View source for Vutrisiran

{{Short description|Medication}}
{{Use American English|date=June 2022}}
{{Use dmy dates|date=June 2022}}
{{Infobox drug
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| pronounce         = 
| tradename         = Amvuttra
| Drugs.com         = 
| MedlinePlus       = 
| DailyMedID        = Vutrisiran
| pregnancy_AU      = <!-- A / B1 / B2 / B3 / C / D / X -->
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| routes_of_administration = [[Subcutaneous injection|Subcutaneous]]
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| ATC_prefix        = N07
| ATC_suffix        = XX18
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| legal_AU          = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
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| legal_BR_comment  = 
| legal_CA          = Rx-only
| legal_CA_comment  = <ref>{{cite web | title=Details for: Amvuttra | website=[[Health Canada]] | date=15 December 2023 | url=https://dhpp.hpfb-dgpsa.ca/dhpp/resource/103100 | access-date=3 March 2024}}</ref><ref>{{cite web | title=Notice: Multiple additions to the Prescription Drug List (PDL) [2023-12-22] | website=[[Health Canada]] | date=22 December 2023 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/notices-changes/multiple-additions-2023-12-22.html | access-date=3 January 2024}}</ref>
| legal_DE          = <!-- Anlage I, II, III or Unscheduled -->
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| legal_UK          = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment  = 
| legal_US          = Rx-only
| legal_US_comment  = <ref name="Amvuttra FDA label">{{cite web | title=Amvuttra- vutrisiran injection | website=DailyMed | date=21 June 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8db0facb-81b6-4006-9239-27dc6409c5d3 | access-date=3 July 2022 | archive-date=3 July 2022 | archive-url=https://web.archive.org/web/20220703053841/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8db0facb-81b6-4006-9239-27dc6409c5d3 | url-status=live }}</ref>
| legal_EU          = Rx-only
| legal_EU_comment  = <ref name="Amvuttra EPAR" />
| legal_UN          = <!-- N I, II, III, IV / P I, II, III, IV -->
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| legal_status      = <!-- For countries not listed above -->

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| index2_label = as salt
| CAS_number        = 1867157-35-4
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| IUPHAR_ligand     = 
| DrugBank          = DB16699
| DrugBank2         = DBSALT003187
| ChemSpiderID      = 
| UNII              = GB4I2JI8UI
| UNII2             = 28O0WP6Z1P
| KEGG              = D11917
| KEGG2             = D11916
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| synonyms          = ALN-65492, ALN-TTRSC02

