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{{Short description |Antiviral drug}}
{{Use dmy dates|date=December 2021}}
{{Use dmy dates|date=December 2021}}
{{Infobox drug
{{Infobox drug
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| Watchedfields = changed
| Watchedfields = changed
| verifiedrevid = 450846483
| verifiedrevid = 450846483
| type = <!-- empty -->
| image = Maribavir.svg
| image = Maribavir.svg
| width =
| width =
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<!-- Clinical data -->
<!-- Clinical data -->
| tradename = Livtencity
| tradename = Livtencity
| Drugs.com =
| Drugs.com = {{drugs.com|monograph|maribavir}}
| MedlinePlus =
| MedlinePlus =
| licence_EU = <!-- EMA uses INN (or special INN_EMA) -->
| DailyMedID = Maribavir
| DailyMedID = Maribavir
⚫
| pregnancy_AU = D
| licence_US = <!-- FDA may use generic or brand name (generic name preferred) -->
| pregnancy_AU_comment = <ref name="Livtencity APMDS" /><ref>{{cite web | title=Updates to the Prescribing Medicines in Pregnancy database | website=Therapeutic Goods Administration (TGA) | date=21 December 2022 | url=https://www.tga.gov.au/resources/resource/guidance/updates-prescribing-medicines-pregnancy-database | access-date=2 January 2023 | archive-date=3 April 2022 | archive-url=https://web.archive.org/web/20220403064059/https://www.tga.gov.au/updates-prescribing-medicines-pregnancy-database | url-status=live }}</ref>
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment =
| pregnancy_category=
| pregnancy_category=
| routes_of_administration = [[Oral administration|By mouth]]
| routes_of_administration = [[Oral administration|By mouth]]
| class =
| class =
⚫
| ATCvet =
| ATC_prefix = J05
| ATC_prefix = J05
| ATC_suffix = AX10
| ATC_suffix = AX10
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<!-- Legal status -->
<!-- Legal status -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU = S4
| legal_AU_comment = <ref name="Livtencity APMDS">{{cite web | title=Livtencity | website=Therapeutic Goods Administration (TGA) | date=21 October 2022 | url=https://www.tga.gov.au/resources/auspmd/livtencity | access-date=29 April 2023 | archive-date=5 February 2023 | archive-url=https://web.archive.org/web/20230205203443/https://www.tga.gov.au/resources/auspmd/livtencity | url-status=live }}</ref><ref>{{cite web | title=LIVTENCITY (Takeda Pharmaceuticals Australia Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=11 November 2022 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/livtencity-takeda-pharmaceuticals-australia-pty-ltd | access-date=29 April 2023 | archive-date=27 March 2023 | archive-url=https://web.archive.org/web/20230327062506/https://www.tga.gov.au/resources/prescription-medicines-registrations/livtencity-takeda-pharmaceuticals-australia-pty-ltd | url-status=live }}</ref><ref>{{cite web | title=Therapeutic Goods (Poisons Standard—June 2024) Instrument 2024 | website=Federal Register of Legislation | date=30 May 2024 | url=https://www.legislation.gov.au/F2024L00589/asmade/text | access-date=10 June 2024}}</ref>
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title = Livtencity (Maribavir tablets) Product Monograph | website=[[Health Canada]] | date = September 2022 | url = https://pdf.hres.ca/dpd_pm/00067349.PDF | access-date = 29 April 2023 | archive-date = 1 October 2022 | archive-url = https://web.archive.org/web/20221001051134/https://pdf.hres.ca/dpd_pm/00067349.PDF | url-status = live }}</ref><ref>{{cite web | title=Livtencity Summary Basis of Decision | website=[[Health Canada]] | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?lang=en&linkID=SBD00625&lang=en | access-date=10 March 2023 | archive-date=29 April 2023 | archive-url=https://web.archive.org/web/20230429042815/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?lang=en&linkID=SBD00625&lang=en | url-status=live }}</ref><ref>{{cite web | title=Details for: Livtencity | website=[[Health Canada]] | date=25 October 2022 | url=https://dhpp.hpfb-dgpsa.ca/dhpp/resource/101989 | access-date=3 March 2024 | archive-date=3 March 2024 | archive-url=https://web.archive.org/web/20240303064142/https://dhpp.hpfb-dgpsa.ca/dhpp/resource/101989 | url-status=live }}</ref>
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_DE_comment =
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| legal_UK_comment =
| legal_UK_comment =
| legal_US = Rx-only
| legal_US = Rx-only
| legal_US_comment = <ref name="Livtencity FDA label">{{cite web | title=Livtencity- maribavir tablet, coated | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c94fc2c5-e840-4f18-b7d8-d5eacb26d3a0 | access-date=19 December 2021}}</ref><ref name="FDA PR 20211123" />
| legal_US_comment = <ref name="Livtencity FDA label">{{cite web | title=Livtencity- maribavir tablet, coated | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c94fc2c5-e840-4f18-b7d8-d5eacb26d3a0 | access-date=19 December 2021 | archive-date=19 December 2021 | archive-url=https://web.archive.org/web/20211219212750/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c94fc2c5-e840-4f18-b7d8-d5eacb26d3a0 | url-status=live }}</ref><ref name="FDA PR 20211123" />
| legal_EU =
| legal_EU = Rx-only
| legal_EU_comment =
| legal_EU_comment = <ref name="Livtencity EPAR" />
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_UN_comment =
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}}
}}


