Foscarnet Sodium

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. 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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:

The Company’s leading R&D capabilities and robust, expanded manufacturing capacity are helping to address chronic market shortages BRIDGEWATER, N.J.--(BUSINESS WIRE)-- Amneal Pharmaceuticals, Inc. (Nasdaq: AMRX) (“Amneal” or the “Company”) today announced the continued expansion of its injectables portfolio with six new injectable product launches during the second quarter of 2024, bringing the Company’s total number of commercial injectable products available for the U.S. institutional market to over 40. The growth of Amneal’s broad injectables portfolio will help address shortages of critical products where there may be little or no clinical alternative, including in key categories such as oncology. The American Society of Health System Pharmacists (ASHP) currently lists 323 active U.S. drug shortages, with about half representing injectables. Notably, three of Amneal’s six new injectable products are currently on the ASHP drug shortage list. With these new launches, Amneal now provides 13 injectables that are on the ASHP shortage list. Amneal’s Q2 2024 injectable product launches: Product launch Dosage form ASHP drug shortage 1 PEMRYDI RTU® Vial No 2 Atropine sulfate Prefilled syringe Yes 3 Docetaxel Injection Yes 4 Foscarnet IV bag No 5 Methylprednisolone acetate Multi-dose vial Yes 6 Calcium gluconate Vial No “The persistent shortage of quality injectables is driven by multiple factors, including unstable market economics, supply chain disruptions and the need for supply redundancy. Amneal has made meaningful investments to expand our capacity and capabilities and deliver on our goal to be a significant injectables player. Importantly, we are building a robust portfolio of injectables that can serve as a reliable solution to market shortages. We are focused on being a partner our customers can count on to provide a consistent supply of high-quality medicines for their patients,” said Andy Boyer, Executive Vice President, Chief Commercial Officer – Generics. Amneal has tripled its injectables capacity to 60 million units across four manufacturing facilities over the past few years and expects to have over 60 commercial injectable products in 2025. In particular, the Company is launching branded oncology 505(b)(2) products such as PEMRYDI RTU®. These injectables are new, ready-to-use presentations that can improve pharmacy efficiency by reducing clinician steps. Amneal expects to launch two to three new 505(b)(2) injectables per year going forward. About Amneal Amneal Pharmaceuticals, Inc. (Nasdaq: AMRX), headquartered in Bridgewater, NJ, is a global pharmaceuticals company. We make healthy possible through the development, manufacturing, and distribution of a diverse portfolio of over 280 pharmaceutical products, primarily within the United States. In its Generics segment, the Company is expanding across a broad range of complex product categories and therapeutic areas, including injectables and biosimilars. In its Specialty segment, Amneal has a growing portfolio of branded pharmaceuticals focused primarily on central nervous system and endocrine disorders, with a pipeline focused on unmet needs. Through its AvKARE segment, the Company is a distributor of pharmaceuticals and other products for the U.S. federal government, retail, and institutional markets. For more information, please visit . Cautionary Statement on Forward-Looking Statements Certain statements contained herein, regarding matters that are not historical facts, may be forward-looking statements (as defined in the U.S. Private Securities Litigation Reform Act of 1995). Such forward-looking statements include statements regarding management’s intentions, plans, beliefs, expectations, financial results, or forecasts for the future, including among other things: discussions of future operations; expected or estimated operating results and financial performance; and statements regarding our positioning, including our ability to drive sustainable long-term growth, and other non-historical statements. Words such as “plans,” “expects,” “will,” “anticipates,” “estimates,” and similar words, or the negatives thereof, are intended to identify estimates and forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These forward-looking statements are based on current expectations of future events, including with respect to future market conditions, company performance and financial results, operational investments, business prospects, new strategies and growth initiatives, the competitive environment, and other events. If the underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of the Company. Such risks and uncertainties include, but are not limited to: our ability to successfully develop, license, acquire and commercialize new products on a timely basis; the competition we face in the pharmaceutical industry from brand and generic drug product companies, and the impact of that competition on our ability to set prices; our ability to obtain exclusive marketing rights for our products; our revenues are derived from the sales of a limited number of products, a substantial portion of which are through a limited number of customers; the impact of a prolonged business interruption within our supply chain; the continuing trend of consolidation of certain customer groups; our dependence on third-party suppliers and distributors for raw materials for our products and certain finished goods; legal, regulatory and legislative efforts by our brand competitors to deter competition from our generic alternatives; our dependence on information technology systems and infrastructure and the potential for cybersecurity incidents; our ability to attract, hire and retain highly skilled personnel; risks related to federal regulation of arrangements between manufacturers of branded and generic products; our reliance on certain licenses to proprietary technologies from time to time; the significant amount of resources we expend on research and development; the risk of claims brought against us by third parties; risks related to changes in the regulatory environment, including U.S. federal and state laws related to healthcare fraud abuse and health information privacy and security and changes in such laws; changes to Food and Drug Administration product approval requirements; the impact of healthcare reform and changes in coverage and reimbursement levels by governmental authorities and other third-party payers; our dependence on third-party agreements for a portion of our product offerings; our substantial amount of indebtedness and our ability to generate sufficient cash to service our indebtedness in the future, and the impact of interest rate fluctuations on such indebtedness; our potential expansion into additional international markets subjecting us to increased regulatory, economic, social and political uncertainties; our ability to identify, make and integrate acquisitions or investments in complementary businesses and products on advantageous terms; the impact of global economic, political or other catastrophic events; our obligations under a tax receivable agreement may be significant; and the high concentration of ownership of our Class A common stock and the fact that we are controlled by the Amneal Group. The forward-looking statements contained herein are also subject generally to other risks and uncertainties that are described from time to time in the Company’s filings with the Securities and Exchange Commission, including under Item 1A, “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and in its subsequent reports on Forms 10-Q and 8-K. Investors are cautioned not to place undue reliance on any such forward-looking statements, which speak only as of the date they are made. Forward-looking statements included herein speak only as of the date hereof and we undertake no obligation to revise or update such statements to reflect the occurrence of events or circumstances after the date hereof. View source version on businesswire.com: Contacts Contact Anthony DiMeo VP, Investor Relations & Media anthony.dimeo@amneal.com Source: Amneal Pharmaceuticals, Inc. View this news release online at: