RegulationPriority Review (US), Breakthrough Therapy (US), Fast Track (US), Orphan Drug (US), Orphan Drug (EU), Priority Review (CN), Breakthrough Therapy (CN), Orphan Drug (JP), Orphan Drug (AU), Priority Review (AU)

Structure

Molecular FormulaC15H19Cl2N3O4

InChIKeyKJFBVJALEQWJBS-XUXIUFHCSA-N

CAS Registry176161-24-3

Clinical Trials associated with Maribavir

NCT06439342 / Not yet recruitingPhase 3

An Open-label, Single-arm Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of Maribavir in Chinese Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Cidofovir or Foscarnet

The main aim of this study is to learn how safe maribavir is in Chinese adults who have undergone hematopoietic stem cell or organ transplantation and have a cytomegalovirus (CMV) infection and how well they tolerate treatment with maribavir. Other aims are to see how effective maribavir is in treating CMV infection and getting rid of the symptoms, the recurrence rate of CMV infection after treatment with maribavir and if the treatment is required again. Researchers will also check for changes (mutations) occurring in the virus which may cause treatment with maribavir to no longer work well or to not work at all (resistance to maribavir).
The participants will be treated with maribavir for 8 weeks.
During the study, participants will visit their study clinic 18 times.

Start Date14 Mar 2025

Sponsor / Collaborator

Takeda Pharmaceutical Co., Ltd.

CTR20234262 / CompletedNot Applicable

马立巴韦片在健康受试者中随机、开放、两制剂、单次给药、两周期、双交叉空腹和餐后状态下的生物等效性试验

[Translation] A randomized, open-label, two-dose, single-dose, two-period, double-crossover bioequivalence study of maribavir tablets in healthy subjects under fasting and fed conditions

主要目的：以桂林南药股份有限公司生产的马立巴韦片为受试制剂，以Takeda Pharmaceuticals USA, Inc生产，桂林南药股份有限公司提供的马立巴韦片（商品名：LIVTENCITY®）为参比制剂，考察两制剂在空腹及餐后状态下单次给药的药代动力学参数及相对生物利用度，评价两制剂是否具有生物等效性。次要目的：评价中国健康受试者单次空腹/餐后口服马立巴韦片受试制剂和参比制剂后的安全性。

[Translation]

Primary objective: To use Maribavir Tablets produced by Guilin Pharmaceutical Co., Ltd. as the test preparation and Maribavir Tablets (trade name: LIVTENCITY®) produced by Takeda Pharmaceuticals USA, Inc and provided by Guilin Pharmaceutical Co., Ltd. as the reference preparation, to investigate the pharmacokinetic parameters and relative bioavailability of the two preparations in the fasting and postprandial state after a single administration, and to evaluate whether the two preparations are bioequivalent. Secondary objective: To evaluate the safety of the test and reference preparations of Maribavir Tablets after a single oral administration on an empty stomach/postprandial basis in healthy Chinese subjects.

Start Date22 Jan 2024

Sponsor / Collaborator

Guilin Pharmaceutical Co., Ltd.

NCT05319353 / RecruitingPhase 3

A Phase 3, Open-label, Single-arm, Repeated-dose Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Antiviral Activity of Maribavir for the Treatment of Cytomegalovirus (CMV) Infection in Children and Adolescents Who Have Received a Hematopoietic Stem Cell Transplant (HSCT) or a Solid Organ Transplant (SOT)

The main aim of this study is to find out the safety, tolerability and pharmacokinetics (PK) of maribavir for the treatment of CMV infection in children and teenagers after HSCT or SOT and to identify the optimal dose of maribavir using a 200 milligrams (mg) adult tablet formulation or other formulation based on PK modeling.
The participants will be treated with maribavir for 8 weeks.
Participants need to visit their doctor during 12-week follow-up period.

Start Date13 Nov 2023

Sponsor / Collaborator

Takeda Pharmaceutical Co., Ltd.

[+1]

100 Clinical Results associated with Maribavir

100 Translational Medicine associated with Maribavir

100 Patents (Medical) associated with Maribavir

189

Literatures (Medical) associated with Maribavir

14 Feb 2024·The Journal of infectious diseases

Drug Resistance Assessed in a Phase 3 Clinical Trial of Maribavir Therapy for Refractory or Resistant Cytomegalovirus Infection in Transplant Recipients

Article

Author: Buss, Neil E ; Fournier, Martha ; Cervera, Carlos ; Chemaly, Roy F ; Chou, Sunwen ; Lundgren, Jens ; Alain, Sophie ; Murray, Rose Ann ; Kotton, Camille N ; Wu, Jingyang J ; Pereira, Marcus R ; Papanicolaou, Genovefa A

Abstract:

Background:

This drug resistance analysis of a randomized trial includes 234 patients receiving maribavir and 116 receiving investigator-assigned standard therapy (IAT), where 56% and 24%, respectively, cleared cytomegalovirus DNA at week 8 (treatment responders).

Methods:

Baseline and posttreatment plasma samples were tested for mutations conferring drug resistance in viral genes UL97, UL54, and UL27.

