European Commission (EC) Approves LIVTENCITYTM

LIVTENCITY Is the First and Only Treatment Approved for This Indication by the EC1

CMV Is One of the Most Common and Serious Post-transplant Infections and Can Lead to Loss of Transplanted Organ and Failure of Graft 2,3

OSAKA, Japan & CAMBRIDGE, Mass. -- (BUSINESS WIRE) --  Takeda (TSE:4502/NYSE:TAK) today announced that the European Commission (EC) has granted Marketing Authorization for LIVTENCITYTM (maribavir) 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 adult patients who have undergone a haematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT).4 LIVTENCITY is the first and only oral treatment that inhibits CMV-specific UL97 protein kinase and its natural substrates.1  CMV is one of the most common infections experienced by transplant patients with a global estimated incidence rate of 16-56% in SOT and 30-80% in HSCT recipients.5,6 More than 34,000 SOTs,7 including liver, kidney, and heart transplant, and more than 48,000 HSCTs8 were performed in Europe and neighboring countries in 2019. Although prevention and management of CMV infection in SOT and HSCT patients with available therapies may help improve outcomes,5 breakthrough infections can still occur with prophylaxis,9 and some CMV infections may not respond to treatment.10  “The European Society for Organ Transplantation (ESOT) understands that the transplant patient journey extends well beyond the transplant itself. When not successfully treated, CMV poses a challenge to transplant recipients and their physicians and often leads to increased organ rejection, higher hospitalization rates, and greater burden on healthcare resources, contributing to inequities for patients across the system,” said Dr. Luciano Potena, ESOT President. “The approval of LIVTENCITY by the EC recognizes the need for a new antiviral approach for managing CMV infection that is refractory (with or without resistance) to one or more prior CMV therapies.”  The centralized marketing authorization is valid in all EU member states as well as in Iceland, Liechtenstein, Norway, and Northern Ireland, and was based on the Phase 3 SOLSTICE trial, which evaluated the safety and efficacy of LIVTENCITY versus conventional antiviral therapies—ganciclovir, valganciclovir, cidofovir or foscarnet—for the treatment of adult HSCT and SOT recipients with CMV infection refractory (with or without resistance) to prior therapies.  The EC approval marks the fourth approval of LIVTENCITY for post-transplant refractory (with or without resistance) CMV infection, following the U.S., Canada, and Australia.13-15  “Patients who receive a transplant can face a difficult journey on the road to recovery that involves medicines to suppress their immune system. The additional burden of a CMV infection that has become refractory to treatment, and which could threaten their transplant, poses a challenge to patients being offered a second chance at life,” said Ramona Sequeira, President, Global Portfolio Division, Takeda. “With the EC approval of LIVTENCITY, we are privileged to offer healthcare providers in the EU and EEA* with an additional oral antiviral treatment for post-transplant refractory CMV.”  About CMV  CMV is a beta herpesvirus that commonly infects humans; serologic evidence of prior infection can be found in 40-100% of various adult populations.14 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 who receive immunosuppressants associated with various types of transplants including HSCT or SOT.5 Out of the estimated 200,000 adult transplants per year globally, CMV is one of the most common viral infections experienced by transplant recipients, with an estimated incidence rate between 16-56% in SOT recipients and 30-80% in HSCT recipients.5,6  In transplant recipients, reactivation of CMV can lead to serious consequences including loss of the transplanted organ and, in extreme cases, can be fatal.2,3 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.10 Additionally, existing therapies may require or prolong hospitalization due to administration.10,15  About LIVTENCITY  LIVTENCITYTM (maribavir), an orally bioavailable anti-CMV compound, is the first and only antiviral agent that targets and inhibits the UL97 protein kinase and its natural substrates.16 It is approved by the U.S. Food and Drug Administration for the treatment of adults and pediatric patients (12 years of age or older and weighing at least 35 kg) with post-transplant CMV infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir, or foscarnet.12 It is approved by the EC for the treatment of 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 adult patients who have undergone a HSCT or SOT.4 It is also approved by Health Canada for the treatment of adults with post-transplant cytomegalovirus (CMV) infection/disease who are refractory (with or without genotypic resistance) to one or more prior antiviral therapies.11 LIVTENCITY is also approved in Australia for the treatment of adults with post-transplant CMV infection and disease resistant, refractory, or intolerant to one or more prior therapies.13  Product name LIVTENCITY 200 mg film coated tablets.  Generic name Maribavir  Indications and effects LIVTENCITY 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 adult patients who have undergone a haematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT).     Consideration should be given to official guidance on the appropriate use of antiviral agents.  Posology and Administration LIVTENCITY should be initiated by a physician experienced in the management of patients who have undergone solid organ transplant or haematopoietic stem cell transplant.  Posology: The recommended dose of LIVTENCITY is 400 mg (two 200 mg tablets) twice daily resulting in a daily dose of 800 mg for 8 weeks. Treatment duration may need to be individualised based on the clinical characteristics of each patient.  Paediatric population: The safety and efficacy of LIVTENCITY in patients below 18 years of age have not been established. No data are available.  Method of administration: Oral use.  LIVTENCITY is intended for oral use only and can be taken with or without food. The film coated tablet can be taken as a whole tablet, a crushed tablet, or a crushed tablet through a nasogastric or orogastric tube.  About Takeda’s SOLSTICE Trial  The TAK-620-303 (SOLSTICE) trial (NCT02931539, EudraCT 2015-004725-13) was a global, multicenter, randomized, open-label, active-controlled superiority trial to assess the efficacy and safety of treatment with either maribavir or conventional antiviral therapy in 352 haematopoietic stem cell transplant and solid organ transplant recipients with CMV infection refractory, with or without resistance, to one or a combination ofthe conventional antiviral therapies: ganciclovir, valganciclovir, foscarnet, or cidofovir. Adult patients underwent a 2-week screening period, followed by randomization 2:1 to maribavir (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.16  The trial’s primary efficacy 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 16.16  About Takeda  Takeda is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to discover and deliver life-transforming treatments, guided by our commitment to patients, our people and the planet. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience, and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people’s lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions. For more information, visit https://www.takeda.com.  LIVTENCITY Safety Information for Europe  Please consult the LIVTENCITY