Lumasiran, sold under the brand name Oxlumo, is a medication for the treatment of primary hyperoxaluria type 1 (PH1).^[7][4][8][9]

The most common side effects include injection site reactions and abdominal pain.^[4]

Lumasiran is a double-stranded small interfering ribonucleic acid (siRNA) that reduces levels of glycolate oxidase (GO) enzyme by targeting the HAO1 messenger ribonucleic acid (mRNA) in hepatocytes through RNA interference.^[10] Decreased GO enzyme levels reduce the amount of available glyoxylate, a substrate for oxalate production.^[10] This results in reduction of urinary and plasma oxalate levels, the underlying cause of disease manifestations in people with PH1.^[10] As the GO enzyme is upstream of the deficient alanine:glyoxylate aminotransferase (AGT) enzyme that causes PH1, the mechanism of action of lumasiran is independent of the underlying AGXT gene mutation.^[10]

Lumasiran was approved for medical use in the European Union and in the United States in November 2020.^[4][5][11] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.^[12][13]

Medical uses

Lumasiran is indicated for the treatment of primary hyperoxaluria type 1 (PH1) in adults and children of all ages.^[7][8]

PH1 is a rare illness that causes the liver to produce an excessive amount of oxalate.^[7][8] Oxalate is removed by the kidneys and through the urine.^[7] In people with PH1, the extra oxalate can cause kidney stones and kidney failure.^[7][8] The extra oxalate can also build up, and damage other parts of the body, including eyes, heart, skin, and bone.^[7][8] This is called 'oxalosis'.^[7]

History

Lumasiran was evaluated by the U.S. Food and Drug Administration (FDA) in two studies of participants with PH1: a randomized, placebo-controlled trial in participants six years and older and an open-label study in participants younger than six years (NCT03681184 and NCT03905694).^[4][8] Participants ranged in age from four months to 61 years at the first dose.^[4] In the first study, 26 participants received a monthly injection of lumasiran followed by a maintenance dose every three months; 13 participants received placebo injections.^[4] Neither the patients nor the healthcare providers knew which treatment was being given until after the trial was completed.^[8] The primary endpoint was the amount of oxalate measured in the urine over 24 hours.^[4][8] In the lumasiran group, participants had, on average, a 65% reduction of oxalate in the urine, compared to an average 12% reduction in the placebo group.^[4] By the sixth month of the study, 52% of participants treated with lumasiran reached a normal 24-hour urinary oxalate level; no participants treated with the placebo did.^[4] In the second study, 16 participants younger than six years all received lumasiran.^[4] Using another measure of oxalate in the urine, the study showed, on average, a 71% decrease in urinary oxalate by the sixth month of the study.^[4] The trials were conducted at 25 centers in the United States, Europe, and the Middle East.^[8]

The FDA granted the application for lumasiran orphan drug and breakthrough therapy designations.^[4] In addition, the manufacturer received a rare pediatric disease priority review voucher.^[4] The FDA granted the approval of Oxlumo to Alnylam Pharmaceuticals, Inc.^[4]

Society and culture

Legal status

Lumasiran is available under the UK Early Access to Medicines Scheme (EAMS) as of July 2020.^[7][10][14]

On 15 October 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Oxlumo, intended for the treatment of primary hyperoxaluria type 1 (PH1).^[15][16] The applicant for this medicinal product is Alnylam Netherlands B.V.^[15]

Lumasiran was approved for medical use in the European Union and in the United States in November 2020.^[4][5][11]