinary oxalate, and a 65 percent mean reduction in urinary oxalate relative to baseline. In ILLUMINATE-B, Oxlumo demonstrated a 72 percent mean reduction in spot urinary oxalate:creatinine ratio from baseline to month six (averaged from months three to six), meeting its primary endpoint.

“This milestone is exciting, as it represents the third RNAi treatment to be brought to Canada in 3 years to treat rare and ultra-rare diseases,” says Colleen Coxson, Country General Manager, Canada, Alnylam Pharmaceuticals. “Unfortunately for many patients, it can often take years to diagnose a rare disease, and just as long to find a treatment. Bringing Oxlumo to Canadian patients with PH1 further cements Alnylam Canada’s commitment to the rare disease community.”

Author: Rare Daily Staff

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