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}}

'''Vutrisiran''', sold under the brand name '''Amvuttra''', is a [[medication]] used for the treatment of the [[polyneuropathy]] of [[hereditary transthyretin-mediated amyloidosis|hereditary transthyretin-mediated (hATTR) amyloidosis]] in adults.<ref>{{cite journal | vauthors = Tamargo J, Agewall S, Borghi C, Ceconi C, Cerbai E, Dan GA, Ferdinandy P, Grove EL, Rocca B, Sulzgruber P, Semb AG, Sossalla S, Niessner A, Kaski JC, Dobrev D | display-authors = 6 | title = New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022 | journal = European Heart Journal. Cardiovascular Pharmacotherapy | volume = 9 | issue = 4 | pages = 353–370 | date = May 2023 | pmid = 37169875 | pmc = 10236523 | doi = 10.1093/ehjcvp/pvad034 | pmc-embargo-date = May 11, 2024 }}</ref><ref name="Amvuttra FDA label" /><ref name="Alnylam PR 20220613" /> It is a double stranded [[small interfering RNA]] (siRNA) (also called RNA interference, or RNAi therapeutic) that interferes with the expression of the [[transthyretin]] (TTR) gene.<ref name="Aimo_2022">{{cite journal | vauthors = Aimo A, Castiglione V, Rapezzi C, Franzini M, Panichella G, Vergaro G, Gillmore J, Fontana M, Passino C, Emdin M | display-authors = 6 | title = RNA-targeting and gene editing therapies for transthyretin amyloidosis | journal = Nature Reviews. Cardiology | volume = 19 | issue = 10 | pages = 655–667 | date = October 2022 | pmid = 35322226 | doi = 10.1038/s41569-022-00683-z | hdl = 11382/558829 | s2cid = 247623259 | url = https://discovery.ucl.ac.uk/id/eprint/10161200/ | hdl-access = free }}</ref><ref name="Keam_2022">{{cite journal | vauthors = Keam SJ | title = Vutrisiran: First Approval | journal = Drugs | volume = 82 | issue = 13 | pages = 1419–1425 | date = September 2022 | pmid = 35997942 | doi = 10.1007/s40265-022-01765-5 | s2cid = 251725617 | url = https://figshare.com/articles/online_resource/Vutrisiran_First_Approval/20409192 }}</ref> Transthyretin is a serum protein made in the liver whose major function is transport of vitamin A and thyroxine.<ref name="Luigetti_2020">{{cite journal | vauthors = Luigetti M, Romano A, Di Paolantonio A, Bisogni G, Sabatelli M | title = Diagnosis and Treatment of Hereditary Transthyretin Amyloidosis (hATTR) Polyneuropathy: Current Perspectives on Improving Patient Care | language = English | journal = Therapeutics and Clinical Risk Management | volume = 16 | pages = 109–123 | date = 2020-02-21 | pmid = 32110029 | pmc = 7041433 | doi = 10.2147/TCRM.S219979 | doi-access = free }}</ref><ref name="Al Musaimi_2023">{{cite journal | vauthors = Al Musaimi O, Al Shaer D, Albericio F, de la Torre BG | title = 2022 FDA TIDES (Peptides and Oligonucleotides) Harvest | journal = Pharmaceuticals | volume = 16 | issue = 3 | pages = 336 | date = February 2023 | pmid = 36986436 | pmc = 10056021 | doi = 10.3390/ph16030336 | doi-access = free }}</ref> 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.<ref name="Al Musaimi_2023" />

Vutrisiran was approved for medical use in the United States in June 2022,<ref name="Amvuttra FDA label" /><ref name="Alnylam PR 20220613">{{cite web | title=Alnylam Announces FDA Approval of Amvuttra (vutrisiran), an RNAi Therapeutic for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults | publisher=Alnylam | via=Business Wire | date=13 June 2022 | url=https://www.businesswire.com/news/home/20220603005487/en/Alnylam-Announces-FDA-Approval-of-AMVUTTRA%E2%84%A2-vutrisiran-an-RNAi-Therapeutic-for-the-Treatment-of-the-Polyneuropathy-of-Hereditary-Transthyretin-Mediated-Amyloidosis-in-Adults | access-date=14 June 2022 | archive-date=14 June 2022 | archive-url=https://web.archive.org/web/20220614055318/https://www.businesswire.com/news/home/20220603005487/en/Alnylam-Announces-FDA-Approval-of-AMVUTTRA%E2%84%A2-vutrisiran-an-RNAi-Therapeutic-for-the-Treatment-of-the-Polyneuropathy-of-Hereditary-Transthyretin-Mediated-Amyloidosis-in-Adults | url-status=live }}</ref> and in the European Union in September 2022.<ref name="Amvuttra EPAR" />

== Medical uses ==
Vutrisiran is [[indicated]] for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.<ref name="Amvuttra FDA label" />

== Adverse effects ==
Vutrisiran is generally well tolerated but side effects can include injection site reactions, fatigue, arthralgia, dyspnea, diarrhea and musculoskeletal pains.<ref name="Al Musaimi_2023" /><ref name="National Institute of Diabetes and Digestive and Kidney Diseases_2012" /> Vutrisiran treatment leads to decreased Vitamin A levels and supplementation at the recommended daily allowance of vitamin A is advised. Patients should be referred to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness) develop.<ref name="Keam_2022" />

