Health Canada approves Takeda's LIVTENCITY™ (maribavir) the First and Only Treatment for Adults with Post-Transplant Cytomegalovirus (CMV) infection

TORONTO, Sept. 20, 2022 /CNW/ - Takeda Canada Inc. ("Takeda") is pleased to announce that Health Canada has authorized (Notice of Compliance) LIVTENCITY™ (maribavir) 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.¹ Compared to conventionally used antivirals to treat post-transplant CMV, LIVTENCITY offers twice the efficacy¹ and more than 10 times less toxicity.^1*

LIVTENCITY was evaluated using the Health Canada priority review process which recognizes the significant unmet need for this patient population. The Canadian approval of LIVTENCITY represents the second market globally to receive authorization for this important CMV treatment.

"Health Canada's authorization of LIVTENCITY represents a much-needed treatment option for post-transplant patients with refractory/resistant CMV infection or disease," said Dr. Shariq Haider, Professor of Medicine McMaster University Division of Infectious Disease and General Medicine and Research Lead Transplant Malignant ID Juravinski Hospital and Cancer Center, Hamilton ON. "Until now, physicians have relied upon conventional non-indicated antiviral therapies as the only option to treat post-transplant CMV which can be difficult to manage post-transplant. The addition of an effective oral treatment for CMV, with a better safety profile, is welcome news for Canadian patients, physicians and the transplant community."

The approval of LIVTENCITY is based on the SOLSTICE Study which assessed the efficacy and safety of LIVTENCITY treatment compared to Investigator Assigned Treatment (IAT) in 350 Hematopoietic Stem Cell Transplant (HSCT) and Solid Organ Transplant (SOT) recipients with CMV infections that were refractory to treatment with ganciclovir, valganciclovir, foscarnet, or cidofovir, including CMV infections with or without confirmed resistance to 1 or more anti-CMV agents.¹ Beneficial treatment effect was consistent regardless of transplant type, baseline CMV DNA viral load, genotypic resistance, CMV syndrome at baseline and age.¹

"A diagnosis of CMV infection can be particularly unsettling for patients given the complex challenges associated with receiving a life-saving transplant," said Rute Fernandes, General Manager, Takeda, Canada. "Providing patients with the first indicated post-transplant CMV treatment underscores Takeda's commitment to finding solutions for patients where there is an unmet need, and we look forward to working with the appropriate agencies to bring LIVTENCITY to Canadians."

Current antiviral treatment options for post-transplant cytomegalovirus (CMV) infections have unfavorable toxicities, such as neutropenia or nephrotoxicity, that may impact patient care and transplant outcomes.²

About LIVTENCITY

LIVTENCITY, is a selective orally bioavailable benzimidazole riboside antiviral drug with a novel mechanism of action against human CMV (HCMV). LIVTENCITY attaches to the UL97 encoded kinase at the adenosine triphosphate (ATP) binding site, abolishing phosphotransferase needed in processes such as DNA replication, encapsidation, and nuclear egress of viral capsids.¹

The recommended dose of LIVTENCITY is 400 mg (two 200 mg tablets) twice daily resulting in a daily dose of 800 mg.¹ LIVTENCITY is intended for oral use only and can be taken with or without food.¹

The primary efficacy endpoint was confirmed CMV viremia clearance (plasma CMV DNA concentration below the lower limit of quantification (<LLOQ; i.e., <137 IU/mL)) at Week 8. The key secondary endpoint was CMV viremia clearance and CMV infection symptom control at the end of Study Week 8 with maintaining this treatment effect through Study Week 16.¹

For the primary endpoint, LIVTENCITY was superior to IAT (56% vs. 24%, respectively, p<0.001). For the key secondary endpoint, 19% vs. 10% achieved both CMV viremia clearance and CMV infection symptom control in the LIVTENCITY and IAT group, respectively (p=0.013).¹

Most common adverse reactions with LIVTENCITY were: taste disturbance (44.8%), nausea (8.5%), vomiting (7.7%), immunosuppressant drug concentration level increased (6.4%), diarrhea (3.8%), abdominal pain (2.1%), neutropenia (1.7%), acute kidney injury (1.7%), anemia (1.3%), and decreased appetite (1.3%).¹

Serious adverse events (SAEs) occurred less frequently in the LIVTENCITY group than in the IAT group (5.1% and 14.7%, respectively).¹

No patients in the LIVTENCITY group experienced serious, drug-related neutropenia or febrile neutropenia.¹

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.³ 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 hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT).^4,5 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.^6,7,8,9

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 post-transplant CMV infections may demonstrate serious side effects that require dose adjustments or may fail to adequately suppress viral replication.^{12,13,14,15,16}  Additionally, existing therapies may require or prolong hospitalization due to intravenous administration, side effect management and monitoring for adequate hydration.¹⁰

About Takeda Canada Inc.

Takeda Canada Inc. is the Canadian organization of Takeda Pharmaceutical Company Limited (TSE: 4502) (NYSE: TAK), a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to discovering and delivering 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: takeda.com/en-ca

References

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^1	LIVTENCITY™ Product Monograph. September 15, 2022
^2	Maffini E, et al. Expert Rev Hematol. 2016;9:585-96; Stevens DR, et al. Transpl Infect Dis. 2015;17:163–73
^3	de la Hoz R. Diagnosis and treatment approaches to CMV infections in adult patients. J Clin Virol. 2002;25:S1-S12.
^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.
^5	Razonable RR, Eid AJ. A Viral infections in transplant recipients. Minerva Med. 2009;100(6):23.
^6	Shannon-Lowe & Emery. The effects of maribavir on the autophosphorylation of ganciclovir resistant mutants of the cytomegalovirus UL97 protein. Herpesviridae 2010, 1:4.
^7	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 Ther. 2018;7:1-16.
^8	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.
^9	World Health Organization. Haematopoietic Stem Cell Transplantation HSCtx. Accessed December 2, 2020. https://www.who.int/transplantation/hsctx/en/.
^10	de la Hoz R. Diagnosis and treatment approaches to CMV infections in adult patients. J Clin Virol. 2002;25:S1-S12.
^11	Kenyon M, Babic A, eds. The European Blood and Marrow Transplantation Textbook for Nurses. Springer International Publishing; 2018. doi:10.1007/978-3-319-50026-3.
^12	El Chaer et al. How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients. Blood, 2016
^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. Clin Infect Dis. 2019;68(8):1420-1426. doi:10.1093/cid/ciy696.
^14	Razonable RR, Eid AJ. A Viral infections in transplant recipients. Minerva Med. 2009;100(6):23.
^15	Ljungman et al. Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL7).Lancet Vol.19, Aug 2019.
^16	Razonable & Humar. Cytomegalovirus in solid organ transplant recipients— Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clinical Transplantation, Feb 2019.
*	Refers to acute kidney injury related to foscarnet and neutropenia related to valganciclovir/ganciclovir

SOURCE Takeda Canada Inc.

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