Colistimethate Sodium

EMBLAVEOTM is the first and only monobactam/β-lactamase inhibitor combination antibiotic therapy approved by the U.S. FDA to treat complicated intra-abdominal infections, including those caused by Gram-negative bacteria Gram-negative bacterial infections represent a significant public health threat due to their ability to develop resistance to antimicrobial therapies Antimicrobial resistance (AMR) could lead to over 39 million deaths worldwide by 2050, and new treatments are urgently needed1 NORTH CHICAGO, Ill., Feb. 7, 2025 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the U.S. Food and Drug Administration (FDA) has approved EMBLAVEO™ (aztreonam and avibactam), as the first and only fixed-dose, intravenous, monobactam/β-lactamase inhibitor combination antibiotic. It is approved in combination with metronidazole, for patients 18 years and older who have limited or no alternative options for the treatment of complicated intra-abdominal infections (cIAI), including those caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens. Approval of this indication is based on limited clinical safety and efficacy data for EMBLAVEO. Gram-negative bacterial infections are among the most challenging for healthcare professionals to control due to high antimicrobial resistance (AMR).2 When AMR develops, medicines intended to treat these infections become ineffective, increasing the risk of morbidity and mortality.2 "The continued evolution of antimicrobial resistance among Gram-negative bacteria has left some patients with little to no treatment options, resulting in extended hospital stays, additional morbidity and death," said James A. McKinnell, M.D., infectious disease specialist, Milefchik-Rand Medical Group, Torrance Memorial Medical Center in Torrance, California. "The approval of EMBLAVEO provides physicians a much-needed therapeutic option to help address some of the most difficult antimicrobial-resistant pathogens and provides doctors an opportunity to treat patients with these challenging infections." AMR is considered an urgent global public health threat and could lead to over 39 million deaths worldwide by 2050.1 An estimated 1.14 million deaths globally were attributed to bacterial AMR in 2021 alone.1 If AMR remains unaddressed, minor infections and routine surgical procedures could become life-threatening or fatal.2 The FDA has prioritized the research and development of new medicines to treat AMR and help prevent the spread of infection.3 "As bacteria evolve, industry, government, and clinical experts must work together to ensure that the infectious disease community has the tools to advance public health," said Roopal Thakkar, M.D., executive vice president, research & development, chief scientific officer, AbbVie. "We're proud to offer this important novel treatment option to urgently address the significant threat of antimicrobial resistance." EMBLAVEO is a medication that combines two components: aztreonam, a monobactam antibiotic, and avibactam, a β-lactamase inhibitor that protects aztreonam from serine β-lactamase hydrolysis and restores its activity against bacteria that co-produce Metallo-β-lactamases (MBLs) and serine β-lactamases.4 MBLs are a type of enzyme produced by certain bacteria that can become resistant to antibiotics and are on the rise globally.5 The approval of EMBLAVEO was supported by prior findings regarding the efficacy and safety of aztreonam for the treatment of cIAI.6 It was also supported by clinical trial results from the Phase 3 REVISIT study, which evaluated the efficacy, safety, and tolerability of EMBLAVEO for the treatment of serious infections due to Gram-negative bacteria, including MBL-producing multidrug-resistant pathogens, for which there are limited or no treatment options.7 In 2019, the FDA granted Qualified Infectious Disease Product (QIDP) Designation and Fast Track Designation for EMBLAVEO.8 The QIDP Designation provides certain incentives for the development of new antibiotics, including priority review and eligibility for the FDA's Fast Track Designation, and a five-year regulatory exclusivity extension.8 The Fast Track Designation is designed to facilitate the development of and accelerate the review of drugs to treat serious conditions that do not have sufficient treatment options.8 EMBLAVEO will be available for commercial use in the U.S. in Q3 2025. About the Phase 3 REVISIT Study7 The Phase 3 REVISIT clinical trial is a randomized, active-controlled, central assessor-blinded, multicenter trial evaluating EMBLAVEO ± metronidazole versus the combination of meropenem ± colistin in patients with cIAI or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (not an approved indication for EMBLAVEO). The study enrolled 422 patients across 81 locations globally. The primary endpoint was clinical cure at the test-of-cure visit in the intent-to-treat (ITT) population. Secondary endpoints included 28-day mortality in the ITT population, and safety in patients in the ITT population who received the study drug. The REVISIT trial included 