'''Maribavir''', sold under the brand name '''Livtencity''', is an [[antiviral medication]] that is used to treat post-transplant [[cytomegalovirus]] (CMV).<ref name="Livtencity FDA label" /><ref name="FDA PR 20211123">{{cite press release | title=FDA Approves First Treatment for Common Type of Post-Transplant Infection that is Resistant to Other Drugs | website=U.S. [[Food and Drug Administration]] (FDA) | date=23 November 2021 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-common-type-post-transplant-infection-resistant-other-drugs | access-date=23 November 2021}} {{PD-notice}}</ref>
'''Maribavir''', sold under the brand name '''Livtencity''', is an [[antiviral medication]] that is used to treat post-transplant [[cytomegalovirus]] (CMV).<ref name="Livtencity FDA label" /><ref name="FDA PR 20211123">{{cite press release | title=FDA Approves First Treatment for Common Type of Post-Transplant Infection that is Resistant to Other Drugs | website=U.S. [[Food and Drug Administration]] (FDA) | date=23 November 2021 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-common-type-post-transplant-infection-resistant-other-drugs | access-date=23 November 2021 | archive-date=24 November 2021 | archive-url=https://web.archive.org/web/20211124015049/https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-common-type-post-transplant-infection-resistant-other-drugs | url-status=live }} {{PD-notice}}</ref> Maribavir is a cytomegalovirus pUL97 kinase inhibitor that works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication.<ref name="FDA PR 20211123" />


The most common side effects include taste disturbance, nausea, diarrhea, vomiting and fatigue.<ref name="FDA PR 20211123" />
The most common side effects include taste disturbance, nausea, diarrhea, vomiting and fatigue.<ref name="FDA PR 20211123" />


⚫
Maribavir was approved for medical use in the United States in November 2021,<ref name="FDA PR 20211123" /><ref name="Takeda PR">{{cite press release | title=Takeda's Livtencity (maribavir) Approved by U.S. FDA as the First and Only Treatment for People Ages 12 and Older with Post-Transplant Cytomegalovirus (CMV), Refractory (With or Without Genotypic Resistance) to Conventional Antiviral Therapies | website=Takeda | date=23 November 2021 | url=https://www.takeda.com/newsroom/newsreleases/2021/takeda-livtencity-maribavir-approved-by-us-fda/ | access-date=26 November 2021 | archive-date=27 November 2021 | archive-url=https://web.archive.org/web/20211127043919/https://www.takeda.com/newsroom/newsreleases/2021/takeda-livtencity-maribavir-approved-by-us-fda/ | url-status=live }}</ref> and in the European Union in November 2022.<ref name="Livtencity EPAR" /> The US [[Food and Drug Administration]] (FDA) considers it to be a [[first-in-class medication]].<ref name="New Drug Therapy Approvals 2021">{{cite report | title=Advancing Health Through Innovation: New Drug Therapy Approvals 2021 | website=U.S. [[Food and Drug Administration]] (FDA) | date=13 May 2022 | url=https://www.fda.gov/media/155227/download | format=PDF | access-date=22 January 2023 | archive-date=6 December 2022 | archive-url=https://web.archive.org/web/20221206210020/https://www.fda.gov/media/155227/download | url-status=live }} {{PD-notice}}</ref>
Maribavir is a cytomegalovirus pUL97 kinase inhibitor that works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication.<ref name="FDA PR 20211123" />

⚫
Maribavir was approved for medical use in the United States in November 2021.<ref name="FDA PR 20211123" /><ref name="Takeda PR">{{cite press release | title=Takeda's Livtencity (maribavir) Approved by U.S. FDA as the First and Only Treatment for People Ages 12 and Older with Post-Transplant Cytomegalovirus (CMV), Refractory (With or Without Genotypic Resistance) to Conventional Antiviral Therapies | website=Takeda | date=23 November 2021 | url=https://www.takeda.com/newsroom/newsreleases/2021/takeda-livtencity-maribavir-approved-by-us-fda/ | access-date=26 November 2021}}</ref>


== Medical uses ==
== Medical uses ==
Maribavir is [[Indication (medicine)|indicated]] to treat people twelve years of age and older and weighing at least {{convert|35|kg|lb}} with post-transplant cytomegalovirus infection/disease that does not respond (with or without genetic mutations that cause resistance) to available antiviral treatment for cytomegalovirus.<ref name="FDA PR 20211123" />
In the United States, maribavir is [[Indication (medicine)|indicated]] to treat people twelve years of age and older and weighing at least {{convert|35|kg|lb}} with post-transplant cytomegalovirus infection/disease that does not respond (with or without genetic mutations that cause resistance) to available antiviral treatment for cytomegalovirus.<ref name="FDA PR 20211123" />

In the European Union, maribavir is indicated for the treatment of cytomegalovirus (CMV) infection and/or disease that are refractory (with or without resistance) to one or more prior therapies, including [[ganciclovir]], [[valganciclovir]], [[cidofovir]] or [[foscarnet]] in adults who have undergone a [[hematopoietic stem cell transplant]] (HSCT) or [[Organ transplantation|solid organ transplant]] (SOT).<ref name="Livtencity EPAR" />


== Adverse effects ==
== Adverse effects ==
Adverse effects of maribavir include taste disturbances, nausea, and vomiting.<ref>{{cite journal | vauthors = Winston DJ, Young JA, Pullarkat V, Papanicolaou GA, Vij R, Vance E, Alangaden GJ, Chemaly RF, Petersen F, Chao N, Klein J, Sprague K, Villano SA, Boeckh M | display-authors = 6 | title = Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study | journal = Blood | volume = 111 | issue = 11 | pages = 5403–5410 | date = June 2008 | pmid = 18285548 | pmc = 5726327 | doi = 10.1182/blood-2007-11-121558 }}</ref>
Maribavir use can cause taste disturbances, nausea, and vomiting.


== Contraindications ==
== Contraindications ==
Maribavir may reduce the antiviral activity of [[ganciclovir]] and [[valganciclovir]], so coadministration with these medications is not recommended.<ref name="FDA PR 20211123" />
The cytomegalovirus pUL97 kinase activates [[ganciclovir]] and [[valganciclovir]], so coadministration with these medications is not recommended because maribavir may reduce their antiviral activity.<ref name="FDA PR 20211123" />


