Takeda Presents New Exploratory Analysis Showing Patients Treated With LIVTENCITY™ (Maribavir) Had Reductions in Hospitalization Rates and Length of Hospital Stay
- Data Include Exploratory Analysis Showing LIVTENCITY Treated Patients With Post-Transplant Cytomegalovirus (CMV) Infections/Disease Had Reductions in Hospitalizations (34.8%; p=0.021) and Length of Hospital Stay (53.8%; p=0.029) Compared to Those Treated With Conventional Antiviral Therapies 1*
- Post-Hoc Analyses by Subgroup Showed Shorter Time to First Confirmed CMV DNA Level Less Than the Lower Limit of Quantification (<LLOQ) With LIVTENCITY Compared to Conventional Antiviral Therapies, Consistent With Previously Reported Findings 2
Data Presented at the 2022
Tandem Meetings and European Congressof Clinical Microbiology and Infectious Diseases (ECCMID) Builds Upon the Growing Body of Evidence Supporting LIVTENCITY’s Role in Redefining Treatment for Patients With Post-Transplant CMV Infections 1–4
The abstracts include additional analyses that underscore the relevance of the multicenter, randomized, open-label Phase 3 SOLSTICE trial data, which supported the
CMV is one of the most common and serious post-transplant infections with an estimated global incidence rate of around 16-56% in solid organ transplant (SOT) recipients and 30-70% in HSCT recipients,7–12 and can lead to serious consequences, including loss of the transplanted organ and failure of the graft.13,14
“When managing post-transplant CMV infections, we're always looking for additional treatment options for patients that are refractory with or without resistance,” said
Highlights of data being presented at the 2022 Tandem Meetings include:
Healthcare Resource Utilization in Transplant Recipients With Cytomegalovirus Infection Refractory/Resistant to Treatment Receiving LIVTENCITY Versus Investigator Assigned Therapy: Exploratory Analysis of a Phase 3 Trial
- Data from an exploratory analysis of the Phase 3 SOLSTICE trial evaluating the impact of treatment with LIVTENCITY compared to conventional antiviral therapies on healthcare utilization, including number of patients with ≥1 hospitalization and length of hospital stay will be presented [Poster #52].1
- This analysis aimed to quantify the healthcare resource utilization experience of patients requiring treatment for post-transplant CMV. During the treatment phase, 31.9% of patients treated with LIVTENCITY (n=75/235) had at least one hospitalization compared to 36.8% of patients treated with conventional therapies (n=43/117). Adjusting for time on treatment, the LIVTENCITY treatment group had a 34.8% reduction compared to the conventional therapy group (p=0.021). The length of hospital stay during the treatment phase (adjusting for time on treatment) was 13.27 days/person/year in LIVTENCITY-treated patients compared to 28.73 for those conventionally treated, a 53.8% decrease (p=0.029). Reducing hospitalizations is a critical part of reducing disease burden to healthcare systems.1
Population Pharmacokinetics and Exposure-Response Relationships of LIVTENCITY in Transplant Recipients With Cytomegalovirus Infections
- Data from population pharmacokinetic and pharmacodynamic (PK/PD) models based on Phase 1, 2 and 3 (SOLSTICE) studies, which were developed to characterize LIVTENCITY plasma concentrations and exposure-response relationships, which support dosage recommendations, will be presented [Poster #470].4
- PK/PD modeling results suggest that dose adjustments of LIVTENCITY will not be required in adult transplant patients for the treatment of CMV infection regardless of age, body weight, sex, race, transplant type, baseline plasma CMV DNA, or presence of CMV mutations.4
Assessment of Discontinuations and Anti-Cytomegalovirus Treatment Switching in Post-Transplant Refractory/Resistant Cytomegalovirus Infections: Safety and Sensitivity Analyses From a Phase 3 Randomized Trial
- Data from a safety and sensitivity analysis of the Phase 3 SOLSTICE trial, assessing the impact of discontinuations or treatment switching on achieving confirmed CMV DNA level <LLOQ (lower limit of quantification, i.e. <137 IU/mL), will be presented [Poster #467].3
Highlights of data being presented at ECCMID include:
Kaplan-Meier Estimates of Time to First Cytomegalovirus Viremia Clearance in Transplant Recipients With Refractory Cytomegalovirus Infection With or Without Resistance Receiving LIVTENCITY Versus Investigator-Assigned Therapy: Subgroup Analyses of a Phase 3 Trial
- Data from a subgroup analysis of the Phase 3 SOLSTICE trial assessing median time to first confirmed CMV DNA level <LLOQ will be presented [Abstract #O0059].2
- Post-hoc analyses by subgroups, including baseline resistance status and transplant type, were consistent with previously reported results, demonstrating a shorter time to confirmed CMV DNA level <LLOQ for LIVTENCITY compared to conventional antiviral therapies. In patients with low baseline viral load, median time to first CMV DNA level <LLOQ was 15 days (95% CI: 13-17) for LIVTENCITY and 22 days (95% CI: 20-29) for conventional antiviral therapies, and 43 (95% CI: 30-49) and 44 days (95% CI: 26-NA) respectively for patients with intermediate/high viral load.2
CMV is a beta herpesvirus that commonly infects humans; serologic evidence of prior infection can be found in 40%-100% of various adult populations.15,16 CMV typically resides latent and asymptomatic in the body but may reactivate during periods of immunosuppression. Serious disease may occur in individuals with compromised immune systems, which includes patients
In transplant recipients, reactivation of CMV can lead to serious consequences including loss of the transplanted organ and, in extreme cases, can be fatal.13,14 Existing therapies to treat post-transplant CMV infections may demonstrate serious side effects that require dose adjustments or may fail to adequately suppress viral replication.17,18 Additionally, existing therapies may require or prolong hospitalization due to administration.17,18
About LIVTENCITYTM (Maribavir)
LIVTENCITY (maribavir), an orally bioavailable anti-CMV compound, is the first and only antiviral agent that targets and inhibits the pUL97 protein kinase.5 It is approved in the
About Takeda’s SOLSTICE Trial
The TAK-620-303 (SOLSTICE) trial (NCT02931539) was a multicenter, randomized, open-label, active-controlled superiority trial to assess the efficacy and safety comparing treatment with either LIVTENCITY (maribavir) or conventional antiviral therapy in 352 hematopoietic cell transplant and solid organ transplant recipients with CMV infection refractory, with or without resistance, to one or a combination of the conventional antiviral therapies: ganciclovir, valganciclovir, foscarnet or cidofovir. Adult patients underwent a 2-week screening period, followed by randomization 2:1 to LIVTENCITY (n=235) (400 mg, twice daily) or conventional antiviral therapies (n=117) (as dosed by the investigator) for up to 8-weeks. After completion of the treatment period, subjects entered a 12-week follow-up phase.6
The trial’s primary endpoint was confirmed CMV DNA level <LLOQ (lower limit of quantification, [i.e. <137 IU/mL] in 2 consecutive samples separated by at least 5 days as assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test at the end of Week 8). The key secondary endpoint was CMV DNA level <LLOQ and CMV infection symptom control§ at the end of Study Week 8 with maintenance of this treatment effect through Study Week 16.6
LIVTENCITY is indicated for the treatment of adults and pediatric patients (12 years of age and older and weighing at least 35 kg) with post-transplant cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir or foscarnet.5
IMPORTANT SAFETY INFORMATION
Risk of Reduced Antiviral Activity When Co-administered with Ganciclovir and Valganciclovir
LIVTENCITY may antagonize the antiviral activity of ganciclovir and valganciclovir by inhibiting human CMV pUL97 kinase, which is required for activation/phosphorylation of ganciclovir and valganciclovir. Coadministration of LIVTENCITY with ganciclovir or valganciclovir is not recommended.
Virologic Failure During Treatment and Relapse Post-Treatment
Virologic failure due to resistance can occur during and after treatment with LIVTENCITY. Virologic relapse during the posttreatment period usually occurred within 4-8 weeks after treatment discontinuation. Some maribavir pUL97 resistance-associated substitutions confer cross-resistance to ganciclovir and valganciclovir. Monitor CMV DNA levels and check for maribavir resistance if the patient is not responding to treatment or relapses.
Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions
The concomitant use of LIVTENCITY and certain drugs may result in potentially significant drug interactions, some of which may lead to reduced therapeutic effect of LIVTENCITY or adverse reactions of concomitant drugs. Consider the potential for drug interactions prior to and during LIVTENCITY therapy; review concomitant medications during LIVTENCITY therapy and monitor for adverse reactions.
Refer to the full prescribing information of LIVTENCITY for important drug interactions.
Maribavir is primarily metabolized by CYP3A4. Drugs that are strong inducers of CYP3A4 are expected to decrease maribavir plasma concentrations and may result in reduced virologic response; therefore, coadministration of LIVTENCITY with these drugs is not recommended, except for selected anticonvulsants.
Use With Immunosuppressant Drugs
LIVTENCITY has the potential to increase the drug concentrations of immunosuppressant drugs that are CYP3A and/or P-gp substrates where minimal concentration changes may lead to serious adverse events (including tacrolimus, cyclosporine, sirolimus and everolimus). Frequently monitor immunosuppressant drug levels throughout treatment with LIVTENCITY, especially following initiation and after discontinuation of LIVTENCITY and adjust immunosuppressant dose, as needed.
The most common adverse events (all grades,> 10%) in subjects treated with LIVTENCITY were taste disturbance, nausea, diarrhea, vomiting, and fatigue.
Please click for Full Prescribing Information .
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* Conventional antiviral therapies: ganciclovir, valganciclovir, cidofovir, or foscarnet
§CMV infection symptom control was defined as resolution or improvement of tissue-invasive disease or CMV syndrome for symptomatic patients at baseline, or no new symptoms for patients
† Refractory defined as documented failure to achieve >1 log10 decrease in CMV DNA level in whole blood or plasma after a 14 day or longer treatment period with IV ganciclovir/oral valganciclovir, IV foscarnet, or IV cidofovir
‡ Resistant defined as refractory CMV and documentation of >1 CMV genetic mutations associated with resistance to ganciclovir, valganciclovir, foscarnet, and/or cidofovir
- Hirji I, et al. Healthcare resource utilization in transplant recipients with cytomegalovirus infection refractory/resistant to treatment receiving LIVTENCITY versus investigator assigned therapy: Exploratory analysis of a Phase 3 trial. In: The 2022 Tandem Transplantation & Cellular Therapy (TCT) Meetings Of ASTCT and CIBMTR. 2022. Abstract 52.
Alain S, et al. Time to First Cytomegalovirus Viremia Clearance in Transplant Recipients with Refractory Cytomegalovirus Infection With or Without Resistance Receiving Maribavir Versus Investigator-Assigned Therapy: Subgroup Analyses of a Phase 3 Trial. In: The 32nd
European Congress of Clinical Microbiology and Infectious Diseases. 2022. Abstract O0059.
- Alexander B, et al. Assessment of Discontinuations and Anti-Cytomegalovirus Treatment Switching in Post-Transplant Refractory/Resistant Cytomegalovirus Infections: Safety and Sensitivity Analyses from a Phase 3 Randomized Trial. In: The 2022 Tandem Transplantation & Cellular Therapy (TCT) Meetings Of ASTCT and CIBMTR. 2022. Abstract 467.
- Song I, et al. Population Pharmacokinetics and Exposure–Response Relationships of LIVTENCITY in Transplant Recipients with Cytomegalovirus Infections. In: The 2022 Tandem Transplantation & Cellular Therapy (TCT) Meetings Of ASTCT and CIBMTR. 2022. Abstract 470.
USPI. Takeda Internal Communication (TAK620-INT) Manufacturing Information.
November 2021. 2021 Takeda Pharmaceuticals USA Inc.All rights reserved.
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- Stern L, et al. Human Cytomegalovirus Latency and Reactivation in Allogeneic Hematopoietic Stem Cell Transplant Recipients. Front Microbiol. 2019;10:1186.
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- Chemaly RF, et al. Definitions of Resistant and Refractory Cytomegalovirus Infection and Disease in Transplant Recipients for Use in Clinical Trials. Clin Infect Dis. 2019;68(8):1420-1426.