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 Most Common and Serious Post-transplant Infections and Can Lead to Loss of Transplanted Organ and Failure of Graft ^3,4

OSAKA, Japan & CAMBRIDGE, Mass.–(BUSINESS WIRE)–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.

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.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

About Maribavir

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 LIVTENCITY^TM, 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

About Takeda

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.

Important Notice

For the purposes of this notice, “press release” means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) regarding this release. This press release (including any oral briefing and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction. No shares or other securities are being offered to the public by means of this press release. No offering of securities shall be made in the United States except pursuant to registration under the U.S. Securities Act of 1933, as amended, or an exemption therefrom. This press release is being given (together with any further information which may be provided to the recipient) on the condition that it is for use by the recipient for information purposes only (and not for the evaluation of any investment, acquisition, disposal or any other transaction). Any failure to comply with these restrictions may constitute a violation of applicable securities laws. The companies in which Takeda directly and indirectly owns investments are separate entities. In this press release, “Takeda” is sometimes used for convenience where references are made to Takeda and its subsidiaries in general. Likewise, the words “we”, “us” and “our” are also used to refer to subsidiaries in general or to those who work for them. These expressions are also used where no useful purpose is served by identifying the particular company or companies.

Forward-Looking Statements

This press release and any materials distributed in connection with this press release may contain forward-looking statements, beliefs or opinions regarding Takeda’s future business, future position and results of operations, including estimates, forecasts, targets and plans for Takeda. Without limitation, forward-looking statements often include words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could” “anticipates”, “estimates”, “projects” or similar expressions or the negative thereof. These forward-looking statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those expressed or implied by the forward-looking statements: the economic circumstances surrounding Takeda’s global business, including general economic conditions in Japan and the United States; competitive pressures and developments; changes to applicable laws and regulations, including global health care reforms; challenges inherent in new product development, including uncertainty of clinical success and decisions of regulatory authorities and the timing thereof; uncertainty of commercial success for new and existing products; manufacturing difficulties or delays; fluctuations in interest and currency exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; the impact of health crises, like the novel coronavirus pandemic, on Takeda and its customers and suppliers, including foreign governments in countries in which Takeda operates, or on other facets of its business; the timing and impact of post-merger integration efforts with acquired companies; the ability to divest assets that are not core to Takeda’s operations and the timing of any such divestment(s); and other factors identified in Takeda’s most recent Annual Report on Form 20-F and Takeda’s other reports filed with the U.S. Securities and Exchange Commission, available on Takeda’s website at: https://www.takeda.com/investors/sec-filings/ or at www.sec.gov. Takeda does not undertake to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results or statements of Takeda in this press release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results.

Medical information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

*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

1. Avram S, et al. Novel drug targets in 2021. Nature Reviews Drug Discovery. 2022;21(5):328-328.

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. 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.

Contacts

Media:

Japanese Media
Jun Saito

jun.saito@takeda.com

U.S. Media
Erin-Marie Beals
erin-marie.beals@takeda.com
+1 781-336-9417

International Media
Abhi Basu
abhi.basu@takeda.com
+1 813-943-4425