== History ==
== History ==
Maribavir is licensed by [[ViroPharma]] from [[GlaxoSmithKline]] in 2003, for the [[Prophylaxis|prevention]] and treatment of human [[cytomegalovirus]] (HCMV) disease in [[hematopoietic stem cell]]/[[bone marrow transplant]] patients. The mechanism by which maribavir inhibits HCMV replication is by inhibition of an HCMV encoded [[protein kinase]] [[enzyme]] called [[UL97]] or [[pUL97]].<ref>{{cite journal | vauthors = Biron KK, Harvey RJ, Chamberlain SC, Good SS, Smith AA, Davis MG, Talarico CL, Miller WH, Ferris R, Dornsife RE, Stanat SC, Drach JC, Townsend LB, Koszalka GW | display-authors = 6 | title = Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action | journal = Antimicrobial Agents and Chemotherapy | volume = 46 | issue = 8 | pages = 2365–72 | date = August 2002 | pmid = 12121906 | pmc = 127361 | doi = 10.1128/aac.46.8.2365-2372.2002 | author5 = Smith III AA | last7 = Talarico | last6 = Davis | last9 = Ferris | last8 = Miller | last14 = Koszalka | last11 = Stanat | last10 = Dornsife | last13 = Townsend | last12 = Drach | first8 = W. H. | first9 = R. | first6 = M. G. | first7 = C. L. | first12 = J. C. | first13 = L. B. | first10 = R. E. | first11 = S. C. | first14 = G. W. }}</ref><ref>{{Cite journal|last=Prichard|first=Mark N.|date=11 May 2009|title=Function of human cytomegalovirus UL97 kinase in viral infection and its inhibition by maribavir|journal=Reviews in Medical Virology|volume=19|issue=4|pages=215–229|doi=10.1002/rmv.615|issn=1052-9276|pmc=3777615|pmid=19434630}}</ref> Maribavir showed promise in [[clinical trial#Phase II|Phase II]] clinical trials and was granted [[FDA Fast Track Development Program|fast track]] status, but failed to meet study goals in a Phase III trial.<ref>{{cite journal | vauthors = Marty FM, Ljungman P, Papanicolaou GA, Winston DJ, Chemaly RF, Strasfeld L, Young JA, Rodriguez T, Maertens J, Schmitt M, Einsele H, Ferrant A, Lipton JH, Villano SA, Chen H, Boeckh M | display-authors = 6 | title = Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial | journal = The Lancet. Infectious Diseases | volume = 11 | issue = 4 | pages = 284–92 | date = April 2011 | pmid = 21414843 | doi = 10.1016/S1473-3099(11)70024-X }}</ref> However, the dosage used in the Phase III trial may have been too low to be efficacious.<ref>{{cite journal | vauthors = Snydman DR | title = Why did maribavir fail in stem-cell transplants? | journal = The Lancet. Infectious Diseases | volume = 11 | issue = 4 | pages = 255–7 | date = April 2011 | pmid = 21414844 | doi = 10.1016/S1473-3099(11)70033-0 }}</ref>
Maribavir is licensed by [[ViroPharma]] from [[GlaxoSmithKline]] in 2003, for the [[Prophylaxis|prevention]] and treatment of human [[cytomegalovirus]] (HCMV) disease in [[hematopoietic stem cell]]/[[bone marrow transplant]] patients. The mechanism by which maribavir inhibits HCMV replication is by inhibition of an HCMV encoded [[protein kinase]] [[enzyme]] called [[UL97]] or [[pUL97]].<ref>{{cite journal | vauthors = Biron KK, Harvey RJ, Chamberlain SC, Good SS, Smith III AA, Davis MG, Talarico CL, Miller WH, Ferris R, Dornsife RE, Stanat SC, Drach JC, Townsend LB, Koszalka GW | display-authors = 6 | title = Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action | journal = Antimicrobial Agents and Chemotherapy | volume = 46 | issue = 8 | pages = 2365–2372 | date = August 2002 | pmid = 12121906 | pmc = 127361 | doi = 10.1128/aac.46.8.2365-2372.2002 }}</ref><ref>{{cite journal | vauthors = Prichard MN | title = Function of human cytomegalovirus UL97 kinase in viral infection and its inhibition by maribavir | journal = Reviews in Medical Virology | volume = 19 | issue = 4 | pages = 215–229 | date = July 2009 | pmid = 19434630 | pmc = 3777615 | doi = 10.1002/rmv.615 }}</ref> Maribavir showed promise in [[clinical trial#Phase II|phase II]] clinical trials and was granted [[FDA Fast Track Development Program|fast track]] status, but failed to meet study goals in a phase III trial.<ref>{{cite journal | vauthors = Marty FM, Ljungman P, Papanicolaou GA, Winston DJ, Chemaly RF, Strasfeld L, Young JA, Rodriguez T, Maertens J, Schmitt M, Einsele H, Ferrant A, Lipton JH, Villano SA, Chen H, Boeckh M | display-authors = 6 | title = Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial | journal = The Lancet. Infectious Diseases | volume = 11 | issue = 4 | pages = 284–292 | date = April 2011 | pmid = 21414843 | doi = 10.1016/S1473-3099(11)70024-X }}</ref> However, the dosage used in the phase III trial may have been too low to be efficacious.<ref>{{cite journal | vauthors = Snydman DR | title = Why did maribavir fail in stem-cell transplants? | journal = The Lancet. Infectious Diseases | volume = 11 | issue = 4 | pages = 255–257 | date = April 2011 | pmid = 21414844 | doi = 10.1016/S1473-3099(11)70033-0 }}</ref>

⚫
A phase II study with maribavir demonstrated that [[prophylaxis]] with maribavir displayed strong antiviral activity, as measured by [[statistically significant]] reduction in the rate of reactivation of CMV in recipients of [[hematopoietic stem cell]]/[[bone marrow transplant]]s.<ref>{{cite press release | title=Phase 2 Data Shows Maribavir Markedly Reduced Rate Of Cytomegalovirus Infection And Disease In Bone Marrow Transplant Patients | publisher=ViroPharma | via=Medical News Today | date=30 August 2008 | url=http://www.medicalnewstoday.com/articles/109557.php | archive-url=https://web.archive.org/web/20090103195326/http://www.medicalnewstoday.com/articles/109557.php | archive-date=3 January 2009 | url-status=dead | access-date=25 November 2022}}</ref> In an [[intent-to-treat]] analysis of the first 100 days after the transplant, the number of subjects who required pre-emptive anti-CMV therapy was statistically significantly reduced with maribavir compared to placebo.<ref>{{cite journal | vauthors = Winston DJ, Young JA, Pullarkat V, Papanicolaou GA, Vij R, Vance E, Alangaden GJ, Chemaly RF, Petersen F, Chao N, Klein J, Sprague K, Villano SA, Boeckh M | display-authors = 6 | title = Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study | journal = Blood | volume = 111 | issue = 11 | pages = 5403–5410 | date = June 2008 | pmid = 18285548 | pmc = 5726327 | doi = 10.1182/blood-2007-11-121558 }}</ref>