== Pharmacokinetics ==
Plasma concentration profiles of vutrisiran showed rapid absorption and elimination from systemic circulation. There was a dose-proportional increase in peak plasma concentrations Cmax and a slightly greater than dose-proportional increase in AUC∞ inf and AUC last after a single subcutaneous dose across the dose range studied in the phase I trial in healthy volunteers.<ref name="Keam_2022" /><ref name="Habtemariam_2021" /> However, accumulation was not evident after repeated administration of vutrisiran 25&nbsp;mg every 3 months in patients with hATTR amyloidosis. Plasma concentrations of vutrisiran were detectable at 10 minutes after SC administration and peak plasma concentrations were seen at a median 4 h after SC administration of a 25&nbsp;mg single dose in healthy volunteers.<ref name="Keam_2022" /> Plasma half-life was (4.2–7.5 hours).<ref name="Habtemariam_2021" /> The apparent volume of distribution of vutrisiran is estimated to be 10.1 L. Vutrisiran is 80% plasma protein bound; however, plasma protein binding is concentration dependent and decreases with increasing concentrations. Vutrisiran distributes mainly to the liver after subcutaneous administration.<ref name="Keam_2022" /> The plasma clearance of siRNA is primarily influenced by ASGPR-facilitated uptake into the liver where the siRNAs are gradually metabolized by endonucleases and exonucleases to short nucleotide fragments of varying sizes.<ref name="Keam_2022" /><ref name="Habtemariam_2021" /> After a 25&nbsp;mg single dose SC vutrisiran in healthy volunteers, the median elimination half-life was 5.2 h and the median apparent clearance was 21.4 L/h. The primary pathway for excretion of vutrisiran is via the kidneys, although the fraction of renal clearance to total clearance was 15.5–27.5% after a single 5–300&nbsp;mg subcutaneous dose in healthy volunteers, indicating that renal excretion is a minor route of elimination.<ref name="Keam_2022" /> Across the dose levels tested, mean renal CLR of vutrisiran ranged from 4.45 to 5.74 L/hour (mean, 5 L/hour) after a single subcutaneous dose in healthy volunteers and the percentage of vutrisiran dose excreted unchanged in urine through 24 hours ranged between 15–25% and increased slightly with increasing dose, with a majority excreted within the first 12 hours after administration.<ref name="Keam_2022" /><ref name="Habtemariam_2021" /> Age, sex, bodyweight, race, and mild or moderate kidney impairment or mild hepatic impairment do not have clinically significant effects on vutrisiran pharmacokinetics. In vitro, vutrisiran was neither a substrate nor inhibitor of cytochrome P450 enzymes and is not expected to cause drug- drug interaction by inducing CYP enzymes. Vutrisiran is not expected to modulate drug transporter activities.<ref name="Keam_2022" />

== Mechanism of action ==
Vutrisiran is a gene silencing double-stranded siRNA-GalNAc conjugate that causes degradation of mutant and wild-type TTR mRNA through RNA interference by binding and silencing messenger RNA (mRNA) encoding for disease causing protein (Transthyretin), which results in a reduction of serum TTR protein and TTR protein deposits in tissues.<ref name="Keam_2022" /><ref>{{cite journal | vauthors =  | title = Vutrisiran Sodium | journal = American Journal of Health-System Pharmacy | volume = 79 | issue = 19 | pages = 1617–1618 | date = September 2022 | pmid = 35904362 | doi = 10.1093/ajhp/zxac195 }}</ref> Vutrisiran utilises a GalNAc conjugate delivery platform which is an enhanced stabilisation chemistry. This allows subcutaneous administration of smaller doses with longer dosing intervals.<ref name="Ioannou_2023">{{cite journal | vauthors = Ioannou A, Fontana M, Gillmore JD | title = RNA Targeting and Gene Editing Strategies for Transthyretin Amyloidosis | journal = BioDrugs | volume = 37 | issue = 2 | pages = 127–142 | date = March 2023 | pmid = 36795354 | pmc = 9933836 | doi = 10.1007/s40259-023-00577-7 }}</ref>

== History ==
The U.S. [[Food and Drug Administration]] (FDA) granted the application for vutrisiran [[orphan drug]] designation.<ref>{{cite web | title=Vutrisiran Orphan Drug Designations and Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=25 May 2018 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=637618 | access-date=14 June 2022 | archive-date=14 June 2022 | archive-url=https://web.archive.org/web/20220614055903/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=637618 | url-status=live }}</ref>

