LIVTENCITY® (maribavir) for Healthcare Professionals

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at post-transplant refractory CMV

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.

Efficacy and safety were evaluated in a Phase 3, multicenter, randomized, open-label, active-controlled superiority trial of 352 adult SOT or HCT transplant recipients with refractory or resistant CMV. Patients were randomized and treated with LIVTENCITY (N=235, 400 mg twice daily) or IAT* (N=117, as dosed by the investigator) for 8 weeks, with a 12-week follow-up. Primary endpoint was defined as confirmed CMV DNA level <LLOQ (ie, <137 IU/mL in 2 consecutive samples tested ≥5 days apart) at the end of Week 8.^1,2

PRIMARY ENDPOINT:

STATISTICAL SUPERIORITY ACHIEVED AT WEEK 8 vs IAT

LIVTENCITY was statistically superior to IAT in achievement of CMV DNA level <LLOQ (<137 IU/mL^†) at Week 8 (56% [131/235] vs 24% [28/117]; 33% adjusted difference; 95% CI [23, 43]; P<0.001)^1‡

EXPLORE EFFICACY RESULTS

ESTABLISHED SAFETY DATA

Phase 3 clinical trial evaluated safety in 352 adult SOT or HCT transplant recipients with refractory or resistant CMV¹

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OFFERS CONVENIENCE OF AN ORAL FORMULATION

Recommended dose: 400 mg (two 200 mg tablets) twice daily for both adults and children 12 years of age and older weighing at least 77 pounds (35 kg)¹

Patients receiving concomitant treatment with certain drugs, including immunosuppressants, should be closely monitored¹
Dose adjustments are needed when LIVTENCITY is co-administered with certain anticonvulsants¹

DISCOVER DOSING

Post-transplant patients experience challenges with refractory or resistant CMV.

EXAMINE CURRENT CHALLENGES

CMV=cytomegalovirus; HCT=hematopoietic cell transplant; IAT=investigator-assigned treatment; SOT=solid organ transplant.

^*Investigator-assigned anti-CMV treatment with 1 or 2 of the conventional CMV antivirals: Ganciclovir, valganciclovir, foscarnet, and/or cidofovir. Combination therapy with cidofovir and foscarnet was not permitted. Changes to dose or dosing schedule were permitted. Discontinuation of one of the combination agents was permitted. Only switches between ganciclovir and valganciclovir were permitted.^1,2
^†As assessed by COBAS^® AmpliPrep/COBAS^® TaqMan^® CMV test.¹
^‡Cochran-Mantel-Haenszel weighted average approach was used for the adjusted difference in proportion of responders (MBV-IAT), 95% CI, and p-value, after adjusting for transplant type and baseline plasma CMV DNA level concentration. Computation included only those with both stratification factors.¹

1. Livtencity (maribavir) Prescribing Information. Lexington, MA: Takeda Pharmaceuticals U.S.A., Inc. 2. Data on file. Takeda Pharmaceuticals U.S.A., Inc. 3. Avery RK, Alain S, Alexander BD, et al. Clin Infect Dis. 2022;75(4):690-701. 4. Avery RK, Alain S, Alexander BD, et al. Clin Infect Dis. Supplement. 2022. doi.org/10.1093/cid/ciab988. 5. Shannon-Lowe CD, Emery VC. Herpesviridae. 2010;1(4):1-13. 6. Steingruber M, Marschall M. Microorganisms. 2020;8(4):515. 7. Biron KK, Harvey RJ, Chamberlain SC, et al. Antimicrob Agents Chemother 2002;46:2365-2372. 8. Wolf DG, Courcelle CT, Prichard MN, Mocarski ES. Proc Natl Acad Sci U S A. 2001;98(4):1895-1900. 9. Krosky PM, Baek MC, Coen DM. J Virol. 2003;77:905-914. 10. Bigley TM, Reitsma JM, Mirza SP, Terhune SS. J Virol. 2013;87(13):7393-7408.

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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.

Adverse Reactions

The most common adverse events (all grades,> 10%) in subjects treated with LIVTENCITY were taste disturbance, nausea, diarrhea, vomiting, and fatigue.

INDICATION

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