⚫
ViroPharma conducted a [[clinical trial#Phase III|phase III]] clinical study to evaluate the [[Prophylaxis|prophylactic]] use for the prevention of cytomegalovirus disease in recipients of [[tissue engineering|allogeneic]] [[stem cell]] transplant patients. In February 2009, ViroPharma announced that the phase III study failed to achieve its goal, showing no significant difference between maribavir and a placebo at reducing the rate at which CMV DNA levels were detected in patients.<ref>{{cite news | title=ViroPharma:Maribavir Phase III Study Missed Goal;Shares Plunge | website=CNN | date=12 February 2009 | url=http://money.cnn.com/news/newsfeeds/articles/djf500/200902091012DOWJONESDJONLINE000320_FORTUNE5.htm | archive-url=https://web.archive.org/web/20090212134018/http://money.cnn.com/news/newsfeeds/articles/djf500/200902091012DOWJONESDJONLINE000320_FORTUNE5.htm | archive-date=12 February 2009 | url-status=dead | access-date=25 November 2022}}</ref>
⚫
A Phase II study with maribavir demonstrated that [[prophylaxis]] with maribavir displayed strong antiviral activity, as measured by [[statistically significant]] reduction in the rate of reactivation of CMV in recipients of [[hematopoietic stem cell]]/[[bone marrow transplant]]s.<ref>[http://www.medicalnewstoday.com/articles/109557.php Phase 2 Data Shows Maribavir Markedly Reduced Rate Of Cytomegalovirus Infection And Disease In Bone Marrow Transplant Patients], ''Medical News Today'', 2 June 2008 {{Dead link|date=December 2021}}</ref> In an [[intent-to-treat]] analysis of the first 100 days after the transplant, the number of subjects who required pre-emptive anti-CMV therapy was statistically significantly reduced with maribavir compared to placebo.{{medcn|date=December 2021}}


⚫
The safety and efficacy of maribavir were evaluated in a phase III, multicenter, open-label, active-controlled trial that compared maribavir with a treatment assigned by a researcher running the study, which could include one or two of the following antivirals used to treat cytomegalovirus: [[ganciclovir]], [[valganciclovir]], [[foscarnet]], or [[cidofovir]].<ref name="FDA PR 20211123" /> In the study, 352 transplant recipients with cytomegalovirus infections who did not respond (with or without resistance) to treatment randomly received maribavir or treatment assigned by a researcher for up to eight weeks.<ref name="FDA PR 20211123" /> The study compared the two groups' plasma cytomegalovirus DNA concentration levels at the end of the study's eighth week, with efficacy defined as having a level below what is measurable.<ref name="FDA PR 20211123" /> Of the 235 participants who received maribavir, 56% had levels of cytomegalovirus DNA below what was measurable versus 24% of the 117 participants who received an investigator-assigned treatment.<ref name="FDA PR 20211123" />
⚫
ViroPharma conducted a [[clinical trial#Phase III|Phase III]] clinical study to evaluate the [[Prophylaxis|prophylactic]] use for the prevention of cytomegalovirus disease in recipients of [[tissue engineering|allogeneic]] [[stem cell]] transplant patients. In February 2009, ViroPharma announced that the Phase III study failed to achieve its goal, showing no significant difference between maribavir and a placebo at reducing the rate at which CMV DNA levels were detected in patients.<ref>[https://money.cnn.com/news/newsfeeds/articles/djf500/200902091012DOWJONESDJONLINE000320_FORTUNE5.htm ViroPharma:Maribavir Phase III Study Missed Goal;Shares Plunge], CNN Money, 9 February 2009 {{Dead link|date=December 2021}}</ref>


⚫
The US [[Food and Drug Administration]] (FDA) granted the application for maribavir [[orphan drug]], [[breakthrough therapy]] and [[priority review]] designations.<ref name="FDA PR 20211123" /><ref name="Takeda PR" /><ref>{{cite web | title=Maribavir Orphan Drug Designations and Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=1 February 2007 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=229906 | access-date=26 November 2021 | archive-date=27 November 2021 | archive-url=https://web.archive.org/web/20211127043920/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=229906 | url-status=live }}</ref><ref>{{cite web | title=Maribavir Orphan Drug Designations and Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=7 June 2011 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=332210 | access-date=26 November 2021 | archive-date=27 November 2021 | archive-url=https://web.archive.org/web/20211127043919/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=332210 | url-status=live }}</ref><ref name="New Drug Therapy Approvals 2021" /> The FDA granted the approval of Livtencity to Takeda Pharmaceuticals Company Limited.<ref name="FDA PR 20211123" /><ref name="Takeda PR" />
⚫
The safety and efficacy of maribavir were evaluated in a Phase III, multicenter, open-label, active-controlled trial that compared maribavir with a treatment assigned by a researcher running the study, which could include one or two of the following antivirals used to treat cytomegalovirus: [[ganciclovir]], [[valganciclovir]], [[foscarnet]], or [[cidofovir]].<ref name="FDA PR 20211123" /> In the study, 352 transplant recipients with cytomegalovirus infections who did not respond (with or without resistance) to treatment randomly received maribavir or treatment assigned by a researcher for up to eight weeks.<ref name="FDA PR 20211123" /> The study compared the two groups' plasma cytomegalovirus DNA concentration levels at the end of the study's eighth week, with efficacy defined as having a level below what is measurable.<ref name="FDA PR 20211123" /> Of the 235 participants who received maribavir, 56% had levels of cytomegalovirus DNA below what was measurable versus 24% of the 117 participants who received an investigator-assigned treatment.<ref name="FDA PR 20211123" />