Results:

At baseline, genotypic testing revealed resistance to ganciclovir, foscarnet, or cidofovir in 56% of patients receiving maribavir and 68% receiving IAT, including 9 newly phenotyped mutations. Among them, 63% (maribavir) and 21% (IAT) were treatment responders. Detected baseline maribavir resistance mutations were UL27 L193F (n = 1) and UL97 F342Y (n = 3). Posttreatment, emergent maribavir resistance mutations were detected in 60 (26%) of those randomized to maribavir, including 49 (48%) of 103 nonresponders and 25 (86%) of the 29 nonresponders where viral DNA initially cleared then rebounded while on maribavir. The most common maribavir resistance mutations were UL97 T409M (n = 34), H411Y (n = 26), and C480F (n = 21), first detected 26 to 130 (median 56) days after starting maribavir.

Conclusions:

Baseline maribavir resistance was rare. Drug resistance to standard cytomegalovirus antivirals did not preclude treatment response to maribavir. Rebound in plasma cytomegalovirus DNA while on maribavir strongly suggests emerging drug resistance.

Clinical Trials Registration:

NCT02931539.

01 Feb 2024·Antiviral research

Ganciclovir and maribavir cross-resistance revisited: Relative drug susceptibilities of canonical cytomegalovirus mutants

Article

Author: Chou, Sunwen ; Watanabe, Justin

Therapeutic use of maribavir for human cytomegalovirus infection has renewed attention to the extent of cross-resistance with ganciclovir as the existing standard therapy. Each drug selects in vivo for a characteristic set of resistance mutations in the viral UL97 kinase gene. To improve the calibration of relative susceptibilities to each drug, genetic variants at relevant UL97 codons were extensively phenotyped using the same baseline viral clone, cell culture conditions and growth readout. Ganciclovir-selected mutations at codons 460, 520, 592, 594, 595 and 603 conferred 2.8-fold (C603Y) to 12-fold (M460I) increases in ganciclovir 50% inhibitory concentrations (EC50) over wild type baseline, while conferring maribavir EC50 fold changes ranging from 0.21-fold (M460I) to 1.9-fold (A594V). Maribavir-selected mutations at codons 409, 411 and 480 conferred maribavir EC50 fold changes ranging from 17 (H411Y) to 210 (C480F), while conferring ganciclovir EC50 fold changes ranging from 0.7 (H411Y) to 2.3 (C480F). The P-loop substitution F342Y, selected by either drug, is confirmed to confer 4.7-fold and 6-fold increases in maribavir and ganciclovir EC50s respectively, and suggests this part of the ATP-binding domain of UL97 to be involved in moderate resistance to both drugs. The maribavir hypersensitivity of M460I and M460V may be advantageous.

01 Jan 2024·Clinical and translational science

Maribavir: Mechanism of action, clinical, and translational science

Review

Author: Sun, Kefeng ; Fournier, Martha ; Song, Ivy H ; Sundberg, Aimee K

Abstract:

Maribavir is an oral benzimidazole riboside for treatment of post‐transplant cytomegalovirus (CMV) infection/disease that is refractory to prior antiviral treatment (with or without resistance). Through competitive inhibition of adenosine triphosphate, maribavir prevents the phosphorylation actions of UL97 to inhibit CMV DNA replication, encapsidation, and nuclear egress. Maribavir is active against CMV strains with viral DNA polymerase mutations that confer resistance to other CMV antivirals. After oral administration, maribavir is rapidly and highly absorbed (fraction absorbed >90%). The approved dose of 400 mg twice daily (b.i.d.) achieves a steady‐state area under the curve per dosing interval of 128 h*μg/mL and trough concentration of 4.90 μg/mL (13.0 μM). Maribavir is highly bound to human plasma proteins (98%) with a small apparent volume of distribution of 27.3 L. Maribavir is primarily cleared by hepatic CYP3A4 metabolism; its major metabolite, VP44669 (pharmacologically inactive), is excreted in the urine and feces. There is no clinically relevant impact on maribavir pharmacokinetics by age, sex, race/ethnicity, body weight, transplant type, or hepatic/renal impairment status. In phase II dose‐ranging studies, maribavir showed similar rates of CMV viral clearance across 400, 800, or 1200 mg b.i.d. groups, ranging from 62.5–70% in study 202 (NCT01611974) and 74–83% in study 203 (EudraCT 2010–024247‐32). In the phase III SOLSTICE trial (NCT02931539), maribavir 400 mg b.i.d. demonstrated superior CMV viremia clearance at week 8 versus investigator‐assigned treatments, with lower treatment discontinuation rates. Dysgeusia, nausea, vomiting, and diarrhea were commonly experienced adverse events among patients treated with maribavir in clinical trials.

News (Medical) associated with Maribavir

24 Jun 2024

·www.biospace.com

Takeda Announces Approval of LIVTENCITY® (maribavir) in Japan for Post-Transplant Cytomegalovirus (CMV) Infection/Disease That Is Refractory to Existing Anti-CMV Therapies

