FDA Clears First Drug to Treat Ultra-Rare Metabolic Disorder

Megan Brooks


November 24, 2020

The US Food and Drug Administration (FDA) has approved lumasiran (Oxlumo, Alnylam Pharmaceuticals) subcutaneous injection to treat children and adults with primary hyperoxaluria type 1 (PH1), an ultra-rare genetic disorder that causes recurrent kidney stones and loss of kidney function.

"The approval of Oxlumo represents a great triumph of community involvement to address a rare disease. It is a result of input from patients, treating physicians, experts, and sponsors at a patient-focused drug development meeting and through other collaborative efforts," Norman Stockbridge, MD, PhD, director, Division of Cardiology and Nephrology, FDA Center for Drug Evaluation and Research, said in a news release.

PH1 is the most common and severe type of primary hyperoxaluria (PH). PH1 affects an estimated 1 to 3 people per million in North America and Europe and accounts for approximately 80% of PH cases.

PH1 is characterized by oxalate overproduction, which results in deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of painful and recurrent kidney stones, nephrocalcinosis, progression to kidney failure, and systemic organ dysfunction. Lumasiran is a gene-silencing therapy that decreases oxalate production.

Studies in Those Aged 6 and Older

The drug was tested in two studies in patients with PH1. One study involved 39 patients aged 6 years and older; 26 received a monthly injection of lumasiran followed by a maintenance dose every 3 months and 13 received placebo injections. The primary endpoint was the amount of oxalate in urine over 24 hours.

Patients in the lumasiran group had an average reduction of oxalate in urine of 65%, compared with a 12% reduction in the placebo group. By month 6, 52% of patients treated with lumasiran reached a normal 24-hour urinary oxalate level versus no patients in the placebo group.

The other study was open-label and involved 16 patients younger than aged 6 years who all received lumasiran. Treatment led to an average 71% decrease in urinary oxalate by month 6.

The most common side effects of lumasiran include injection site reaction and abdominal pain.

Lumasiran for PH1 had breakthrough therapy designation, orphan drug status, and priority review status.

The manufacturer expects Oxlumo to be available for shipment to healthcare providers in the United States by year end.

Health care providers can initiate the process now by visiting www.AlnylamAssist.com and completing and submitting a start form. 

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