− If Approved, Maribavir Would be the First and Only Inhibitor of CMV-specific UL97 Protein Kinase in the EU for Treatment of Adults with Post-transplant CMV Refractory (With or Without Resistance) to Prior Therapies1
− Positive Opinion Based on Phase 3 SOLSTICE Study Demonstrating Maribavir Was Statistically Superior to Conventional Therapies at Study Week 8, for Primary Endpoint2
− CMV is One of the Most Common and Serious Post-transplant Infections and Can Lead to Loss of Transplanted Organ and Failure of Graft 3,4
Takeda(TSE:4502/NYSE:TAK) today announced the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of 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 hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT).
The European Commission (EC) will consider the CHMP positive opinion and decide upon potential marketing authorization in the coming months. If approved, maribavir would be the first inhibitor of CMV-specific UL97 protein kinase in the European Union (EU) for this indication.1 The positive opinion from the CHMP was based on the SOLSTICE trial, which evaluated the safety and efficacy of maribavir versus conventional antiviral therapies—ganciclovir, valganciclovir, foscarnet or cidofovir—for the treatment of patients with CMV infection refractory, with or without resistance.
“Post-transplant care is critical for transplant recipients, and CMV infection can jeopardize successful outcomes for patients,” said Daniel Curran, Head, Rare Diseases Therapeutic Area, Takeda. “The CHMP positive opinion on the marketing authorization of maribavir is a positive step toward redefining the CMV treatment landscape for transplant patients and their healthcare providers across Europe and toward addressing a great unmet need for this community.”
CMV is one of the most common infections experienced by transplant patients, with a global estimated incidence rate of 16%–56% in SOT recipients and 30%–70% in HSCT recipients.5,6 More than 34,000 SOTs 7 and more than 48,000 HSCTs 8 were performed in Europe and neighboring countries in 2019.
CMV is a beta herpesvirus that commonly infects humans; serologic evidence of prior infection can be found in 40%-100% of various adult populations.9 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 30-70% 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.3,4 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.10,11
Maribavir, an orally bioavailable anti-CMV compound, is the first and only antiviral agent that targets and inhibits the pUL97 protein kinase and its natural substrates.1
In November 2021, maribavir received U.S. Food and Drug Administration (FDA) approval, under the brand name LIVTENCITYTM, for the treatment of adults and pediatric patients (12 years of age or 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. In addition to awaiting a final European Commission decision, regulatory filings are underway with other health authorities worldwide.
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 hematopoietic stem 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 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.2
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 16.2
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.
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*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 who were asymptomatic at baseline
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5. Azevedo L, et al. Cytomegalovirus infection in transplant recipients. Clinics. 2015;70(7):515-523.
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7. Vanholder, R, et al. Organ donation and transplantation: a multi-stakeholder call to action. Nature Reviews Nephrology. 2021;17:554-568.
8. Passweg JR, et al. Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years. Bone Marrow Transplant. 2021;56(7):1651-1664.
9. de la Hoz R. Diagnosis and treatment approaches to CMV infections in adult patients. Journal of Clinical Virology. 2002;25:1-12.
10. Chemaly RF, et al. Definitions of resistant and refractory cytomegalovirus infection and disease in transplant recipients for use in clinical trials. Clinical Infectious Diseases. 2019;68(8):1420-1426.
11. Martín-Gandul C, et al. Clinical impact of neutropenia related with the preemptive therapy of CMV infection in solid organ transplant recipients. Journal of Infection. 2014;69(5):500-506.
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