RARE Daily

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

November 19, 2020

Rare Daily Staff

The European Commission granted marketing authorization to Alnylam Pharmaceuticals’ Oxlumo for the treatment of primary hyperoxaluria type 1 in all age groups.

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.

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.

“Prior to now there have been no approved treatment options for PH1 in Europe, so this is a potentially life-changing milestone for people diagnosed with this ultra-rare, debilitating disease—many of whom are infants and children – and their families. Lumasiran [Olxumo] will address the urgent unmet need that exists for patients with PH1 and its approval today marks our continued commitment to rare disease communities,” said John Maraganore, CEO of Alnylam.

European Union approval is based on efficacy and safety findings from both the ILLUMINATE-A and ILLUMINATE-B phase 3 studies of lumasiran. In the ILLUMINATE-A study conducted in adults and children six years or older, lumasiran achieved the primary endpoint with a 53 percent mean reduction in urinary oxalate relative to placebo and showed a 65 percent mean reduction in urinary oxalate relative to baseline. Eighty-four percent of patients achieved normal or near-normal levels of urinary oxalate and more than half of patients reached normalization, compared to zero percent in the placebo group.

In the ILLUMINATE-B phase 3 study, the efficacy results and safety profile of lumasiran in infants and children under the age of six years were found to be similar to those observed in ILLUMINATE-A.

“PH1 affects patients of all ages. It is particularly devastating when infants are born with the condition and develop kidney failure within the first few months of life,” said Sally-Anne Hulton, consultant pediatric nephrologist, Birmingham Women’s and Children’s Hospital NHS Trust, UK. “The data show meaningful and sustained reductions in urinary and plasma oxalate with an encouraging safety and tolerability profile, providing us with hope for improving care for these patients.”

Alnylam says it intends to work with health authorities across Europe to achieve responsible and sustainable access arrangements for lumasiran that address the diverse patient population affected by PH1 to ensure that all patients in need have access to lumasiran.

Lumasiran was granted Priority Medicines (PRIME) designation by the EMA as well as Orphan designation in the European Union. Lumasiran was also granted an Accelerated Assessment by the EMA, which is awarded to medicines deemed to be of major public health interest and therapeutic innovation and is designed to bring new treatments to patients more quickly. Alnylam has filed a New Drug Application with the U.S. Food and Drug Administration and has granted Priority Review with an action date of December 3, 2020 under the Prescription Drug User Fee Act (PDUFA).

Photo: John Maraganore, CEO of Alnylam


Stay Connected

Sign up for updates straight to your inbox.