Maribavir

Last updated

Maribavir
Maribavir.svg
Clinical data
Trade names Livtencity
Other names1263W94
AHFS/Drugs.com Monograph
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
Formula C15H19Cl2N3O4
Molar mass 376.23 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 X mark.svgN
  • Key:KJFBVJALEQWJBS-XUXIUFHCSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Maribavir, sold under the brand name Livtencity, is an antiviral medication that is used to treat post-transplant cytomegalovirus (CMV). [6] [7] Maribavir is a cytomegalovirus pUL97 kinase inhibitor that works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication. [7]

Contents

The most common side effects include taste disturbance, nausea, diarrhea, vomiting and fatigue. [7]

Maribavir was approved for medical use in the United States in November 2021, [7] [9] and in the European Union in November 2022. [8] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. [10]

Medical uses

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. [7]

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). [8]

Adverse effects

Adverse effects of maribavir include taste disturbances, nausea, and vomiting. [11]

Contraindications

The cytomegalovirus pUL97 kinase activates ganciclovir and valganciclovir, so coadministration with these medications is not recommended because maribavir may reduce their antiviral activity. [7]

History

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. [12] [13] 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. [14] However, the dosage used in the phase III trial may have been too low to be efficacious. [15]

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. [16] 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. [17]

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. [18]

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. [7] 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. [7] 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. [7] 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. [7]

The US Food and Drug Administration (FDA) granted the application for maribavir orphan drug, breakthrough therapy and priority review designations. [7] [9] [19] [20] [10] The FDA granted the approval of Livtencity to Takeda Pharmaceuticals Company Limited. [7] [9]

Society and culture

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. [21] The applicant for this medicinal product is Takeda Pharmaceuticals International AG Ireland Branch. [21] Maribavir was approved for medical use in the European Union in November 2022. [8] [22]

Related Research Articles

<span class="mw-page-title-main">Graft-versus-host disease</span> Medical condition

Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.

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

Ganciclovir, sold under the brand name Cytovene among others, is an antiviral medication used to treat cytomegalovirus (CMV) infections.

<span class="mw-page-title-main">Valganciclovir</span> Antiviral medication

Valganciclovir, sold under the brand name Valcyte among others, is an antiviral medication used to treat cytomegalovirus (CMV) infection in those with HIV/AIDS or following organ transplant. It is often used long term as it only suppresses rather than cures the infection. Valganciclovir is taken by mouth.

<span class="mw-page-title-main">Cytomegalovirus retinitis</span> Medical condition

Cytomegalovirus retinitis, also known as CMV retinitis, is an inflammation of the retina of the eye that can lead to blindness. Caused by human cytomegalovirus, it occurs predominantly in people whose immune system has been compromised, 15-40% of those with AIDS.

<span class="mw-page-title-main">Alemtuzumab</span> Medication used to treat chronic lymphocytic leukemia (CLL)

Alemtuzumab, sold under the brand names Campath and Lemtrada among others, is a medication used to treat chronic lymphocytic leukemia (CLL) and multiple sclerosis. In CLL, it has been used as both a first line and second line treatment. In MS it is generally only recommended if other treatments have not worked. It is given by injection into a vein.

<span class="mw-page-title-main">ViroPharma</span>

ViroPharma Incorporated was a pharmaceutical company that developed and sold drugs that addressed serious diseases treated by physician specialists and in hospital settings. The company focused on product development activities on viruses and human disease, including those caused by cytomegalovirus (CMV) and hepatitis C virus (HCV) infections. It was purchased by Shire in 2013, with Shire paying around $4.2 billion for the company in a deal that was finalized in January 2014. ViroPharma was a member of the NASDAQ Biotechnology Index and the S&P 600.

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

Foscarnet (phosphonomethanoic acid), known by its brand name Foscavir, is an antiviral medication which is primarily used to treat viral infections involving the Herpesviridae family. It is classified as a pyrophosphate analog DNA polymerase inhibitor. Foscarnet is the conjugate base of a chemical compound with the formula HO2CPO3H2 (Trisodium phosphonoformate).

<i>Human betaherpesvirus 5</i> Species of virus

Human betaherpesvirus 5, also called human cytomegalovirus (HCMV), is species of virus in the genus Cytomegalovirus, which in turn is a member of the viral family known as Herpesviridae or herpesviruses. It is also commonly called CMV. Within Herpesviridae, HCMV belongs to the Betaherpesvirinae subfamily, which also includes cytomegaloviruses from other mammals. CMV is a double-stranded DNA virus.

<span class="mw-page-title-main">Maraviroc</span> Antiretroviral drug

Maraviroc, sold under the brand names Selzentry (US) and Celsentri (EU), is an antiretroviral medication used to treat HIV infection. It is taken by mouth. It is in the CCR5 receptor antagonist class.

<span class="mw-page-title-main">Pleconaril</span> Antiviral drug

Pleconaril (Picovir) is an antiviral drug that was being developed by Schering-Plough for prevention of asthma exacerbations and common cold symptoms in patients exposed to picornavirus respiratory infections. Pleconaril, administered either orally or intranasally, is active against viruses in the Picornaviridae family, including Enterovirus and Rhinovirus. It has shown useful activity against the dangerous enterovirus D68.

