FDA Advisory Committee Recommends Use of Investigational Drug Maribavir (TAK-620) to Treat Post-Transplant Recipients with Cytomegalovirus (CMV) Infection and Disease Refractory to Treatment With or Without Resistance

(BUSINESS WIRE) -- Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced the U.S. Food and Drug Administration (FDA) Antimicrobial Drugs Advisory Committee (AMDAC) voted unanimously to recommend use of maribavir (TAK-620) for the treatment of refractory cytomegalovirus (CMV) infection and disease with genotypic resistance to ganciclovir, valganciclovir, foscarnet or cidofovir in transplant recipients. The committee also voted unanimously to recommend use of maribavir for the treatment of refractory CMV infection and disease without genotypic resistance to ganciclovir, valganciclovir, foscarnet or cidofovir in transplant recipients. Both recommendations were based on the results of the Phase 2 and Phase 3 TAK-620-303 (SOLSTICE) trials.

“Today’s vote in favor of our investigational antiviral drug marks a significant step towards delivering the first approved treatment for adult transplant recipients with refractory CMV infection and disease, with or without resistance,” said Obi Umeh, MD, Vice President and Maribavir Global Program Leader at Takeda. “We look forward to working with the FDA as it completes its review of our application.”

AMDAC also heard from patients, advocates, and healthcare providers in the public forum discussion who underscored the need for new treatment options for this patient population.

The New Drug Application (NDA) for maribavir is currently under Priority Review by the FDA. The FDA will consider the vote as part of its review of the NDA and is not bound by the AMDAC’s recommendation. The NDA submission is based on the pivotal Phase 3 TAK-620-303 (SOLSTICE) trial.

“The treatment of CMV in patients who have undergone a solid organ or stem cell transplant is complicated, especially in patients who have failed standard treatment and who may be at risk for side effects from currently available medications,” said Dr. Emily Blumberg, Director, Transplant Infectious Diseases, Penn Medicine. "I am excited about the potential for an additional treatment option for post-transplant patients with 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.¹ 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).^2,3 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.^3–10

In transplant recipients, reactivation of CMV can lead to serious consequences, including loss of the transplanted organ and, in extreme cases, can be fatal.^11,12 Existing therapies to treat post-transplant CMV infections may demonstrate toxicities that require dose adjustments or may fail to adequately suppress viral replication.^11–13 Additionally, existing therapies may require or prolong hospitalization due to administration.^11,12

About maribavir

Maribavir, an orally bioavailable anti-CMV compound, is the only antiviral agent presently in Phase 3 development for the treatment of adult post-transplant patients with CMV in SOT or HSCT. Maribavir is an investigational treatment that has not been approved for use by the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), or any other regulatory authorities. Maribavir is the only CMV antiviral drug that targets and inhibits the UL97 protein kinase and its natural substrates.^14–17

Maribavir has been granted Orphan Drug Designation by the European Commission as a treatment of CMV disease in patients with impaired cell mediated immunity and by the FDA for treatment of clinically significant CMV viremia and disease in at-risk patients. Orphan status is granted to certain investigational medicines intended for the treatment or prevention of a rare, life-threatening disease. 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. Breakthrough Therapy Designation expedites the development and review of investigational treatments for serious conditions with preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over available therapy. Most recently, the FDA has granted priority review of maribavir for the treatment of adult post-transplant recipients with CMV infection in those resistant and/or refractory to prior anti-CMV treatment. These designations and NDA acceptance do not guarantee that the EMA or FDA will approve maribavir for the treatment of CMV infections in adult transplant patients, and the timing of any such approval is uncertain.

About Takeda Pharmaceutical Company Limited

Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE: TAK) 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. For more information, visit https://www.takeda.com.

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^* The difference in proportion of responders between treatment groups was obtained using Cochran-Mantel-Haenszel (CMH) weighted average across all strata and tested using stratum-adjusted CMH method, with transplant type and baseline plasma CMV DNA concentration as two stratification factors
^† Refractory defined as documented failure to achieve >1 log10 decrease in CMV DNA level in whole blood or plasma after a 14 day or longer treatment period with IV ganciclovir/oral valganciclovir, IV foscarnet, or IV cidofovir
^‡ Resistant defined as refractory CMV and documentation of >1 CMV genetic mutations associated with resistance to ganciclovir, valganciclovir, foscarnet, and/or cidofovir

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1. Krech U. Complement-fixing antibodies against cytomegalovirus in different parts of the world. Bull WHO. 1973;49:103-106.
2. de la Hoz R. Diagnosis and treatment approaches to CMV infections in adult patients. J Clin Virol. 2002;25:S1-S12.
3. 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.
4. World Health Organization. International Report on Organ Donation and Transplantation Activities- Executive Summary 2018.; 2020. Accessed December 2, 2020. http://www.transplant-observatory.org/wp-content/uploads/2020/10/glorep2018-2.pdf.
5. World Health Organization. Haematopoietic Stem Cell Transplantation HSCtx. Accessed December 2, 2020. https://www.who.int/transplantation/hsctx/en/.
6. Razonable RR, Eid AJ. A Viral infections in transplant recipients. Minerva Med. 2009;100(6):23.
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. Cho S-Y, Lee D-G, Kim H-J. Cytomegalovirus Infections after Hematopoietic Stem Cell Transplantation: Current Status and Future Immunotherapy. Int J Mol Sci. 2019;20(2666):1-17.
9. Fishman JA. Infection in Solid-Organ Transplant Recipients. N Engl J Med. Published online 2007:14.
10. 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.
11. Martín-Gandul C, Pérez-Romero P, González-Roncero FM, et al. Clinical impact of neutropenia related with the preemptive therapy of CMV infection in solid organ transplant recipients. J Infect. 2014;69(5):500-506. doi:10.1016/j.jinf.2014.07.001.
12. 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.
13. Beyer K. Outpatient Foscarnet Administration Incorporating Home Infusions Is Feasible Greatly Enhancing the Care of Hematopoietic Stem Cell Transplant Recipients. Biol Blood Marrow Transpl. 2017;23:S18-S391.
14. Abdel-Magid AF. New Inhibitors of Cytomegalovirus DNA Polymerase. ACS Med Chem Lett. 2013;4(12):1129-1130. doi:10.1021/ml4004099.
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. Kotton CN, Kumar D, Caliendo AM, et al. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation: Transplantation. 2018;102(6):900-931. doi:10.1097/TP.0000000000002191.
17. 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. J Virol. 2003;77(2):905-914. doi:10.1128/JVI.77.2.905-914.2003.
18. HRSA. Donation and Transplantation Statistics. Accessed March 9, 2021. https://bloodstemcell.hrsa.gov/data/donation-and-transplantation-statistics#:~:text=A%20total%20of%2022%2C863%20HCTs,22%25)%20were%20unrelated%20transplants

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