LIVTENCITY Is the First and Only Post-Transplant Anti-CMV Treatment Approved in Japan That Targets/Inhibits UL97 Protein Kinase1 CMV Is One of the Most Common and Serious Post-transplant Infections and Can Lead to Secondary Infections and Serious Consequences, Including Loss of Transplanted Organ and Failure of Graft2,3 OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Takeda (TSE:4502/NYSE:TAK) today announced that LIVTENCITY® (maribavir) has been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for post-transplant cytomegalovirus (CMV) infection/disease that is refractory to existing anti-CMV therapies.4 LIVTENCITY is the first and only post-transplant anti-CMV treatment approved in Japan that targets and inhibits pUL97 kinase and its natural substrates.1 “We are pleased by the approval of LIVTENCITY in Japan, which will provide the transplant community with a new option for treatment of post-transplant CMV infection in patients refractory to other therapies,” said Yasushi Kajii, Head, R&D Japan Region at Takeda. “A diagnosis of CMV infection can be particularly challenging for patients, and serious complications such as increased organ rejection and hospitalization rates can occur, when not successfully treated. We believe LIVTENCITY has the potential to help address the challenges faced by people with post-transplant CMV and transform the treatment landscape for patients in Japan.” The approval is primarily based on the results of the Phase 3 SOLSTICE trial (NCT02931539), which evaluated the safety and efficacy of LIVTENCITY versus alternative antiviral treatments for patients with CMV infection/disease refractory* to prior therapies who underwent hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT), and the Japanese Phase 3 open-label study in patients with CMV infection, including those with refractory* CMV infection who underwent HSCT or SOT (NCT05137717). In the SOLSTICE trial (maribavir n=235, alternative treatments n=117), maribavir showed statistically significant improvement when compared to alternative antiviral treatments at the end of Week 8 for the primary endpoint of confirmed CMV viremia clearancea in post-transplant (HSCT or SOT) adults with refractory* CMV infection.5 Of the 234 patients included in the safety evaluation, adverse reactions (related cases) were observed in 141 patients (60.3%).5 An open-label, multicenter, single-arm study was conducted to evaluate the efficacy and safety in Japanese patients in post-transplant (HSCT or SOT) adultsc (41 randomized, including 3 subjects with CMV infection refractory* to the most recently administered anti-CMV agent). The primary endpoint of CMV viremia clearanceb at the end of Study Week 8 was achieved in 33.3% of patients with refractory* CMV infection.4 Of 41 subjects included in the safety evaluation, adverse reactions (related events) were observed in 36.6% (15 subjects). 4 About LIVTENCITY LIVTENCITY (maribavir), an orally administered (tablet) anti-CMV compound, is the first and only antiviral agent that targets and inhibits the CMV-specific UL97 protein kinase and thus its natural substrates.1 As of June 2024, LIVTENCITY is approved in more than 30 countries for post-transplant CMV refractory* to prior therapies, including such major markets as Japan, the United States, Canada, Australia, the European Union and China. LIVTENCITY Product Overview in Japan Product Name LIVTENCITY 200 mg tablets. Generic Name Maribavir Indications The post-transplant cytomegalovirus (CMV) infection/disease that is refractory to existing anti-CMV therapies. Precautions concerning indications This drug should be administered to post-transplant patients with CMV infection/disease who have responded inadequately to other therapies. Efficacy and safety have not been studied in patients with CMV infection of the central nervous system and CMV retinitis. Based on nonclinical studies, this drug is expected to cross the blood-brain barrier but has low potential to enter the central nervous system. Dosage and Administration Usually, the recommended dosage for adultsc is 400 mg of maribavir to be administered orally twice daily. About Takeda’s SOLSTICE Trial The TAK-620-303 (SOLSTICE) trial (NCT02931539, EudraCT 2015-004725-13) was a Phase 3 global, multicenter, randomized, open-label, active-controlled trial to assess the efficacy and safety of maribavir treatment compared to investigator-assigned treatment (alternative antiviral therapies) in 352 HSCT and SOT recipients with CMV infections that were refractory* or resistant to one or a combination of the alternative 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 alternative antiviral treatments (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.5 The trial’s primary efficacy endpoint was confirmed CMV viremia clearance a at the end of Week 8. The key secondary endpoint was confirmed CMV viremia clearance and CMV infection symptom control† at the end of Study Week 8 with maintenance of this treatment effect through Study Week 16.5 About Cytomegalovirus (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.6 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.5,7 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 30-80% in HSCT recipients.7,8 In transplant recipients, reactivation of CMV infection can lead to secondary infections and serious consequences, including graft loss and, in extreme cases, can be fatal.2,3,5 About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit . LIVTENCITY Safety Information Contraindications Contraindications include Hypersensitivity to the active substance or to any of the excipients and co‑administration with ganciclovir or valganciclovir. Special warnings and precautions for use Some maribavir pUL97 resistance-associated substitutions confer cross-resistance to ganciclovir and valganciclovir. CMV DNA levels should be monitored, and resistance mutations should be investigated in patients