A Cytomegalovirus vaccine is a vaccine to prevent cytomegalovirus (CMV) infection or curb virus re-activation in persons already infected. Challenges in developing a vaccine include adeptness of CMV in evading the immune system and limited animal models. As of 2018 no such vaccine exists, although a number of vaccine candidates are under investigation. They include recombinant protein, live attenuated, DNA and other vaccines.

<span class="mw-page-title-main">Blueberry muffin baby</span> Medical condition

Blueberry muffin baby, also known as extramedullary hematopoiesis, describes a newborn baby with multiple purpura, associated with several non-cancerous and cancerous conditions in which extra blood is produced in the skin. The bumps range from one to seven mm, do not blanch and have a tendency to occur on the head, neck and trunk. They often fade by three to six weeks after birth, leaving brownish marks. When due to a cancer, the bumps tend to be fewer, firmer and larger.

Cytomegalovirus esophagitis is a form of esophagitis associated with cytomegalovirus. Symptoms include dysphagia, upper abdominal pain, diarrhea, nausea, vomiting, and sometimes hematemesis. This condition occurs in the setting of patients with a weakened immune system who are susceptible to both infections by CMV and the manifestation of symptoms. A large majority of patient that have CMV Esophagitis are diagnosed with HIV. Another significant segment of the population have weakened immune systems through transplant surgery, diabetes, or due to medication. Diagnosis is done primarily by endoscopy with biopsy, as CMV Esophagitis has a distinctive pathology pattern of linear ulcers.

<span class="mw-page-title-main">Congenital cytomegalovirus infection</span> Medical condition

Congenital cytomegalovirus (cCMV) is cytomegalovirus (CMV) infection in a newborn baby. Most have no symptoms. Some affected babies are small. Other signs and symptoms include a rash, jaundice, hepatomegaly, retinitis, and seizures. It may lead to loss of hearing or vision, developmental disability, or a small head.

<span class="mw-page-title-main">Cytomegalovirus colitis</span> Medical condition

Cytomegalovirus colitis, also known as CMV colitis, is an inflammation of the colon.

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

Pritelivir is a direct-acting antiviral drug in development for the treatment of herpes simplex virus infections (HSV). This is particularly important in immune compromised patients. Pritelivir is currently in Phase III clinical development by the German biopharmaceutical company AiCuris Anti-infective Cures AG.

<span class="mw-page-title-main">Letermovir</span> Antiviral drug

Letermovir is an antiviral drug for the treatment of cytomegalovirus (CMV) infections. It has been tested in CMV infected patients with allogeneic stem cell transplants and may also be useful for other patients with a compromised immune system such as those with organ transplants or HIV infections. The drug was initially developed by the anti-infective division at Bayer, which became AiCuris Anti-infective Cures AG through a spin-out and progressed the development to end of Phase 2 before the project was sold to Merck & Co for Phase 3 development and approval.

<span class="mw-page-title-main">Brincidofovir</span> Antiviral drug

Brincidofovir, sold under the brand name Tembexa, is an antiviral drug used to treat smallpox. Brincidofovir is a prodrug of cidofovir. Conjugated to a lipid, the compound is designed to release cidofovir intracellularly, allowing for higher intracellular and lower plasma concentrations of cidofovir, effectively increasing its activity against dsDNA viruses, as well as oral bioavailability.

Cecilia Söderberg-Nauclér, born 1967, is a Swedish immunologist who is Professor of Microbial Pathogenesis at the Karolinska Institute. In 2013, she demonstrated that a simple antiviral could improve the life expectancy of glioblastoma disease. During the COVID-19 pandemic in Sweden, Söderberg-Nauclér on several occasions strongly criticized the Swedish response to SARS-CoV-2, claiming that they were leading the country into a catastrophe, and demanded that the Swedish state epidemiologist should resign.

<span class="mw-page-title-main">Molnupiravir</span> Antiviral medication

Molnupiravir, sold under the brand name Lagevrio, is an antiviral medication that inhibits the replication of certain RNA viruses. It is used to treat COVID-19 in those infected by SARS-CoV-2. It is taken by mouth.

References

  1. 1 2 "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. ↑ "Livtencity (Maribavir tablets) Product Monograph" (PDF). Takeda Canada Inc. September 2022. Archived (PDF) from the original on 1 October 2022. Retrieved 29 April 2023.
  5. ↑ "Livtencity Summary Basis of Decision". Health Canada. 23 October 2014. Archived from the original on 29 April 2023. Retrieved 10 March 2023.
  6. 1 2 "Livtencity- maribavir tablet, coated". DailyMed. Archived from the original on 19 December 2021. Retrieved 19 December 2021.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 "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.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  8. 1 2 3 4 "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.
  9. 1 2 3 "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.
  10. 1 2 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.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ "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.
  17. ↑ 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.
  18. ↑ "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.
  19. ↑ "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.
  20. ↑ "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.
  21. 1 2 "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.
  22. ↑ "Livtencity Product information". Union Register of medicinal products. Archived from the original on 17 November 2022. Retrieved 3 March 2023.
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.