== Society and culture ==
⚫
The U.S. [[Food and Drug Administration]] (FDA) granted the application for maribavir [[orphan drug]], [[breakthrough therapy]] and [[priority review]] designations.<ref name="FDA PR 20211123" /><ref name="Takeda PR" /><ref>{{cite web | title=Maribavir Orphan Drug Designations and Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=1 February 2007 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=229906 | access-date=26 November 2021}}</ref><ref>{{cite web | title=Maribavir Orphan Drug Designations and Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=7 June 2011 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=332210 | access-date=26 November 2021}}</ref> The FDA granted the approval of Livtencity to Takeda Pharmaceuticals Company Limited.<ref name="FDA PR 20211123" /><ref name="Takeda PR" />
=== Legal status ===
On 15 September 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 Livtencity, intended for the treatment of cytomegalovirus (CMV) infection and/or disease that is refractory to one or more prior therapies.<ref name="Livtencity: Pending EC decision" /> The applicant for this medicinal product is Takeda Pharmaceuticals International AG Ireland Branch.<ref name="Livtencity: Pending EC decision">{{cite web | title=Livtencity: Pending EC decision | website=[[European Medicines Agency]] (EMA) | date=14 September 2022 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/livtencity | access-date=18 September 2022 | archive-date=19 September 2022 | archive-url=https://web.archive.org/web/20220919055110/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/livtencity | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Maribavir was approved for medical use in the European Union in November 2022.<ref name="Livtencity EPAR">{{cite web | title=Livtencity EPAR | website=[[European Medicines Agency]] (EMA) | date=14 September 2022 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/livtencity | access-date=25 November 2022 | archive-date=26 November 2022 | archive-url=https://web.archive.org/web/20221126054101/https://www.ema.europa.eu/en/medicines/human/EPAR/livtencity | url-status=live }} 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=Livtencity Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1672.htm | access-date=3 March 2023 | archive-date=17 November 2022 | archive-url=https://web.archive.org/web/20221117235140/https://ec.europa.eu/health/documents/community-register/html/h1672.htm | url-status=live }}</ref>


== References ==
== References ==
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== External links ==
== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/maribavir | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Maribavir }}
* {{ClinicalTrialsGov|NCT02931539|Efficacy and Safety Study of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir}}
* {{ClinicalTrialsGov|NCT02931539|Efficacy and Safety Study of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir}}


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[[Category:Anti-herpes virus drugs]]
[[Category:Anti-herpes virus drugs]]
[[Category:Benzimidazoles]]
[[Category:Benzimidazoles]]
[[Category:Breakthrough therapy]]
[[Category:Chloroarenes]]
[[Category:Chloroarenes]]
[[Category:Isopropyl compounds]]
[[Category:Isopropylamino compounds]]
[[Category:Nucleosides]]
[[Category:Nucleosides]]
[[Category:Orphan drugs]]
[[Category:Orphan drugs]]

Latest revision as of 05:56, 10 June 2024

Maribavir
Clinical data
Trade namesLivtencity
Other names1263W94
AHFS/Drugs.comMonograph
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
  • (2S,3S,4R,5S)-2-[5,6-Dichloro-2-(propan-2-ylamino)benzimidazol-1-yl]-5-(hydroxymethyl)oxolane-3,4-diol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC15H19Cl2N3O4
Molar mass376.23 g·mol−1
3D model (JSmol)
  • CC(C)Nc1nc2cc(c(cc2n1[C@@H]3[C@H]([C@H]([C@@H](O3)CO)O)O)Cl)Cl
  • InChI=1S/C15H19Cl2N3O4/c1-6(2)18-15-19-9-3-7(16)8(17)4-10(9)20(15)14-13(23)12(22)11(5-21)24-14/h3-4,6,11-14,21-23H,5H2,1-2H3,(H,18,19)/t11-,12-,13-,14-/m0/s1 ☒N
  • Key:KJFBVJALEQWJBS-XUXIUFHCSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Maribavir, sold under the brand name Livtencity, is an antiviral medication that is used to treat post-transplant cytomegalovirus (CMV).[8][9] Maribavir is a cytomegalovirus pUL97 kinase inhibitor that works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication.[9]

