This is an inflection year for Takeda's pipeline with up to six regulatory submissions and four potential approvals anticipated by the end of fiscal year 2021. The maribavir NDA acceptance is Takeda's fourth new molecular entity accepted for regulatory review in six months, following the FDA submissions of TAK-721 for the treatment of eosinophilic esophagitis, mobocertinib for the treatment of EGFR Exon20 insertion mutation positive metastatic non-small cell lung cancer, and the
'CMV is one of the most common viral infections experienced by transplant recipients, and current antiviral treatment options are limited, and physicians have to engage in a careful balance of viral clearance and side effect management that can impact patient care and transplant outcomes,' said
The application is based on the pivotal Phase 3 TAK-620-303 (SOLSTICE) trial, results of which were presented at the 2021 Transplantation & Cellular Therapy (TCT) Meetings Digital Experience, with subgroup analysis presented during the Presidential Symposium 47th Annual Meeting of the
'CMV infection puts transplant recipients at an increased risk of disease, such as pneumonia or gastrointestinal disease. It can also increase the risk of graft rejection, opportunistic co-infections, and in some cases, even death,' said
Maribavir has been granted Orphan Drug Designation by the FDA for treatment of clinically significant CMV viremia and disease in at-risk patients. The FDA has also granted maribavir Breakthrough Therapy Designation as a treatment for CMV infection and disease in transplant patients resistant or refractory to prior therapy. These designations do not guarantee that the FDA will approve maribavir for the treatment of CMV infections in transplant patients, and the timing of any such approval is uncertain.
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.2 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.10,11 Existing therapies to treat posttransplant CMV infections may demonstrate serious side effects that require dose adjustments or may fail to adequately suppress viral replication.12-14 Additionally, existing therapies may require or prolong hospitalization due to administration.12,13
About Maribavir
Maribavir, an orally bioavailable anti-CMV compound, is the only antiviral agent presently in Phase 3 development for the treatment of post-transplant patients with CMV in SOT or HCT. Maribavir is an investigational treatment that has not been approved for use by the
Maribavir has been granted Orphan Drug Designation by the
About Takeda's SOLSTICE Trial
The TAK-620-303 (SOLSTICE) trial (NCT02931539) is a multicenter, randomized, open-label, active-controlled trial comparing treatment with either maribavir or investigator assigned treatment, IAT, (conventional antiviral therapy) in 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. Patients underwent a 2-week screening period, followed by randomization 2:1 to maribavir (n=235) (400 mg) or IAT (n=117) for an 8-week treatment period, plus 12 weeks of follow-up.
The trial's primary endpoint was defined as the proportion of patients
Resistant defined as refractory CMV and documentation of >1 CMV genetic mutations associated with resistance to ganciclovir, valganciclovir, foscarnet, and/or cidofovir
References
1 Marty F. A Phase 3 Randomized Study of Maribavir (MBV) Versus Investigator-Assigned Antiviral Therapy (IAT) for the Treatment (Tx) of Refractory/Resistant (R/R) Cytomegalovirus (CMV) Infection in Hematopoietic Cell Transplant (HCT) or Solid Organ Transplant (SOT) Recipients. In: The 2021 TCT Meetings Digital Experience. ; 2021.
2 Krech U. Complement-fixing antibodies against cytomegalovirus in different parts of the world. Bull
3 de la Hoz R. Diagnosis and treatment approaches to CMV infections in adult patients.
4 Azevedo L, Pierrotti L, Abdala E, et al. Cytomegalovirus infection in transplant recipients. Clinics. 2015;70(7):515-523. doi:10.6061/clinics/2015(07)09
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11 Kenyon M, Babic A, eds. The European Blood and Marrow Transplantation Textbook for Nurses.
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13 Chemaly RF, Chou S, Einsele H, 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. doi:10.1093/cid/ciy696
14 Beyer K. Outpatient Foscarnet Administration Incorporating Home Infusions Is Feasible Greatly Enhancing the Care of Hematopoietic Stem Cell Transplant Recipients. Biol Blood Marrow Transplant. 2017;23:S18-S391.
15 Hamirally S, Kamil JP, Ndassa-Colday YM, et al. Viral Mimicry of Cdc2/Cyclin-Dependent Kinase 1 Mediates Disruption of Nuclear Lamina during Human Cytomegalovirus Nuclear Egress. Nelson JA, ed. PLoS Pathog. 2009;5(1):e1000275. doi:10.1371/journal.ppat.1000275
16 Krosky PM, Baek M-C, Coen DM. The Human Cytomegalovirus UL97 Protein Kinase, an Antiviral Drug Target, Is Required at the Stage of Nuclear Egress. JVI. 2003;77(2):905-914. doi:10.1128/JVI.77.2.905-914.2003
17 Prichard MN. Function of human cytomegalovirus UL97 kinase in viral infection and its inhibition by maribavir: Human cytomegalovirus UL97 kinase. Rev Med Virol. 2009;19(4):215-229. doi:10.1002/rmv.615
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