Takeda Receives Positive CHMP Opinion for Maribavir for the Treatment of Adults with Post-transplant Cytomegalovirus (CMV) Refractory (With or Without Resistance) to Prior Therapies
− 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
“Post-transplant care is critical for transplant recipients, and CMV infection can jeopardize successful outcomes for patients,” said
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
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
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
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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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2. Avery R, et al. Maribavir for refractory cytomegalovirus infections with or without resistance post-transplant: results from a phase 3 randomized clinical trial. Clinical Infectious Diseases. 2022;75(4): 690–701.
3. Ramanan P, Razonable RR. Cytomegalovirus infections in solid organ transplantation: a review. Infection & Chemotherapy. 2013;45(3):260.
4. Camargo JF, Komanduri KV. Emerging concepts in cytomegalovirus infection following hematopoietic stem cell transplantation. Hematology/Oncology and Stem Cell Therapy. 2017;10(4):233-238.
5. Azevedo L, et al. Cytomegalovirus infection in transplant recipients. Clinics. 2015;70(7):515-523.
6. Styczynski J. Who is the patient at risk of cmv recurrence: a review of the current scientific evidence with a focus on hematopoietic cell transplantation. Infect Dis Ther. 2018;7:1-16.
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.
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.