The most common side effects include taste disturbance, nausea, diarrhea, vomiting and fatigue.[9]

Maribavir was approved for medical use in the United States in November 2021,[9][11] and in the European Union in November 2022.[10] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[12]

Medical uses

[edit]

In the United States, maribavir is indicated to treat people twelve years of age and older and weighing at least 35 kilograms (77 lb) with post-transplant cytomegalovirus infection/disease that does not respond (with or without genetic mutations that cause resistance) to available antiviral treatment for cytomegalovirus.[9]

In the European Union, maribavir is indicated for the treatment of cytomegalovirus (CMV) infection and/or disease that are refractory (with or without resistance) to one or more prior therapies, including ganciclovir, valganciclovir, cidofovir or foscarnet in adults who have undergone a hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT).[10]

Adverse effects

[edit]

Adverse effects of maribavir include taste disturbances, nausea, and vomiting.[13]

Contraindications

[edit]

The cytomegalovirus pUL97 kinase activates ganciclovir and valganciclovir, so coadministration with these medications is not recommended because maribavir may reduce their antiviral activity.[9]

History

[edit]

Maribavir is licensed by ViroPharma from GlaxoSmithKline in 2003, for the prevention and treatment of human cytomegalovirus (HCMV) disease in hematopoietic stem cell/bone marrow transplant patients. The mechanism by which maribavir inhibits HCMV replication is by inhibition of an HCMV encoded protein kinase enzyme called UL97 or pUL97.[14][15] Maribavir showed promise in phase II clinical trials and was granted fast track status, but failed to meet study goals in a phase III trial.[16] However, the dosage used in the phase III trial may have been too low to be efficacious.[17]

A phase II study with maribavir demonstrated that prophylaxis with maribavir displayed strong antiviral activity, as measured by statistically significant reduction in the rate of reactivation of CMV in recipients of hematopoietic stem cell/bone marrow transplants.[18] In an intent-to-treat analysis of the first 100 days after the transplant, the number of subjects who required pre-emptive anti-CMV therapy was statistically significantly reduced with maribavir compared to placebo.[19]

ViroPharma conducted a phase III clinical study to evaluate the prophylactic use for the prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplant patients. In February 2009, ViroPharma announced that the phase III study failed to achieve its goal, showing no significant difference between maribavir and a placebo at reducing the rate at which CMV DNA levels were detected in patients.[20]

The safety and efficacy of maribavir were evaluated in a phase III, multicenter, open-label, active-controlled trial that compared maribavir with a treatment assigned by a researcher running the study, which could include one or two of the following antivirals used to treat cytomegalovirus: ganciclovir, valganciclovir, foscarnet, or cidofovir.[9] In the study, 352 transplant recipients with cytomegalovirus infections who did not respond (with or without resistance) to treatment randomly received maribavir or treatment assigned by a researcher for up to eight weeks.[9] The study compared the two groups' plasma cytomegalovirus DNA concentration levels at the end of the study's eighth week, with efficacy defined as having a level below what is measurable.[9] Of the 235 participants who received maribavir, 56% had levels of cytomegalovirus DNA below what was measurable versus 24% of the 117 participants who received an investigator-assigned treatment.[9]

The US Food and Drug Administration (FDA) granted the application for maribavir orphan drug, breakthrough therapy and priority review designations.[9][11][21][22][12] The FDA granted the approval of Livtencity to Takeda Pharmaceuticals Company Limited.[9][11]

Society and culture

[edit]
[edit]

On 15 September 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 Livtencity, intended for the treatment of cytomegalovirus (CMV) infection and/or disease that is refractory to one or more prior therapies.[23] The applicant for this medicinal product is Takeda Pharmaceuticals International AG Ireland Branch.[23] Maribavir was approved for medical use in the European Union in November 2022.[10][24]

