RARE Daily

FDA Approves Alnylam’s Oxlumo for the Treatment of Primary Hyperoxaluria Type 1

November 24, 2020

Rare Daily Staff

The U.S. Food and Drug Administration approved Alnylam Pharmaceuticals’ Oxlumo for the treatment of primary hyperoxaluria type 1 in all age groups, days after European regulators approved the drug.

Primary hyperoxaluria type 1 (PH1) is an ultra-rare orphan disease characterized by excessive oxalate production, which can lead to life threatening end-stage renal disease and other systemic complications. Heterogeneity in disease manifestation often contributes to delays in diagnosis—particularly in adult PH1 patients, with a median time from symptoms onset to diagnosis of approximately six years. Untreated PH1 leads to progressive kidney damage; patients with advanced kidney disease require intensive dialysis to help filter waste products, including oxalate, from their blood until they are able and eligible to receive a dual or sequential liver/kidney transplant, an invasive procedure associated with a high risk of morbidity and mortality, and life-long immunosuppression.

“Many people impacted by PH1 face persistent anxiety related to the unpredictable nature of their condition, in terms of the uncertainty of how quickly their disease may progress, and the prospect of needing intensive dialysis and a kidney/liver transplant that threaten their physical, emotional and financial health,” said Kim Hollander, executive director of the Oxalosis and Hyperoxaluria Foundation. “The FDA approval of Oxlumo represents a new path forward for many, providing an effective treatment option and a sense of hope.”

Oxlumo (Lumasiran) is an RNAi therapeutic targeting the hydroxyacid oxidase 1 (HAO1) mRNA that encodes glycolate oxidase (GO) – an enzyme upstream of the disease-causing defect in PH1. By degrading the HAO1 mRNA and reducing the synthesis of GO, lumasiran stops the production of oxalate – the toxic metabolite that directly contributes to the clinical manifestations of PH1.

The FDA approval of Oxlumo was primarily based on positive results from the randomized, double-blind, placebo-controlled ILLUMINATE-A phase 3 study in 39 patients with PH1, in which Oxlumo was shown to significantly reduce levels of urinary oxalate relative to placebo, with the majority of patients achieving normal or near-normal levels. Specifically, treatment with Oxlumo resulted in a 65 percent mean reduction in urinary oxalate relative to baseline versus 12 percent reduction reported in response to placebo, resulting in a mean treatment difference of 53 percent relative to placebo. Oxlumo demonstrated an encouraging safety and tolerability profile, with injection site reactions as the most common drug-related adverse reaction.

The FDA also took into consideration positive interim results from the single-arm, open-label ILLUMINATE-B phase 3 pediatric study that demonstrated the safety and efficacy of Oxlumo in patients under the age of six, and results showed reduction of urinary oxalate and an overall safety and tolerability profile consistent with that demonstrated in ILLUMINATE-A.

“The approval of OXLUMO is a further testament to the impact RNAi therapeutics can have in transforming the treatment of severe, life-threatening diseases like PH1,” said Akshay Vaishnaw, president of R&D at Alnylam. “OXLUMO marks our third FDA approval in less than three years, positioning us to meet or exceed our Alnylam 2020 strategy and goals, and further highlighting the productivity of our RNAi platform and the speed at which we can bring innovative medicines to patients.”

Oxlumo is expected to be available for shipment to healthcare providers in the U.S. by year-end. OXLUMO was reviewed by the FDA under Priority Review and had previously been granted Breakthrough Therapy, Orphan Drug, and Rare Pediatric Disease designations. With its approval, the FDA has granted Alnylam a pediatric rare disease priority review voucher that entitles the company to designate a single new drug application to qualify for a priority review in the future.

Photo: Akshay Vaishnaw, president of R&D at Alnylam


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