Lumasiran

Last updated

Lumasiran
Lumasiran 02.svg
Clinical data
Trade names Oxlumo
Other namesALN-GO1
License data
Routes of
administration 		Subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG

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

Contents

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

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]

Related Research Articles

Ustekinumab, sold under the brand name Stelara among others, is a monoclonal antibody medication developed by Janssen Pharmaceuticals, for the treatment of Crohn's disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis, targeting both IL-12 and IL-23.

<span class="mw-page-title-main">Dapagliflozin</span> Diabetes medication

Dapagliflozin, sold under the brand names Farxiga (US) and Forxiga (EU) among others, is a medication used to treat type 2 diabetes. It is also used to treat adults with heart failure and chronic kidney disease. It reversibly inhibits sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.

Primary hyperoxaluria is a rare condition, resulting in increased excretion of oxalate, with oxalate stones being common.

<span class="mw-page-title-main">Dupilumab</span> Drug used to treat allergic diseases

Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody blocking interleukin 4 and interleukin 13, used for allergic diseases such as atopic dermatitis (eczema), asthma and nasal polyps which result in chronic sinusitis. It is also used for the treatment of eosinophilic esophagitis and prurigo nodularis.

<span class="mw-page-title-main">Cabotegravir</span> Medication for HIV/AIDS

Cabotegravir, sold under the brand name Vocabria among others, is a antiretroviral medication used for the treatment of HIV/AIDS. It is available in the form of tablets and as an intramuscular injection, as well as in an injectable combination with rilpivirine under the brand name Cabenuva.

Evinacumab, sold under the brand name Evkeeza, is a monoclonal antibody medication for the treatment of homozygous familial hypercholesterolemia (HoFH).

Inebilizumab, sold under the brand name Uplizna, is a medication for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults. Inebilizumab is a humanized mAb that binds to and depletes CD19+ B cells including plasmablasts and plasma cells.

<span class="mw-page-title-main">Opicapone</span> Chemical compound

Opicapone, sold under the brand name Ongentys, is a medication which is administered together with levodopa in people with Parkinson's disease. Opicapone is a catechol-O-methyltransferase (COMT) inhibitor.

<span class="mw-page-title-main">Loncastuximab tesirine</span> Medication

Loncastuximab tesirine, sold under the brand name Zynlonta, is a monoclonal antibody conjugate medication used to treat large B-cell lymphoma and high-grade B-cell lymphoma. It is an antibody-drug conjugate (ADC) composed of a humanized antibody targeting the protein CD19.

Sutimlimab, sold under the brand name Enjaymo, is a monoclonal antibody that is used to treat adults with cold agglutinin disease (CAD). It is given by intravenous infusion. Sutimlimab prevents complement-enhanced activation of autoimmune human B cells in vitro.

Givosiran, sold under the brand name Givlaari, is a medication used for the treatment of adults with acute hepatic porphyria. Givosiran is a small interfering RNA (siRNA) directed towards delta-aminolevulinate synthase 1 (ALAS1), an important enzyme in the production of heme.

<span class="mw-page-title-main">Cenobamate</span> Anticonvulsant drug

Cenobamate, sold under the brand names Xcopri (US) and Ontozry (EU), is a medication used for the treatment of partial-onset seizures, a kind of epilepsy, in adults. It is taken by mouth.

<span class="mw-page-title-main">Casirivimab/imdevimab</span> Antiviral combination medication

Casirivimab/imdevimab, sold under the brand name REGEN‑COV among others, is a combination medicine used for the treatment and prevention of COVID‑19. It consists of two human monoclonal antibodies, casirivimab and imdevimab that must be mixed together and administered as an infusion or subcutaneous injection. The combination of two antibodies is intended to prevent mutational escape. It is also available as a co-formulated product. It was developed by the American biotechnology company Regeneron Pharmaceuticals.

<span class="mw-page-title-main">Cabotegravir/rilpivirine</span> Co-packaged antiretroviral medication

Cabotegravir/rilpivirine, sold under the brand name Cabenuva, is a co-packaged antiretroviral medication for the treatment of HIV/AIDS. It contains cabotegravir and rilpivirine in a package with two separate injection vials.

<span class="mw-page-title-main">Sotrovimab</span> Monoclonal antibody

Sotrovimab, sold under the brand name Xevudy, is a human neutralizing monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2, known as SARS-CoV-2. It was developed by GlaxoSmithKline and Vir Biotechnology, Inc. Sotrovimab is designed to attach to the spike protein of SARS-CoV-2.

<span class="mw-page-title-main">Tirzepatide</span> Anti-diabetic medication

Tirzepatide, sold under the brand name Mounjaro among others, is an antidiabetic medication used for the treatment of type 2 diabetes and for weight loss. Tirzepatide is administered via subcutaneous injections.