312 hospitalized patients with cIAI that were randomized 2:1 to receive treatment with EMBLAVEO with metronidazole or meropenem ± colistin for five to 14 days of therapy. The trial was not designed with any formal hypotheses for inferential testing against the active comparator. More information on the study can be found on (NCT03329092) and in The Lancet Infectious Disease. About EMBLAVEO™ EMBLAVEO ™ is indicated in patients 18 years and older who have limited or no alternative options for the treatment of complicated intra-abdominal infections (cIAI), including those caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens. Approval of this indication is based on limited clinical safety and efficacy data for EMBLAVEO. It combines aztreonam, a monobactam β-lactam, with avibactam, a broad-spectrum β-lactamase inhibitor.4 Metallo-β-lactamases (MBLs) are a class of β-lactamase enzymes that are not inhibited by current β-lactamase inhibitors and hydrolyze nearly all β-lactam antibiotics, with an exception being monobactams such as aztreonam.4,5 However, monobactams are degraded by other β-lactamases that are frequently co-produced with MBLs, limiting the clinical usefulness of aztreonam monotherapy.4,5 The combination of aztreonam with avibactam restores aztreonam's activity against bacteria that co-produce MBLs and other β-lactamases and provides a well-tolerated and effective treatment option against multidrug-resistant Gram-negative bacteria.4,7 These multidrug-resistant Gram-negative bacteria include carbapenem-resistant Enterobacterales (CRE) and S. maltophilia.4,5 CRE, including those that produce MBLs, have been highlighted as an urgent threat by the U.S. Centers for Disease Control and Prevention.9 In April 2024, the European Commission granted marketing authorization for EMBLAVEO® for the treatment of adult patients with cIAI, hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), and complicated urinary tract infections (cUTI), including pyelonephritis.10 It is also indicated for the treatment of infections due to aerobic Gram-negative organisms in adult patients with limited treatment options.10 The marketing authorization for EMBLAVEO was approved in Great Britain in June 2024, and other global submissions are ongoing. EMBLAVEO was jointly developed with Pfizer. AbbVie holds the rights to commercialize the therapy in the U.S. and Canada, with Pfizer responsible for commercialization in all other areas. Development of EMBLAVEO was also supported by public-private partnerships with the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA) under OTA number HHSO100201500029C; and through the EU's Innovative Medicines Initiative (IMI) – a partnership between the EU and the European pharmaceutical industry – under a project called Combatting Bacterial Resistance in Europe – Carbapenem Resistance (COMBACTE-CARE), grant agreement No. 115620. The COMBACTE-CARE consortium is a unique public-private collaboration that unites the knowledge and capabilities of leading drug-resistant bacterial infection experts and is supported by the COMBACTE pan-European clinical and laboratory networks. IMPORTANT SAFETY INFORMATION INDICATIONS AND USAGE Complicated Intra-abdominal Infections EMBLAVEO, in combination with metronidazole, is indicated in patients 18 years and older who have limited or no alternative treatment options for the treatment of complicated intra-abdominal infections (cIAI) including those caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens. Approval of this indication is based on limited clinical safety and efficacy data for EMBLAVEO. Usage to Reduce Development of Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of EMBLAVEO and other antibacterial drugs, EMBLAVEO should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. CONTRAINDICATIONS EMBLAVEO is contraindicated in patients with known hypersensitivity to the components of EMBLAVEO (aztreonam and avibactam). WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions were noted in patients treated with EMBLAVEO, including rash, flushing, and bronchospasm. Prior to treatment, it should be established if the patient has a history of hypersensitivity reactions to components of EMBLAVEO (aztreonam and avibactam). In case of hypersensitivity reactions, immediately discontinue EMBLAVEO and initiate appropriate medications and/or supportive care. Serious Skin Disorders Cases of toxic epidermal necrolysis have been reported in association with aztreonam (a component of EMBLAVEO) in patients undergoing bone marrow transplant with multiple risk factors including sepsis, radiation therapy, and other concomitantly administered drugs associated with toxic epidermal necrolysis. Discontinue EMBLAVEO if a serious skin reaction occurs. Hepatic Adverse Reactions Elevations in hepatic transaminases have been observed during treatment with EMBLAVEO. Monitoring of liver-related laboratory tests is recommended while on treatment, particularly in patients with baseline liver comorbidities or on concomitant hepatotoxic medications. If transaminase elevations