Lumasiran, sold under the brand name Oxlumo, is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

for the treatment of

primary hyperoxaluria Primary hyperoxaluria is a rare condition (autosomal recessive), resulting in increased excretion of oxalate (up to 600 mg a day from normal 50 mg a day), with oxalate stones being common. Signs and symptoms Primary hyperoxaluria is an ...

type 1 (PH1). The most common side effects include injection site reactions and abdominal pain. 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. Decreased GO enzyme levels reduce the amount of available glyoxylate, a substrate for oxalate production. This results in reduction of urinary and plasma oxalate levels, the underlying cause of disease manifestations in people with PH1. 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. Lumasiran was approved for medical use in the European Union and in the United States in November 2020. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a pharmaceutical that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medicat ...

Medical uses

Lumasiran is indicated for the treatment of primary hyperoxaluria type 1 (PH1) in adults and children of all ages. PH1 is a rare illness that causes the liver to produce an excessive amount of

oxalate Oxalate (IUPAC: ethanedioate) is an anion with the formula C2O42−. This dianion is colorless. It occurs naturally, including in some foods. It forms a variety of salts, for example sodium oxalate (Na2C2O4), and several esters such as dimethyl o ...

. Oxalate is removed by the kidneys and through the urine. In people with PH1, the extra oxalate can cause kidney stones and kidney failure. The extra oxalate can also build up, and damage other parts of the body, including eyes, heart, skin, and bone. This is called 'oxalosis'.

History

Lumasiran was evaluated by the U.S.

(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). Participants ranged in age from four months to 61 years at the first dose. 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. Neither the patients nor the healthcare providers knew which treatment was being given until after the trial was completed. The primary endpoint was the amount of oxalate measured in the urine over 24 hours. 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. 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. In the second study, 16 participants younger than six years all received lumasiran. 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. The trials were conducted at 25 centers in the United States, Europe, and the Middle East. The FDA granted the application for lumasiran

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

and breakthrough therapy designations. In addition, the manufacturer received a rare pediatric disease priority review voucher. The FDA granted the approval of Oxlumo to Alnylam Pharmaceuticals, Inc.

Society and culture

Legal status

Lumasiran is available under the UK Early Access to Medicines Scheme (EAMS) as of July 2020. Contains public sector information licensed under the Open Government Licence v3.0. Contains public sector information licensed under the Open Government Licence v3.0. On 15 October 2020, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regarding ...

(CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(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). Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. The applicant for this medicinal product is Alnylam Netherlands B.V. Lumasiran was approved for medical use in the European Union and in the United States in November 2020.

References

External links

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