Maribavir, sold under the brand name Livtencity, is an

antiviral medication Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobial ...

that is used to treat post-transplant

cytomegalovirus ''Cytomegalovirus'' (CMV) (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order '' Herpesvirales'', in the family '' Herpesviridae'', in the subfamily '' Betaherp ...

(CMV). Maribavir is a cytomegalovirus pUL97 kinase inhibitor that works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication. The most common side effects include taste disturbance, nausea, diarrhea, vomiting and fatigue. Maribavir was approved for medical use in the United States in November 2021, and in the European Union in November 2022. The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medic ...

Medical uses

In the United States, maribavir is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

to treat people twelve years of age and older and weighing at least with post-transplant cytomegalovirus infection/disease that does not respond (with or without genetic mutations that cause resistance) to available antiviral treatment for cytomegalovirus. 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 Ganciclovir, sold under the brand name Cytovene among others, is an antiviral medication used to treat cytomegalovirus (CMV) infections. Ganciclovir was patented in 1980 and approved for medical use in 1988. Medical use Ganciclovir is indicated ...

, valganciclovir,

cidofovir Cidofovir, brand name Vistide, is a topical or injectable antiviral medication primarily used as a treatment for cytomegalovirus (CMV) retinitis (an infection of the retina of the eye) in people with AIDS. Cidofovir was approved for medical ...

foscarnet 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 Structural analog, analog ...

in adults who have undergone a hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT).

Adverse effects

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

Contraindications

The cytomegalovirus pUL97 kinase activates

and valganciclovir, so coadministration with these medications is not recommended because maribavir may reduce their antiviral activity.

History

Maribavir is licensed by

ViroPharma 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 h ...

from

GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

in 2003, for the

prevention Prevention may refer to: Health and medicine * Preventive healthcare, measures to prevent diseases or injuries rather than curing them or treating their symptoms General safety * Crime prevention, the attempt to reduce deter crime and crimin ...

and treatment of human

(HCMV) disease in

hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the ...

bone marrow transplant Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce a ...

patients. The mechanism by which maribavir inhibits HCMV replication is by inhibition of an HCMV encoded

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them ( phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a f ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

called UL97 or pUL97. 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. However, the dosage used in the phase III trial may have been too low to be efficacious. A phase II study with maribavir demonstrated that

prophylaxis Preventive healthcare, or prophylaxis, is the application of healthcare measures to prevent diseases.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental health a ...

with maribavir displayed strong antiviral activity, as measured by

statistically significant In statistical hypothesis testing, a result has statistical significance when a result at least as "extreme" would be very infrequent if the null hypothesis were true. More precisely, a study's defined significance level, denoted by \alpha, is the ...

reduction in the rate of reactivation of CMV in recipients of

s. 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. ViroPharma conducted a phase III clinical study to evaluate the

prophylactic Preventive healthcare, or prophylaxis, is the application of healthcare measures to prevent diseases.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental health a ...

use for the prevention of cytomegalovirus disease in recipients of

allogeneic Allotransplant (''allo-'' meaning "other" in Greek) is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, ...

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of 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. 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:

, valganciclovir,

, or

. 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. 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. 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. The US

(FDA) granted the application for maribavir

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "b ...

and

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

designations. The FDA granted the approval of Livtencity to Takeda Pharmaceuticals Company Limited.

Society and culture

Legal status

On 15 September 2022, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

(CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(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. The applicant for this medicinal product is Takeda Pharmaceuticals International AG Ireland Branch. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Maribavir was approved for medical use in the European Union in November 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

References

External links

* {{Portal bar , Medicine , Viruses Anti-herpes virus drugs Benzimidazoles Chloroarenes Isopropylamino compounds Nucleosides Orphan drugs