=== Efficacy and trials ===
Preclinical: In preclinical studies involving nonhuman primates, single SC doses of vutrisiran 0.3 and 1&nbsp;mg/kg achieved mean maximum TTR reductions of 55% and 96%, respectively, with serum TTR reductions persisting beyond 4 months for the 1&nbsp;mg/kg dose. In the same study, monthly doses of 1 and 3&nbsp;mg/kg maintained a reduction of TTR levels at 96%, relative to baseline. These potent and durable pharmacodynamic properties of vutrisiran, together with an acceptable safety profile, prompted further evaluation in a phase I clinical study.<ref name="Habtemariam_2021">{{cite journal | vauthors = Habtemariam BA, Karsten V, Attarwala H, Goel V, Melch M, Clausen VA, Garg P, Vaishnaw AK, Sweetser MT, Robbie GJ, Vest J | display-authors = 6 | title = Single-Dose Pharmacokinetics and Pharmacodynamics of Transthyretin Targeting N-acetylgalactosamine-Small Interfering Ribonucleic Acid Conjugate, Vutrisiran, in Healthy Subjects | journal = Clinical Pharmacology and Therapeutics | volume = 109 | issue = 2 | pages = 372–382 | date = February 2021 | pmid = 32599652 | doi = 10.1002/cpt.1974 | s2cid = 220271638 }}</ref>

Clinical trials:

A phase I clinical trial (NCT02797847) was completed in January 2018, in which vutrisiran was evaluated to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics in 80 healthy volunteers.<ref name="Habtemariam_2021" /><ref name="Zhang_2021">{{cite journal | vauthors = Zhang MM, Bahal R, Rasmussen TP, Manautou JE, Zhong XB | title = The growth of siRNA-based therapeutics: Updated clinical studies | journal = Biochemical Pharmacology | volume = 189 | pages = 114432 | date = July 2021 | pmid = 33513339 | pmc = 8187268 | doi = 10.1016/j.bcp.2021.114432 }}</ref> It was a randomized, single blind, placebo- controlled study.<ref name="Aimo_2022" /> Participants were randomized 6:2 to receive a single subcutaneous dose of vutrisiran (5 – 300&nbsp;mg) or placebo (normal saline).<ref name="Zhang_2021" /> Vutrisiran was found to be well tolerated, established a good safety profile and elicited rapid robust and durable TTR reduction.<ref name="Habtemariam_2021" /><ref name="Adams_2023">{{cite journal | vauthors = Adams D, Tournev IL, Taylor MS, Coelho T, Planté-Bordeneuve V, Berk JL, González-Duarte A, Gillmore JD, Low SC, Sekijima Y, Obici L, Chen C, Badri P, Arum SM, Vest J, Polydefkis M | display-authors = 6 | title = Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial | journal = Amyloid | volume = 30 | issue = 1 | pages = 18–26 | date = March 2023 | pmid = 35875890 | doi = 10.1080/13506129.2022.2091985 | s2cid = 251033186 | doi-access = free | hdl = 1959.4/unsworks_80922 | hdl-access = free }}</ref> Vutrisiran achieved a dose-dependent TTR knockdown; a single 25&nbsp;mg subcutaneous dose resulted in a maximum TTR reduction of 80%, which was sustained for 90 days.<ref name="Ioannou_2023" /> Based on these results, the company launched two phase III trials: HELIOS-A and HELIOS-B.<ref name="Zhang_2021" />

