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 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]
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]
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]
"Lumasiran". Drug Information Portal. U.S. National Library of Medicine.
Clinical trial number NCT03681184 for "A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1 (ILLUMINATE-A)" at ClinicalTrials.gov
Clinical trial number NCT03681184 for "A Study of Lumasiran in Infants and Young Children With Primary Hyperoxaluria Type 1 (ILLUMINATE-B)" at ClinicalTrials.gov
This article incorporates text from this source, which is in the public domain.