are noted, consider discontinuing EMBLAVEO, if clinically indicated, and monitor the patient for resolution of any pertinent clinical and laboratory findings. Clostridioides Difficile -Associated Diarrhea Clostridioides difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs, including EMBLAVEO, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial drugs alters the normal flora of the colon and may permit overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial drugs. If CDAD is suspected or confirmed, antibacterial drugs not directed against C. difficile may need to be discontinued. Manage fluid and electrolyte levels as appropriate, supplement protein intake, monitor antibacterial treatment of C. difficile, and institute surgical evaluation as clinically indicated. Development of Drug-Resistant Bacteria Prescribing EMBLAVEO in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. ADVERSE REACTIONS The most common adverse reactions occurring at an incidence of greater than 5% were hepatic adverse reactions, anemia, diarrhea, hypokalemia, and pyrexia. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. Please click here for Full Prescribing Information. Globally, prescribing information varies; refer to the individual country product label for complete information. About AbbVie AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at . Follow @AbbVie on X (formerly Twitter), Facebook, Instagram, YouTube, and LinkedIn. Forward-Looking Statements  Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2023 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.  Contact(s): U.S. Media: Alyssa Rege [email protected] Investors: Liz Shea [email protected] References 1 Naghavi, Mohsen, et al. "Global burden of bacterial antimicrobial resistance 1990–2021: A systematic analysis with forecasts to 2050." The Lancet, vol. 404, no. 10459, 16 Sept. 2024, pp. 1199–1226. 2 World Health Organization. Antimicrobial resistance. November 2023. Available at: . Last accessed January 2025. 3 The U.S. Food and Drug Administration. Antimicrobial Resistance. Available at: . Last accessed January 2025. 4 Rossolini GM, Stone G, Kantecki M, et al. In vitro activity of aztreonam/avibactam against isolates of Enterobacterales collected globally from ATLAS in 2019. J Glob Antimicrob Resist. 2022;30:214–221. 5 Boyd SE, Livermore DM, Hooper DC, et al. Metallo-β-lactamases: Structure, function, epidemiology, treatment options, and the development pipeline. Antimicrob Agents Chemother. 2020;64(10):e00397-20. 6 AZACTAM®, Package Insert. Bristol Myers Squibb, 2018. 7 Carmeli Y, Cisneros-Herreros JM, Paul M, et al. Aztreonam–avibactam versus meropenem for the treatment of serious infections caused by Gram-negative bacteria (REVISIT): a descriptive, multinational, open-label, phase 3, randomised trial. Lancet Infect Dis 2024:S1473-3099(24)00499-7. 8 AbbVie. Allergan Receives FDA Qualified Infectious Disease Product (QIDP) Designation And Fast Track Designation For ATM-AVI (Aztreonam And Avibactam) For Antibiotic-Resistant Gram-Negative Infections [Press Release]. . 9 Centers for Disease Control and Prevention. Carbapenem-resistant Enterobacterales (CRE): An urgent public health threat. July 2021. Available at: . Last accessed January 2025. 10 Pfizer Inc. European Commission Approves Pfizer's EMBLAVEO® for Patients with Multidrug-Resistant Infections and Limited Treatment Options [Press Release]. . SOURCE AbbVie WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Essential Pharma announces €900 million recapitalisation through a Gyrus Capital Continuation Vehicle led by AlpInvest and new strategic financing from Sixth Street Provides significant resources to build on diversified portfolio of established and rare disease medicines Egham, UK – 12 December 2024 – Essential Pharma (“Essential” or “the Company”), an international specialty pharma group focused on ensuring that patients have access to low volume, clinically differentiated, niche pharmaceutical products across key therapeutic areas, today announces the completion of a €900 million financing, through a Gyrus Capital single-asset Continuation Vehicle led by AlpInvest, a subsidiary of Carlyle Global Investment Solutions, and a new strategic financing facility with Sixth Street. Essential Pharma was acquired in 2019 by Gyrus Capital, who have supported the transformation of the Company into a global, high-growth specialty pharma group with significant development opportunities. The transaction will enable Essential to deploy additional capital to build on its diversified portfolio and late-stage pipeline across established and rare disease medicines. This will be achieved through its successful acquisition and development strategy under the leadership of CEO, Emma Johnson. This additional capital will support Essential’s mission to ensure access to essential medicines for patients across new and existing markets. Since her appointment in 2023, Emma has driven the Company’s expansion into rare diseases, with the addition of marketed product Colobreathe® and Hu14.18, an immunotherapy