who do not respond to treatment. Treatment should be discontinued if maribavir resistance mutations are detected. LIVTENCITY is not expected to be effective in treating CMV CNS infections (e.g. meningo‑encephalitis). LIVTENCITY has the potential to increase the concentrations of immunosuppressants that are cytochrome P450 (CYP)3A/P-gp substrates with narrow therapeutic margins (including tacrolimus, cyclosporine, sirolimus and everolimus). The plasma levels of these immunosuppressants must be frequently monitored throughout treatment with LIVTENCITY, especially following initiation and after discontinuation of LIVTENCITY, and doses should be adjusted, as needed. The concomitant use of LIVTENCITY and certain medicinal products may result in known or potentially significant medicinal product interactions, some of which may lead to: possible clinically significant adverse reactions from greater exposure of concomitant medicinal products. reduced therapeutic effect of LIVTENCITY. Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium‑free’. Pregnancy & Breast-feeding: LIVTENCITY is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast‑feeding should be discontinued during treatment with LIVTENCITY. Interactions Effect of other medicinal products on maribavir: Co-administration of maribavir with strong cytochrome P450 3A (CYP3A) inducers rifampicin, rifabutin or St. John’s wort is not recommended. If co-administration of maribavir with other strong or moderate CYP3A inducers (e.g., carbamazepine, efavirenz, phenobarbital and phenytoin) cannot be avoided, the maribavir dose should be increased to 1 200 mg twice daily. No dose adjustment is needed when maribavir is co‑administered with CYP3A inhibitors. Effect of maribavir on other medicinal products: If dose adjustments of concomitant medicinal products are made due to treatment with maribavir, doses should be readjusted after treatment with maribavir is completed. Co-administration of maribavir with valganciclovir and ganciclovir is contraindicated. Concomitant administration of maribavir and medicinal products that are sensitive substrates of CYP1A2 with a narrow therapeutic window (e.g., tizanidine and theophylline) should be avoided due to the risk for lack of efficacy of CYP1A2 substrates. When the immunosuppressants tacrolimus, cyclosporine, everolimus or sirolimus are co-administered with maribavir, immunosuppressant levels should be frequently monitored throughout treatment with maribavir, especially following initiation and after discontinuation of maribavir and dose adjusted, when needed. Caution should be exercised when maribavir and sensitive P-gp substrates (e.g., digoxin, dabigatran) are co‑administered. Serum digoxin concentrations should be monitored, and dose of digoxin may need to be reduced, as needed (see Table 1). Co‑administration of maribavir with sensitive BCRP substrates such as rosuvastatin, is expected to increase their exposure and lead to undesirable effects. Adverse Reactions Very common (≥1/10) Taste disturbance, Diarrhoea, Nausea, Vomiting, Fatigue Common (≥1/100 to <1/10) Headache, Abdominal pain upper, Decreased appetite, Immunosuppressant drug level increased, Weight decreased The most commonly reported serious adverse reactions were diarrhoea (2%) and nausea, weight decreased, fatigue, immunosuppressant drug level increased, and vomiting (all occurring at < 1%). Please consult the LIVTENCITY (maribavir) approved label before prescribing, particularly in relation to dosing and treatment monitoring. For Japan, please consult the LIVTENCITY Japan Package Insert. For the European Union, please consult the Summary of Products Characteristics (SmPC). For China, please consult the LIVTENCITY China Package Leaflet. For full U.S. Prescribing Information, including the approved indication and important safety information, please visit: 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: or at . 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. * Including a subgroup with genotypic resistance to alternative antiviral treatments. a Defined as confirmed CMV DNA concentration below the lower limit of quantification (<LLOQ; i.e., <137 IU/mL) in two consecutive samples separated by at least five days. b Defined as confirmed CMV DNA concentration below the lower limit of quantification (<LLOQ; i.e., <34.5 IU/mL) in two consecutive samples separated by at least five days. c Defined as > 15 years old † 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. References Avram S, et al. Novel drug targets in 2021. Nature Reviews Drug Discovery. 2022;21(5):328-328. Ramanan P, Razonable RR. Cytomegalovirus infections in solid organ transplantation: a review. Infection & Chemotherapy. 2013;45(3):260 Camargo JF, Komanduri KV. Emerging concepts in cytomegalovirus infection following hematopoietic stem cell transplantation. Hematol Oncol Stem Cell Ther. 2017;10(4):233-238. doi:10.1016/j.hemonc.2017.05.001 LIVTENCITY Package Insert in Japan. Avery R, Alain S, Alexander BD, et al. SOLSTICE Trial Investigators. Maribavir for refractory cytomegalovirus infections with or without resistance post-transplant: results from a phase 3 randomized clinical trial. Clin Infect Dis. 2022;75(4):690–701. doi:10.1093/cid/ciab988 de la Hoz RE, Stephanie G, Sherlock C. Diagnosis and treatment approaches to CMV infections in adult patients. J Clin Virol. 2002;25(Suppl 1):S1-S12. doi:10.1016/s1386-6532(02)00091-4 Azevedo LS, Pierrotti LC, Abdala E, et al. Cytomegalovirus infection in transplant recipients. Clinics (Sao Paolo). 2015;70(7):515-523. doi:10.6061/clinics/2015(07)09 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. doi:10.1007/s40121-017-0180-z View source version on businesswire.com: Contacts International Media Rand Walton rand.walton@takeda.com Japan Media Shigeyuki Matsui shigeyuki.matsui@takeda.com Source: Takeda Pharmaceutical Company Limited View this news release online at:

Clinical ResultPhase 3Drug ApprovalCell TherapyImmunotherapy

01 Feb 2024

·www.biospace.com

Takeda Announces Third-Quarter FY2023 Results; On-Track Towards Full-Year Management Guidance With Strong Momentum in Growth & Launch Products

Two New U.S. FDA Approvals in FY2023 Q3: FRUZAQLA for Adults With Previously Treated Metastatic Colorectal Cancer and ADZYNMA for Ultra-Rare Blood Clotting Disorder cTTP Strong Commercial Execution Maximizing Value of Existing Portfolio: ENTYVIO® Pen Launched in U.S. for Ulcerative Colitis; U.S. FDA Approval Decision on Crohn’s Disease Filing Expected in early FY2024 QDENGA ® Dengue Vaccine Now Launched in 21 Countries LIVTENCITY ® Approved in China for Refractory Post-Transplant CMV Revenue Growth of +4.6% at Actual Exchange Rate (AER); Flat at Constant Exchange Rate (CER) Core Operating Profit Change of -12.7% at CER, Reflecting Generic Impact, Lower Coronavirus Vaccines Revenue and Increased Investment in R&D and Data, Digital & Technology Life-Cycle Management Approvals for HYQVIA® and GAMMAGARD LIQUID® in January Support Forward Momentum of Growth & Launch Products Confirms Full-Year Management Guidance OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Takeda (TOKYO:4502/NYSE:TAK) today announced financial results for the third quarter of fiscal year 2023 (period ended December 31, 2023). With year-to-date strong momentum in its Growth & Launch Products (+12.7% at CER) offsetting the significant revenue impact of generic entrants, Takeda remains on track towards its full-year Management Guidance. Takeda chief financial officer, Costa Saroukos, commented: “In FY2023 Q3 we made further progress in our vision to discover and deliver life-transforming treatments, receiving two new U.S. FDA approvals and broadening the reach of our existing portfolio with multiple life-cycle management approvals for our Growth & Launch Products. “We remain on track towards our full-year Management Guidance at CER, reflecting significant generic impact, lower coronavirus vaccines revenue and investment in R&D and data, digital and technology to secure our long-term competitiveness, as well as continued strong momentum in our Growth & Launch Products. “We continue to improve our debt pro 100% of our debt now at fixed interest rates averaging 1.6%, and our financial foundation remains strong as we enter the fourth quarter of FY2023.” FINANCIAL HIGHLIGHTS Results for FY2023 Q3 YTD Ended December 31, 2023 (Billion yen, except percentages and per share amounts) REPORTED CORE(c) (Non-IFRS)(a) FY2023 Q3 YTD vs. PRIOR YEAR (Actual % change) FY2023 Q3 YTD vs. PRIOR YEAR (Actual % change) vs. PRIOR YEAR (CER % change(d)) Revenue 3,212.9 +4.6% 3,212.9 +4.6% +0.0% Operating Profit 224.1 -44.2% 865.6 -9.3% -12.7% Margin 7.0% -6.1pp 26.9% -4.1pp Net Profit 147.1 -48.6% 643.6 -9.0% -12.2% EPS (yen) 94 -48.9% 412 -9.7% -12.9% Operating Cash Flow 437.8 -36.0% Free Cash Flow (Non-IFRS)(a)(b) 36.3 -93.8% (a) Further information regarding certain of Takeda’s Non-IFRS measures is posted on Takeda’s investor relations website at . (b) We define Free Cash Flow as cash flows from operating activities, subtracting acquisition of property, plant and equipment (“PP&E”), intangible assets and investments as well as removing any other cash that is not available to Takeda’s immediate or general business use, and adding proceeds from sales of PP&E, as well as from sales of investments and businesses, net of cash and cash equivalents divested. (c) Core results adjust our reported results calculated and presented pursuant to IFRS to exclude the effect of items unrelated to Takeda’s core operations, such as, to the extent applicable for each line item, non-recurring items, purchase accounting effects and transaction related costs, as well as amortization and impairment of intangible assets and other operating income and expenses. (d) CER (Constant Exchange Rate) change eliminates the effect of foreign exchange rates from year-over-year comparisons by translating Reported or Core results for the current period using corresponding exchange rates in the same period of the previous fiscal year. FY2023 OUTLOOK On track towards full-year FY2023 Management Guidance (Billion yen except per share amounts) FY2023 FORECAST (Unchanged from October 2023) FY2023 MANAGEMENT GUIDANCE Core Change at CER (Non-IFRS) (Unchanged from May 2023) Revenue 3,980.0 Core Revenue 3,980.0 Low-single-digit % decline Reported Operating Profit 225.0 Core Operating Profit 1,015.0 Low-10s % decline Reported Net Profit 93.0 Reported EPS (yen) 59 Core EPS (yen) 447 Low-20s % decline Free Cash Flow* 400.0-500.0 Annual Dividend per Share (yen) 188 *Free Cash Flow forecast reflects expenditures related to the acquisition of TAK-279 from Nimbus and in-licensing of FRUZAQLA (fruquintinib) from HUTCHMED. Additional Information About Takeda’s FY2023 Q3 Earnings Results For more details on Takeda’s FY2023 Q3 results and other financial information, including key assumptions in FY2023 forecast and management guidance, please visit: For more information on Takeda’s commercial progress across the five key business areas and pipeline updates, please visit: About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit . 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 press 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. The product names appearing in this document are trademarks or registered trademarks owned by Takeda, or their respective owners. 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); the extent to which our internal energy conservation measures and future advancements in renewable energy or low carbon energy technology will enable us to reduce our greenhouse gas emissions; 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: or at . Takeda does not undertake to update any of the forward-looking statements contained in this report 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 report may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results. Financial information and Certain Non-IFRS Financial Measures Takeda’s financial statements are prepared in accordance with International Financial Reporting Standards (“IFRS”). This press release and materials distributed in connection with this press release include certain financial measures not presented in accordance with IFRS, such as Core Revenue, Core Operating Profit, Core Net Profit, Core EPS, Constant Exchange Rate (“CER”) change, Net Debt, EBITDA, Adjusted EBITDA and Free Cash Flow. Takeda’s management evaluates results and makes operating and investment decisions using both IFRS and non-IFRS measures included in this presentation. These non-IFRS measures exclude certain income, cost and cash flow items which are included in, or are calculated differently from, the most closely comparable measures presented in accordance with IFRS. By including these non-IFRS measures, management intends to provide investors with additional information to further analyze Takeda’s performance and core results, including when controlling for the effect of fluctuations in exchange rates. Takeda’s non-IFRS measures are not prepared in accordance with IFRS and such non-IFRS measures should be considered a supplement to, and not a substitute for, measures prepared in accordance with IFRS (which we sometimes refer to as “reported” measures). Investors are encouraged to review the definitions and reconciliations of non-IFRS financial measures to their most directly comparable IFRS measures, which are in the financial appendix at the end of Takeda's FY2023 Q3 investor presentation (available at takeda.com/investors/financial-results/quarterly-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. Please refer to slide 17 of Takeda’s FY2023 Q3 investor presentation (available at takeda.com/investors/financial-results/quarterly-results/) for the definition of Growth & Launch Products. View source version on businesswire.com: Contacts Investor Relations Christopher O’Reilly Christopher.oreilly@takeda.com +81 (0) 3-3278-2543 Media Relations Brendan Jennings Brendan.jennings@takeda.com +81 (0) 3-3278-2111 Source: Takeda Pharmaceutical Company Limited View this news release online at:

Drug ApprovalFinancial StatementVaccine

21 Dec 2023

·www.biospace.com

Takeda Announces China NMPA Approval of LIVTENCITY® (maribavir) for the Treatment of Adults With Post-transplant Cytomegalovirus (CMV) Refractory to Prior Therapies

- LIVTENCITY Is the First and Only Inhibitor of CMV-specific UL97 Protein Kinase Approved in China for the Treatment of Adults With Post-transplant CMV Infection/Disease Refractory* to Conventional Anti-CMV Treatment - Approval Based on Phase 3 TAK-620-303 SOLSTICE Study Demonstrating Maribavir Was Superior to Conventional Therapies at Week 8, for Primary Endpoint1 - CMV Is One of the Most Common and Serious Post-transplant Infections and Can Lead to Other Serious Infections, Loss of Transplanted Organ and Failure of Graft2,3 OSAKA, Japan & CAMBRIDGE, Massachusetts--(BUSINESS WIRE)-- Takeda (TSE:4502/NYSE:TAK) today announced that LIVTENCITY® (maribavir) has been approved by the National Medical Products Administration (NMPA) of China for the treatment of adult patients with post-hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT) cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir or foscarnet. LIVTENCITY is the first and only inhibitor of CMV-specific UL97 protein kinase in China for this indication. LIVTENCITY was granted Breakthrough Therapy Designation by China Center for Drug Evaluation (CDE) in 2021. “The approval of LIVTENCITY by the NMPA of China recognizes the critical need for post-transplant care and that CMV infection, when not successfully treated, can pose serious challenges to transplant recipients that can lead to complications such as increased organ rejection and hospitalization rates,” said Ramona Sequeira, president, Global Portfolio Division, Takeda. “This approval will help redefine the CMV treatment landscape for transplant patients in China and is a positive step forward toward addressing an unmet need for this community.” The NMPA approval is based on the results of the Phase 3 SOLSTICE trial, which evaluated the safety and efficacy of maribavir versus conventional antiviral therapies – ganciclovir, valganciclovir, cidofovir or foscarnet – for the treatment of patients with CMV infection/disease refractory* to prior therapies. In the SOLSTICE trial, LIVTENCITY was superior to conventional therapies at Week 8 for the primary endpoint of confirmed CMV viremia clearancea in post-transplant adults with refractory* CMV infection.1 The NMPA approval marks the 12th approval of LIVTENCITY around the world for post-transplant CMV refractory* to prior therapies, including four other major markets beyond China: the United States, Canada, Australia and the European Union.4-7 Out of the estimated 200,000 adult transplants per year globally, CMV is one of the most common infections experienced by transplant patients with an estimated incidence rate of 16%-56% in SOT and 30%-80% in HSCT recipients.8,9 About LIVTENCITY LIVTENCITY (maribavir), an orally bioavailable anti-CMV compound, is the first and only antiviral agent that targets and inhibits the UL97 protein kinase and thus its natural substrates.1 It is approved by the National Medical Products Administration (NMPA) of China for the treatment of adults with post-HSCT or SOT cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir or foscarnet. Product Name LIVTENCITY 200 mg film coated tablets. Generic Name Maribavir Posology and Administration LIVTENCITY should be initiated by a physician experienced in the management of patients who have undergone solid organ transplant or hematopoietic stem cell transplant. Posology: The recommended dose of LIVTENCITY is 400 mg (two 200 mg tablets) twice daily resulting in a daily dose of 800 mg for 8 weeks. Treatment duration may need to be individualized based on the clinical characteristics of each patient. Pediatric population: The safety and efficacy of LIVTENCITY in patients below 18 years of age have not been established. No data are available. Method of administration: Oral use. LIVTENCITY is intended for oral use only and can be taken with or without food. The film coated tablet can be taken as a whole tablet, a crushed tablet, or a crushed tablet through a nasogastric or orogastric tube. 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* 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.1 The trial’s primary efficacy endpoint was confirmed CMV viremia clearance a at the end of Week 8. The key secondary endpoint was confirmed CMV viremia clearance and CMV infection symptom control† at the end of Study Week 8 with maintenance of this treatment effect through Study Week 16.1 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.10 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.8 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 30-80% in HSCT recipients.8,9 In transplant recipients, reactivation of CMV can lead to serious consequences including graft loss and, in extreme cases, can be fatal.1,2 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.11 Additionally, existing therapies may require or prolong hospitalization due to administration.11,12 About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit . LIVTENCITY Safety Information Contraindications Hypersensitivity to the active substance or to any of the excipients and co-administration with ganciclovir or valganciclovir. Special warnings and precautions for use Virologic failure can occur during and after treatment with LIVTENCITY. Some maribavir pUL97 resistance-associated substitutions confer cross-resistance to ganciclovir and valganciclovir. CMV DNA levels should be monitored, and resistance mutations should be investigated in patients who do not respond to treatment. Treatment should be discontinued if maribavir resistance mutations are detected. LIVTENCITY is not expected to be effective in treating CMV CNS infections (e.g. meningo encephalitis). LIVTENCITY has the potential to increase the concentrations of immunosuppressants that are cytochrome P450 (CYP)3A/P-gp substrates with narrow therapeutic margins (including tacrolimus, cyclosporine, sirolimus and everolimus). The plasma levels of these immunosuppressants must be frequently monitored throughout treatment with LIVTENCITY, especially following initiation and after discontinuation of LIVTENCITY, and doses should be adjusted, as needed. The concomitant use of LIVTENCITY and certain medicinal products may result in known or potentially significant medicinal product interactions, some of which may lead to: possible clinically significant adverse reactions from greater exposure of concomitant medicinal products. reduced therapeutic effect of LIVTENCITY. Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’. Pregnancy & Breast-feeding: LIVTENCITY is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast feeding should be discontinued during treatment with LIVTENCITY. Interactions If dose adjustments of concomitant medicinal products are made due to treatment with maribavir, doses should be readjusted after treatment with maribavir is completed. Effect of other medicinal products on maribavir: Co-administration of maribavir with strong cytochrome P450 3A (CYP3A) inducers rifampicin, rifabutin or St. John’s wort is not recommended. If co-administration of maribavir with other strong or moderate CYP3A inducers (e.g., carbamazepine, efavirenz, phenobarbital and phenytoin) cannot be avoided, the maribavir dose should be increased to 1 200 mg twice daily. No dose adjustment is needed when maribavir is co-administrated with CYP3A inhibitors. Effect of maribavir on other medicinal products: Co-administration of maribavir with valganciclovir and ganciclovir is contraindicated. Concomitant administration of maribavir and medicinal products that are sensitive substrates of CYP1A2 with a narrow therapeutic window (e.g., tizanidine and theophylline) should be avoided due to the risk for lack of efficacy of CYP1A2 substrates. When the immunosuppressants tacrolimus, cyclosporine, everolimus or sirolimus are co-administered with maribavir, immunosuppressant levels should be frequently monitored throughout treatment with maribavir, especially following initiation and after discontinuation of maribavir and dose adjusted, when needed. Caution should be exercised when maribavir and sensitive P-gp substrates (e.g., digoxin, dabigatran) are co administered. Serum digoxin concentrations should be monitored, and dose of digoxin may need to be reduced, as needed. Co-administration of maribavir with sensitive BCRP substrates such as rosuvastatin, is expected to increase their exposure and lead to undesirable effects. Adverse Reactions Very common (≥1/10) Taste disturbance, Diarrhea, Nausea, Vomiting, Fatigue Common (≥1/100 to <1/10) Headache, Abdominal pain upper, Decreased appetite, Immunosuppressant drug level increased, Weight decreased The most commonly reported serious adverse reactions were diarrhea (2%) and nausea, weight decreased, fatigue, immunosuppressant drug concentration level increased, and vomiting (all occurring at >1%). Please consult the LIVTENCITY (maribavir) approved label before prescribing, particularly in relation to dosing and treatment monitoring. For the European Union, please consult the Summary of Products Characteristics (SmPC). For China, please consult the LIVTENCITY China Package Leaflet. For full U.S. Prescribing Information, including the approved indication and important safety information, please visit: 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: or at . 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. * Including a subgroup with genotypic resistance to conventional therapies. a Defined as confirmed CMV DNA concentration below the lower limit of quantification (<LLOQ; i.e., <137 IU/mL) in two consecutive samples separated by at least five days. † 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. References Avery R, Alain S, Alexander BD, et al. SOLSTICE Trial Investigators. Maribavir for refractory cytomegalovirus infections with or without resistance post-transplant: results from a phase 3 randomized clinical trial. Clin Infect Dis. 2022;75(4):690–701. doi:10.1093/cid/ciab988 Ramanan P, Razonable RR. Cytomegalovirus infections in solid organ transplantation: a review. Infection & Chemotherapy. 2013;45(3):260 Camargo JF, Komanduri KV. Emerging concepts in cytomegalovirus infection following hematopoietic stem cell transplantation. Hematol Oncol Stem Cell Ther. 2017;10(4):233-238. doi:10.1016/j.hemonc.2017.05.001 Takeda. Health Canada approves Takeda’s LIVTENCITYTM (maribavir) the first and only treatment for adults with post-transplant cytomegalovirus (CMV) infection. Published September 20, 2022. Accessed December 12, 2023. Takeda. Takeda’s LIVTENCITY (maribavir) approved by U.S. FDA as the first and only treatment for people ages 12 and older with post-transplant cytomegalovirus (CMV), refractory (with or without genotypic resistance) to conventional antiviral therapies. Published November 23, 2021. Accessed December 12, 2023. Therapeutic Goods Administration (TGA). LIVTENCITY maribavir 200 mg film coated tablet bottle (380132) [Australian product information]. Therapeutic Goods Administration (TGA). Published October 8, 2022. Takeda. European Commission (EC) approves LIVTENCITY (maribavir) for the treatment of adults with post-transplant cytomegalovirus (CMV) infection and/or disease that are refractory (with or without resistance) to one or more prior therapies. Published November 11, 2022. Accessed December 12, 2023. Azevedo LS, Pierrotti LC, Abdala E, et al. Cytomegalovirus infection in transplant recipients. Clinics (Sao Paolo). 2015;70(7):515-523. doi:10.6061/clinics/2015(07)09 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. doi:10.1007/s40121-017-0180-z de la Hoz RE, Stephanie G, Sherlock C. Diagnosis and treatment approaches to CMV infections in adult patients. J Clin Virol. 2002;25(Suppl 1):S1-S12. doi:10.1016/s1386-6532(02)00091-4 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 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):500-6. doi:10.1016/j.jinf.2014.07.001

Clinical ResultPhase 3Drug ApprovalBreakthrough TherapyPriority Review

100 Deals associated with Maribavir

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D04859	Maribavir	J05AX10	DB06234

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Indication	Country/Location	Organization	Date
Cytomegalovirus Infections	US	Takeda Pharmaceuticals U.S.A., Inc.	23 Nov 2021

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 1	US	Glaxo Wellcome SA	31 Aug 2001

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EHA2024	Not Applicable	Peripheral Stem Cell Transplantation	12	Maribavir 400 mg twice daily	evjmdganjg(ntsibwesbv) = bihdcamauv tgyvszflib (isaggkvxqr, 100 - 1864500)	Positive	14 May 2024
NCT05382104 (CTgov)	Phase 1	-	31	Maribavir (Treatment A: Maribavir 400 mg)	ikiqflrkhy(ntrkxpnkna) = kffhzdjmst wygmhhhlmq (koacmqoatr, idnoapsztm - xhqkyhuemm) View more	-	16 Feb 2024
				Maribavir (Treatment B: Maribavir 400 mg)	ikiqflrkhy(ntrkxpnkna) = xyohqkjugk wygmhhhlmq (koacmqoatr, stdxbvdnoz - todbpomhwa) View more
NCT02927067 (AURORA, Pubmed)	Phase 3	Cytomegalovirus Infections	-	Valganciclovir (dose-adjusted for renal clearance)	nyhksivytw(qprfsofxyg) = rmobzqcrlf srmhgottmp (ibsrtmdose ) View more	Negative	30 Nov 2023
NCT02931539 (SOLSTICE, Pubmed)	Phase 3	Cytomegalovirus Infections	352	Maribavir	yvblvsqoqo(zfgqyfprtl) = zdkjpelyrp qepwgqafwf (izesasumvb )	-	28 Jul 2023
				Investigator-assigned standard therapy (IAT)	yvblvsqoqo(zfgqyfprtl) = euvtymxstg qepwgqafwf (izesasumvb )
NCT02931539 (SOLSTICE, EBMT2023)	Phase 3	Cytomegalovirus Infections	234	Maribavir	pxljzaygks(fmsjmdcysv) = rlormdtlmj uzihaxvghx (ehpoqmsjdc )	-	23 Apr 2023
NCT02927067 (AURORA, CTgov)	Phase 3	Cytomegalovirus Infections	553	Placebo+valganciclovir (Valganciclovir 900 mg BID)	wwqcwyfpkc(qnlqywiybt) = grlpjxqwqa eosfychlsc (ztgpwjvoxc, fegkfyxtcl - ywqkpgcbla) View more	-	03 Mar 2023
				Placebo+Maribavir (Maribavir 400 mg BID)	wwqcwyfpkc(qnlqywiybt) = ifwebufuik eosfychlsc (ztgpwjvoxc, xbhzvlxyon - sohadaveqc) View more
NCT04497883 (CTgov)	Phase 1	-	24	Maribavir (200 mg)	mredawjrdw(ivzrgbxspm) = svkdgeinwd zewpaffhxp (dxeqzdyvuj, cmpdujuvsx - puketmmjmd) View more	-	08 Feb 2022
NCT02931539 (Pubmed) Manual	Phase 3	Cytomegalovirus Infections	352	Maribavir	tejjjmayxh(bgflrmmbbj) = qybgbvmjzg onpcwelecq (cfowcnlizw ) View more	Superior	02 Dec 2021
				IAT	tejjjmayxh(bgflrmmbbj) = mshlmxcvtx onpcwelecq (cfowcnlizw ) View more
NCT02931539 (Phase 3 Study of Maribavir, ASN2021)	Phase 3	Cytomegalovirus Infections	-	Maribavir (MBV)	emvjkdxvpu(bodttthwow) = jsaiiondoh atjsydivbk (azotgvpncv ) View more	Positive	27 Oct 2021
				Investigator-Assigned Therapy (IAT)	emvjkdxvpu(bodttthwow) = iaygrwflkc atjsydivbk (azotgvpncv ) View more
NCT02931539 (Phase 3 Study of Maribavir \| SOLSTICE, CTgov)	Phase 3	Cytomegalovirus Infections	352	ganciclovir+cidofovir+foscarnet+valganciclovir (Investigator-assigned Anti-CMV Treatment (IAT))	ghovmrbzgp(pxbslvxggz) = ghnayweclz stqhywelfe (krzpipqgvp, gcvhujousx - buhswwzhxq) View more	-	23 Sep 2021
				Maribavir (Maribavir 400 mg)	ghovmrbzgp(pxbslvxggz) = isafhxzqin stqhywelfe (krzpipqgvp, mablkkjijs - gjybdkrwoc) View more

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Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis