Lumasiran

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Lumasiran
Names
Trade namesOxlumo
Other namesALN-GO1, lumasiran sodium
Clinical data
Main usesPrimary hyperoxaluria type 1 (PH1)[1]
Side effectsInjection site reactions[1][2]
Routes of
use
Subcutaneous
Typical dose3 to 6 mg/kg[1]
External links
AHFS/Drugs.comMonograph
US NLMLumasiran
Legal
License data
Legal status

Lumasiran, sold under the brand name Oxlumo, is a medication used to treat primary hyperoxaluria type 1 (PH1).[1] It lowers both urine and blood oxalate level.[1] It is given by injection under the skin.[1]

Common side effects include injection site reactions including redness, pain, and itching.[1][2] While there is no evidence of harm in pregnancy, such use has not been well studied.[1] It is a small interfering ribonucleic acid (siRNA) that blocks HAO1 messenger ribonucleic acid (mRNA) and thus the creation of hydroxyacid oxidase.[1][2]

Lumasiran was approved for medical use in Europe and the United States in 2020.[1][2] In the United States it costs about 60,000 USD for a 94.5 mg vial as of 2022.[6]

Medical uses

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

It decreases levels of oxalate in the urine by about 65% compared to 12% seen with placebo.[2] After 6 months about 84% have normal levels while none do with placebo.[2]

Dosage

For those who weight less than 10 kg it is given at a dose of 6 mg/kg once a month for three months, than 3 mg/kg once per month.[1]

For those who weight 10 to 20 kg it is given at 6 mg/kg once a month for three months, than this dose is given every 3 months.[1]

For those who weight more than 20 kg it is given at a dose of 3 mg/kg once a month for three months, than this dose is given every 3 months.[1]

Mechanism of action

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.[9] Decreased GO enzyme levels reduce the amount of available glyoxylate, a substrate for oxalate production.[9] This results in reduction of urinary and plasma oxalate levels, the underlying cause of disease manifestations in people with PH1.[9] 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.[9]

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).[5][8] Participants ranged in age from four months to 61 years at the first dose.[5] 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.[5] 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.[5][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.[5] 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.[5] In the second study, 16 participants younger than six years all received lumasiran.[5] 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.[5] 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.[5] In addition, the manufacturer received a rare pediatric disease priority review voucher.[5] The FDA granted the approval of Oxlumo to Alnylam Pharmaceuticals, Inc.[5] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[10][11]

Society and culture

Legal status

Lumasiran is available under the UK Early Access to Medicines Scheme (EAMS) as of July 2020.[7][9][12]

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).[13][14] The applicant for this medicinal product is Alnylam Netherlands B.V.[13]

Lumasiran was approved for medical use in the European Union and in the United States in November 2020.[5][2][15]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 "Oxlumo- lumasiran injection, solution". DailyMed. Archived from the original on 4 May 2022. Retrieved 26 December 2020.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Oxlumo EPAR". European Medicines Agency (EMA). Archived from the original on 10 January 2021. Retrieved 26 December 2020.
  3. "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.
  4. "Summary Basis of Decision - Oxlumo". Health Canada. 23 October 2014. Archived from the original on 6 August 2022. Retrieved 6 August 2022.
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 "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. Public Domain This article incorporates text from this source, which is in the public domain.
  6. "Oxlumo Prices, Coupons, Copay & Patient Assistance". Drugs.com. Archived from the original on 19 January 2022. Retrieved 3 November 2022.
  7. 7.0 7.1 7.2 7.3 7.4 7.5 7.6 "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. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 "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. Public Domain This article incorporates text from this source, which is in the public domain.
  9. 9.0 9.1 9.2 9.3 9.4 "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.
  10. "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. Public Domain This article incorporates text from this source, which is in the public domain.
  11. 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.
  12. "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.
  13. 13.0 13.1 "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.
  14. "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.
  15. "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.

External links

External sites:
Identifiers:
  • 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