Efgartigimod alfa, sold under the brand name Vyvgart, is a medication used to treat myasthenia gravis. Efgartigimod alfa is a neonatal Fc receptor blocker and is a new class of medication. It is an antibody fragment that binds to the neonatal Fc receptor (FcRn), preventing FcRn from recycling immunoglobulin G (IgG) back into the blood. The medication causes a reduction in overall levels of IgG, including the abnormal acetylcholine receptor (AChR) antibodies that are present in myasthenia gravis. It is also available coformulated with hyaluronidase.

Nirsevimab, sold under the brand name Beyfortus, is a human recombinant monoclonal antibody with activity against respiratory syncytial virus (RSV). It is a respiratory syncytial virus (RSV) F protein‑directed fusion inhibitor that is designed to bind to the fusion protein on the surface of the RSV virus.

Vutrisiran, sold under the brand name Amvuttra, is a medication used for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. It is a double stranded small interfering RNA (siRNA) that interferes with the expression of the transthyretin (TTR) gene. Transthyretin is a serum protein made in the liver whose major function is transport of vitamin A and thyroxine. Rare mutations in the transthyretin gene result in accumulation of large amyloid deposits of misfolded transthyretin molecules most prominently in peripheral nerves and the heart. Patients with hATTR typically present with polyneuropathy or autonomic dysfunction followed by cardiomyopathy which, if untreated, is fatal within 5 to 10 years.

Spesolimab, sold under the brand name Spevigo, is a monoclonal antibody used for the treatment of generalized pustular psoriasis (GPP). It is an interleukin-36 receptor (IL-36R) antagonist. It is given via injection into a vein.

References

  1. ↑ "Oxlumo Lumasiran Injection Product Monograph" (PDF). Alnylam Netherlands B.V. The Drug and Health Product Register, The Government of Canada. Archived (PDF) from the original on 29 June 2022. Retrieved 29 June 2022.
  2. ↑ "Summary Basis of Decision - Oxlumo". Health Canada. 23 October 2014. Retrieved 6 August 2022.
  3. ↑ "Oxlumo- lumasiran injection, solution". DailyMed. Archived from the original on 4 May 2022. Retrieved 26 December 2020.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 "FDA Approves First Drug to Treat Rare Metabolic Disorder". U.S. Food and Drug Administration (FDA) (Press release). 23 November 2020. Archived from the original on 23 November 2020. Retrieved 23 November 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  5. 1 2 3 "Oxlumo EPAR". European Medicines Agency (EMA). 13 October 2020. Archived from the original on 10 January 2021. Retrieved 26 December 2020.
  6. ↑ "Oxlumo Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  7. 1 2 3 4 5 6 7 8 "Lumasiran: Public Assessment Report (PAR)" (PDF). Medicines and Healthcare products Regulatory Agency (MHRA). Archived (PDF) from the original on 21 October 2020. Retrieved 17 October 2020. Contains public sector information licensed under the Open Government Licence v3.0.
  8. 1 2 3 4 5 6 7 8 9 "Drugs Trials Snapshot: Oxlumo". U.S. Food and Drug Administration (FDA). 23 November 2020. Archived from the original on 22 December 2020. Retrieved 26 December 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. ↑ D'Ambrosio V, Ferraro PM (2022). "Lumasiran in the Management of Patients with Primary Hyperoxaluria Type 1: From Bench to Bedside". International Journal of Nephrology and Renovascular Disease. 15: 197–206. doi: 10.2147/IJNRD.S293682 . PMC   9211742 . PMID   35747094.
  10. 1 2 3 4 5 "Lumasiran: Treatment protocol: Information for healthcare professionals" (PDF). Medicines and Healthcare products Regulatory Agency (MHRA). Archived (PDF) from the original on 19 October 2020. Retrieved 17 October 2020. Contains public sector information licensed under the Open Government Licence v3.0.
  11. 1 2 "Drug Approval Package: Oxlumo". U.S. Food and Drug Administration (FDA). 21 December 2020. Archived from the original on 22 January 2021. Retrieved 17 January 2021.
  12. ↑ "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Archived from the original on 18 January 2021. Retrieved 17 January 2021.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  13. ↑ Scott LJ, Keam SJ (February 2021). "Lumasiran: First Approval". Drugs. 81 (2): 277–282. doi:10.1007/s40265-020-01463-0. PMID   33405070. S2CID   230783803.
  14. ↑ "Alnylam Announces that the United Kingdom's MHRA Grants Early Access to Lumasiran". Alnylam Pharmaceuticals, Inc. (Press release). 13 July 2020. Archived from the original on 18 October 2020. Retrieved 17 October 2020.
  15. 1 2 "Oxlumo: Pending EC decision". European Medicines Agency (EMA). 16 October 2020. Archived from the original on 18 October 2020. Retrieved 16 October 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  16. ↑ "First treatment for rare condition primary hyperoxaluria type 1". European Medicines Agency (EMA) (Press release). 15 October 2020. Archived from the original on 18 October 2020. Retrieved 16 October 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.