EU Approves Livtencity (Maribavir) for Refractory Cytomegalovirus Infections in Transplant Recipients
Takeda
Biopharmaceutical Manufacturer
European Commission
The European Commission, abbreviated as the EU Commission, is a supranational body under the European Union. Within the EU political system, the European Commission primarily undertakes executive tasks, thus being roughly equivalent to the government in a national system. However, the European Commission has other functions as well. In particular, except for the few circumstances specified in the treaties, the European Commission is the only institution with legislative power in the EU legislative process.
Image Source: Shutterstock
News on November 10, 2022 /BioValleyBIOON/ -- Takeda Pharmaceutical Company Limited recently announced that the European Commission (EC) has approvedOral antiviral drug Livtencity (maribavir): Used for patients who have undergone hematopoieticStem CellsAdult patients undergoing hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), treating post-transplant cytomegalovirus (CMV) infection and/or disease that is refractory to (with or without resistance) one or more prior therapies, including ganciclovir, valganciclovir, cidofovir, and foscarnet.。CMV is one of the most common and serious post-transplant infections, which can lead to loss of the transplanted organ and transplant failure.
It is worth mentioning that,Livtencity is the first and only therapy approved by the European Union (EU) for the aforementioned indication.. At the same time,Livtencity is the first and only oral antiviral therapy that targets and inhibits the CMV-specific pUL97 protein kinase and its natural substrates.Livtencity blocks viral replication by inhibiting the activity of the CMV protein kinase pUL97.
November 2021,Livtencity has been approved in the United StatesFDAApproved as the first drug in the United States for treating post-transplant CMV infections that are refractory to conventional antiviral therapies (with or without genotypic resistance).Livtencity is indicated for: adult and pediatric patients (aged ≥12 years, weighing ≥35 kg) who have received SOT or HSCT, for the treatment of post-transplant CMV infection that is refractory to (with or without genotypic resistance) ganciclovir, valganciclovir, foscarnet, or cidofovir.
In patients undergoing SOT and HSCT, CMV infection is a common and serious clinical complication that can lead to severe consequences, including graft failure and even death. Data from the pivotal Phase 3 SOLSTICE (TAK-620-303, NCT02931539) trial show:In transplant recipients with refractory, with or without resistance (R/R) CMV infection/disease, maribavir is superior to IAT in clearing CMV viremia, clearing viremia while maintaining symptom control, with lower treatment-related toxicity and fewer patients discontinuing treatment due to treatment-emergent adverse events (TEAE).
Maribavir Molecular Structure (Image Source: wikimedia.org)
CMV is a β-herpesvirus that commonly infects humans; there is serological evidence of prior infection in 40%-100% of the adult population.CMV is usually latent and asymptomatic in the body, butImmunityReactivation may occur during the suppression period. Severe disease may develop in individuals with compromised immune systems, including patients receiving immunosuppressive therapy related to various types of transplants, such as hematopoietic cell transplantation (HCT) or solid organ transplantation (SOT). Among the estimated 200,000 adult transplant cases each year,CMV is one of the most common viral infections in transplant recipients, with an estimated incidence of 16-56% in SOT recipients and 30-80% in HCT recipients.。
In transplant recipients, reactivation of CMV can lead to serious consequences, including loss of the transplanted organ and, in extreme cases, can be fatal.Existing therapies for treating CMV infection post-transplant may exhibit severe side effects, require dose adjustments, or fail to adequately suppress viral replication. Additionally, existing therapies may necessitate or prolong hospitalization due to the administration of treatment.
The active pharmaceutical ingredient maribavir in Livtencity is an orally bioavailable anti-cytomegalovirus (CMV) compound and the first CMV antiviral drug that targets and inhibits the pUL97 protein kinase and its natural substrates. Current CMVManagementRelated to difficult trade-offs, including the management of toxicity and clearance of viremia.Livtencity has the potential to redefine the treatment of refractory CMV post-transplant, with or without resistance.
Maribavir belongs to a class of drugs called benzimidazole nucleosides, which can target and inhibit the pUL97 protein kinase of CMV, potentially affecting several key processes of CMV replication, including viral DNA replication, viral gene expression, capsid formation, and the escape of mature capsids from the nucleus of infected cells.
Results of the SOLSTICE Trial (Image source: PMC9464078)
SOLSTICE (TAK-620-303) is an open-label Phase 3 study conducted in transplant recipients with refractory, with or without resistance (R/R), cytomegalovirus (CMV) infection/disease. The study compared maribavir with conventional antiviral drugs (Investigator-Assigned Treatment [IAT], a combination of one or more of the following drugs: ganciclovir, valganciclovir, foscarnet, cidofovir). The primary endpoint of the study was the confirmed CMV viremia clearance rate at the end of Week 8 of treatment, and the key secondary endpoint was achieving CMV clearance by Week 8 and maintaining symptom control until Week 16.
The results showed,The study met the primary endpoint and key secondary endpoints: (1) At the end of Week 8 of treatment, the proportion of patients achieving confirmed clearance of CMV viremia in the maribavir group was more than double that of the IAT group (55.7% vs 23.9%; adjusted difference [95% CI]: 32.8% [22.80-42.74]; p<0.001); (2) The proportion of patients who achieved CMV clearance and maintained symptom control from Week 8 to Week 16 was more than double in the maribavir group compared to the IAT group (18.7% vs 10.3%; adjusted difference [95% CI]: 9.5% [2.02-16.88]; p=0.01).
The data from the subgroup analysis showed that: Among transplant recipients confirmed to have genotypic resistant CMV infection at baseline, the proportion of patients achieving confirmed CMV viremia clearance at Week 8 of the study (end of the treatment period) was more than three times higher in the maribavir group compared to the IAT group (62.8% vs 20.3%; adjusted difference [95% CI]: 44.1% [31.3, 56.9]).
In the study, the incidence of treatment-emergent adverse events (TEAEs) was similar between the two groups (maribavir group 97.4%; IAT group 91.4%). Compared with foscarnet, maribavir had a lower incidence of acute kidney injury (8.5% vs 21.3%), and compared with valganciclovir/ganciclovir, it had a lower incidence of neutropenia (9.4% vs 33.9%). Fewer patients in the maribavir group discontinued treatment due to TEAEs (13.2%) compared with the IAT group (31.9%). One patient in each group experienced fatal treatment-related TEAEs. (Bioon.com)