References

[edit]
  1. ^ a b "Livtencity". Therapeutic Goods Administration (TGA). 21 October 2022. Archived from the original on 5 February 2023. Retrieved 29 April 2023.
  2. ^ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 21 December 2022. Archived from the original on 3 April 2022. Retrieved 2 January 2023.
  3. ^ "LIVTENCITY (Takeda Pharmaceuticals Australia Pty Ltd)". Therapeutic Goods Administration (TGA). 11 November 2022. Archived from the original on 27 March 2023. Retrieved 29 April 2023.
  4. ^ "Therapeutic Goods (Poisons Standard—June 2024) Instrument 2024". Federal Register of Legislation. 30 May 2024. Retrieved 10 June 2024.
  5. ^ "Livtencity (Maribavir tablets) Product Monograph" (PDF). Health Canada. September 2022. Archived (PDF) from the original on 1 October 2022. Retrieved 29 April 2023.
  6. ^ "Livtencity Summary Basis of Decision". Health Canada. 23 October 2014. Archived from the original on 29 April 2023. Retrieved 10 March 2023.
  7. ^ "Details for: Livtencity". Health Canada. 25 October 2022. Archived from the original on 3 March 2024. Retrieved 3 March 2024.
  8. ^ a b "Livtencity- maribavir tablet, coated". DailyMed. Archived from the original on 19 December 2021. Retrieved 19 December 2021.
  9. ^ a b c d e f g h i j k l m "FDA Approves First Treatment for Common Type of Post-Transplant Infection that is Resistant to Other Drugs". U.S. Food and Drug Administration (FDA) (Press release). 23 November 2021. Archived from the original on 24 November 2021. Retrieved 23 November 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  10. ^ a b c d "Livtencity EPAR". European Medicines Agency (EMA). 14 September 2022. Archived from the original on 26 November 2022. Retrieved 25 November 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  11. ^ a b c "Takeda's Livtencity (maribavir) Approved by U.S. FDA as the First and Only Treatment for People Ages 12 and Older with Post-Transplant Cytomegalovirus (CMV), Refractory (With or Without Genotypic Resistance) to Conventional Antiviral Therapies". Takeda (Press release). 23 November 2021. Archived from the original on 27 November 2021. Retrieved 26 November 2021.
  12. ^ a b Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  13. ^ Winston DJ, Young JA, Pullarkat V, Papanicolaou GA, Vij R, Vance E, et al. (June 2008). "Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study". Blood. 111 (11): 5403–5410. doi:10.1182/blood-2007-11-121558. PMC 5726327. PMID 18285548.
  14. ^ Biron KK, Harvey RJ, Chamberlain SC, Good SS, Smith III AA, Davis MG, et al. (August 2002). "Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action". Antimicrobial Agents and Chemotherapy. 46 (8): 2365–2372. doi:10.1128/aac.46.8.2365-2372.2002. PMC 127361. PMID 12121906.
  15. ^ Prichard MN (July 2009). "Function of human cytomegalovirus UL97 kinase in viral infection and its inhibition by maribavir". Reviews in Medical Virology. 19 (4): 215–229. doi:10.1002/rmv.615. PMC 3777615. PMID 19434630.
  16. ^ Marty FM, Ljungman P, Papanicolaou GA, Winston DJ, Chemaly RF, Strasfeld L, et al. (April 2011). "Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial". The Lancet. Infectious Diseases. 11 (4): 284–292. doi:10.1016/S1473-3099(11)70024-X. PMID 21414843.
  17. ^ Snydman DR (April 2011). "Why did maribavir fail in stem-cell transplants?". The Lancet. Infectious Diseases. 11 (4): 255–257. doi:10.1016/S1473-3099(11)70033-0. PMID 21414844.
  18. ^ "Phase 2 Data Shows Maribavir Markedly Reduced Rate Of Cytomegalovirus Infection And Disease In Bone Marrow Transplant Patients" (Press release). ViroPharma. 30 August 2008. Archived from the original on 3 January 2009. Retrieved 25 November 2022 – via Medical News Today.
  19. ^ Winston DJ, Young JA, Pullarkat V, Papanicolaou GA, Vij R, Vance E, et al. (June 2008). "Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study". Blood. 111 (11): 5403–5410. doi:10.1182/blood-2007-11-121558. PMC 5726327. PMID 18285548.
  20. ^ "ViroPharma:Maribavir Phase III Study Missed Goal;Shares Plunge". CNN. 12 February 2009. Archived from the original on 12 February 2009. Retrieved 25 November 2022.
  21. ^ "Maribavir Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 1 February 2007. Archived from the original on 27 November 2021. Retrieved 26 November 2021.
  22. ^ "Maribavir Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 7 June 2011. Archived from the original on 27 November 2021. Retrieved 26 November 2021.
  23. ^ a b "Livtencity: Pending EC decision". European Medicines Agency (EMA). 14 September 2022. Archived from the original on 19 September 2022. Retrieved 18 September 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  24. ^ "Livtencity Product information". Union Register of medicinal products. Archived from the original on 17 November 2022. Retrieved 3 March 2023.
[edit]
  • Clinical trial number NCT02931539 for "Efficacy and Safety Study of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir" at ClinicalTrials.gov
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Maribavir&oldid=1228243849"