HELIOS-A (NCT03759379) was a phase III, global, open-label study comparing the efficacy and safety of vutrisiran to patisiran. 164 ATTRv amyloidosis patients were randomized 3:1 to subcutaneous vutrisiran 25&nbsp;mg every 3 months or patisiran 0.3&nbsp;mg/kg IV infusion every 3 weeks for 18 months’ treatment period to be followed by a lengthier extension period.<ref name="Zhang_2021" /><ref name="Adams_2023" /> The study used the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy end points.<ref name="Luigetti_2020" /> The primary endpoints of the study are the change from baseline in modified Neuropathy Impairment Score mNIS+7 and Norfolk Quality of Life-Diabetic Neuropathy QOL-DN score. Secondary endpoints include measures of mobility, BMI, disability, and serum TTR.<ref name="Zhang_2021" /> Vutrisiran met the primary endpoints at 9 months, which were maintained through 18 month.<ref name="Maurer_2022">{{cite journal | vauthors = Maurer MS | title = Overview of Current and Emerging Therapies for Amyloid Transthyretin Cardiomyopathy | journal = The American Journal of Cardiology | volume = 185 | pages = S23–S34 | date = December 2022 | issue = Suppl 1 | pmid = 36371281 | doi = 10.1016/j.amjcard.2022.10.014 | s2cid = 253476162 }}</ref> It also met all secondary efficacy endpoints.<ref name="Adams_2023" /> Additionally, patients in HELIOS-A showed improvement across exploratory cardiac end points.<ref name="Maurer_2022" /> Vutrisiran treatment resulted in rapid (≤3 weeks) and sustained reduction in serum TTR levels over 18 months, similar to what was observed in the patisiran group. Following 18 months of vutrisiran treatment, steady-state mean (SD) peak and trough serum TTR reductions from baseline were 87.6% and 81.0%, respectively. The fluctuation between median steady-state peak and trough values was lower with vutrisiran compared with patisiran, which was reflected in the reduced variability in TTR reduction (smaller standard error) observed at most time points with vutrisiran. Serum TTR reduction with vutrisiran was also similar across all patient subgroups. As expected from previous studies, serum vitamin A levels were reduced in parallel with reductions in serum TTR levels in both treatment groups.<ref name="Adams_2023" /> The extent of the reduction in TTR was not affected by TTR genotype (45.1% of participants were V30M and 54.9% had 1 of 24 other mutations), or patient age, sex, body weight or race.<ref name="Keam_2022" /> A subcutaneous dose of 25&nbsp;mg vutrisiran every 3 months caused similar or greater efficacy than patisiran given as IV infusion three times a week.<ref name="Zhang_2021" /> Vutrisiran significantly improved multiple disease-relevant outcomes versus placebo, with an acceptable safety profile.<ref name="Adams_2023" /> These findings from HELIOS-A resulted in FDA and EMA approval of vutrisiran for treatment of ATTRv-PN.<ref name="Ioannou_2023" /> The ongoing extension period of HELIOS-A will assess long-term safety and efficacy with continued Q3M vutrisiran treatment, or an alternative every 6 months dosing regimen.<ref name="Adams_2023" /> The estimated completion date is May 2024.<ref name="Yadav_2021">{{cite journal | vauthors = Yadav JD, Othee H, Chan KA, Man DC, Belliveau PP, Towle J | title = Transthyretin Amyloid Cardiomyopathy-Current and Future Therapies | journal = The Annals of Pharmacotherapy | volume = 55 | issue = 12 | pages = 1502–1514 | date = December 2021 | pmid = 33685242 | doi = 10.1177/10600280211000351 | s2cid = 232160553 }}</ref>

A study whose results are awaited is the phase III HELIOS-B (NCT04153149) randomized, double-blind, placebo-controlled trial, in which patients with TTR-related amyloid heart disease, both wild-type and mutated forms, are enrolled to evaluate the possible effects of the drug in terms of cardiac involvement.<ref name="Ioannou_2023" /><ref name="Zhang_2021" /><ref>{{cite journal | vauthors = Cantone A, Sanguettoli F, Dal Passo B, Serenelli M, Rapezzi C | title = The treatment of amyloidosis is being refined | journal = European Heart Journal Supplements | volume = 24 | issue = Suppl I | pages = I131–I138 | date = November 2022 | pmid = 36380794 | pmc = 9653129 | doi = 10.1093/eurheartjsupp/suac104 }}</ref> The estimated completion date is June 2025. Patients are randomized on a 1:1 basis to receive 25&nbsp;mg of vutrisiran or placebo administered as a subcutaneous injection once every 3 months for up to 36 months. The primary end point will evaluate the efficacy of vutrisiran in the composite outcome of reducing all-cause mortality and recurrent cardiovascular hospitalization.<ref name="Yadav_2021" /> Secondary endpoints include measures of functional exercise capacity, self-perception of health status, and cardiac structure and function.<ref name="Zhang_2021" />

=== Safety ===
Vutrisiran is well tolerated and has an acceptable safety profile. In contrast to patisiran, patients do not require premedication, although all patients require vitamin A supplementation. The majority of adverse events in the phase I trial of vutrisiran were mild, and included nasopharyngitis, headache, diarrhoea and nausea, and injection site reactions.<ref name="Ioannou_2023" /> HELIOS-A trial also reported encouraging safety and tolerability, with the majority of adverse events being mild or moderate 10 and no drug- related discontinuations or deaths occurred.<ref name="Maurer_2022" /> Only two serious adverse events were attributed to vutrisiran—dyslipidaemia and urinary tract infection.<ref name="Ioannou_2023" /> AEs occurring in (≥ 10%) of patients receiving vutrisiran included falls, pain in extremity, diarrhea, peripheral edema, urinary tract infection, arthralgia, and dizziness; all of which, except pain in extremity and arthralgia, occurred at a similar or lower rate than in the external placebo group. There were no cardiac AEs related to vutrisiran in the safety population. Five patients (4.1%) who received vutrisiran reported mild and transient injection site reactions (ISRs). There were no safety signals regarding liver function tests, haematology, or renal function related to vutrisiran. Four vutrisiran recipients (3.3%) developed antidrug antibodies (ADAs) that were low and transient with no evidence of an effect on clinical efficacy, safety, pharmacokinetics or pharmacodynamic parameters.<ref name="Adams_2023" /> No clinically significant changes in laboratory measures, vital signs, physical examinations, or electrocardiogram were noted.<ref name="Habtemariam_2021" />

== Society and culture ==
=== Legal status ===
In July 2022, 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 Amvuttra, intended for treatment of hereditary transthyretin-mediated (hATTR) amyloidosis.<ref name="Amvuttra: Pending EC decision" /> Amvuttra was designated as an orphan medicinal product on 25 May 2018.<ref name="Amvuttra: Pending EC decision" /> The applicant for this medicinal product is Alnylam Netherlands B.V.<ref name="Amvuttra: Pending EC decision">{{cite web | title=Amvuttra: Pending EC decision | website=European Medicines Agency | date=21 July 2022 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/amvuttra | access-date=30 July 2022 | archive-date=28 July 2022 | archive-url=https://web.archive.org/web/20220728170535/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/amvuttra | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Vutrisiran was approved for medical use in the European Union in September 2022.<ref name="Amvuttra EPAR">{{cite web | title=Amvuttra EPAR | website=European Medicines Agency | date=18 July 2022 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/amvuttra | access-date=13 October 2022}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{cite web | title=Amvuttra Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1681.htm | access-date=3 March 2023}}</ref> Vutrisiran is also under regulatory review for the treatment of polyneuropathy of hATTR amyloidosis in adults in Japan and Brazil, and is being investigated in amyloidosis with cardiomyopathy in the ongoing phase III, HELIOS-B trial.<ref name="Keam_2022" />

=== Names ===
Vutrisiran is the [[international nonproprietary name]] (INN).<ref>{{cite journal | vauthors = ((World Health Organization)) | year = 2019 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 81 | journal = WHO Drug Information | volume = 33 | issue = 1 | page = | hdl = 10665/330896 | hdl-access = free | author-link = World Health Organization }}</ref>

=== Formulations ===
Vutrisiran sodium is available in solution in a single-dose prefilled syringe of 25&nbsp;mg/0.5 mL under the brand name Amvuttra.<ref name="National Institute of Diabetes and Digestive and Kidney Diseases_2012">{{Cite book |url=http://www.ncbi.nlm.nih.gov/books/NBK547852/ |title=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury |date=2012 |publisher=National Institute of Diabetes and Digestive and Kidney Diseases |location=Bethesda (MD) |pmid=31643176}}</ref>

== References ==
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