in late-stage clinical development for the treatment of high-risk neuroblastoma. Following the transaction, Lee Morley, appointed as Non-Executive Director to the Board in 2023, will assume the role of Chairman of Essential Pharma, succeeding Dr Patrick Vink. Lee has more than 30 years’ experience in the biopharmaceutical industry, with extensive knowledge of commercialisation, pricing, reimbursement and product launch strategy. He was a co-founder and CEO at EUSA Pharma before the company’s €750 million acquisition by Recordati (BIT: REC) in 2022. During his time at EUSA Pharma, he led the company’s transition from specialty pharma to oncology and rare disease, driving sales from €20 million to €150 million. Emma Johnson, CEO of Essential Pharma, commented: “This transaction provides us with substantial additional firepower, strengthening our ability to deliver essential medicines to patients who need them most. By moving into new geographical markets and building on our diversified portfolio and late-stage pipeline across our key therapeutic areas, we can expand our reach to help underserved patient populations across the globe. We are excited to continue our relationship with Gyrus Capital as we execute our strategy to become a leading, global specialty pharma group with a growing rare disease presence, where patient needs are often most acute. As we transition to our new ownership, I’d also like to thank Patrick for his significant contributions as Chairman and welcome Lee as he steps into the role.” Dr Robert Watson, Managing Partner at Gyrus Capital, said: “This is a landmark investment for Essential and for Gyrus Capital. We are delighted to partner with AlpInvest, Stepstone, Sixth Street and other significant private capital institutions, who believe in our shared vision of building an exceptional specialty pharma company, and bringing critical medical products to patients across the globe.” Sixth Street, a leading global investment firm with deep experience supporting biotech companies across all stages of growth, is providing a new strategic financing facility consisting of €300 million in structured equity and growth debt. Jeff Pootoolal, Partner at Sixth Street who will join the board of Essential Pharma, said: “Essential Pharma has assembled a leading team and platform in its pursuit of providing patients around the world with critical medicines. We are excited to support Emma and Essential’s leadership as they continue to execute and expand on their mission.” About Essential Pharma Essential Pharma is an international specialty pharmaceutical group dedicated to maintaining access to clinically differentiated, niche, branded medicines across multiple therapeutic areas. The group has been an important and valued partner to healthcare providers for over 20 years by giving underserved patient populations access to medicines that otherwise might not be available, and addressing clinical unmet needs. Essential Pharma operates globally in more than 70 countries, supplying a portfolio of products with a focus on the central nervous system (CNS), gastroenterology, ophthalmology, and rare disease. The group’s growth strategy is centred on portfolio optimisation and a targeted M&A approach to acquire commercial and late-clinical stage assets in the four therapeutic areas of focus. It is a trusted partner to multiple pharma companies of all sizes, with a proven history of integrating assets and managing complex technology transfers seamlessly while ensuring continuous supply to patients. For more information, please visit essentialpharmagroup.com About Gyrus Capital Gyrus Capital is a European investment firm dedicated to transformational investments in the healthcare and sustainability sectors. Based in Geneva, Switzerland, Gyrus invests in businesses that address the structural needs of society and the environment and are positioned for long-term sustainable growth. The firm focuses on complex transactions, particularly corporate carve-outs in the €50 million to €500 million range. A renowned group of experienced partners and industry experts supports Gyrus’s active investment and value-creation approach, working closely with entrepreneurs and managers. To learn more, please visit www.gyruscapital.com About Sixth Street Sixth Street is a global investment firm with over $80 billion in assets under management and committed capital. Sixth Street uses its long-term flexible capital, data-enabled capabilities, and One Team culture to develop themes and offer solutions to companies across all stages of growth. Sixth Street Healthcare and Life Sciences finances the development and commercialization of innovative therapeutics and invests in healthcare technology companies across all stages of growth. Investments in the sector include Apellis Pharmaceuticals, Arrowhead Pharmaceuticals, Arsenal Biosciences, Biohaven, Blueprint Medicines, Caris Life Sciences, Chroma Medicine, ConcertAI, Datavant, Immunogen, Ironwood, and Mammoth Biosciences, among many others. Founded in 2009, Sixth Street has more than 650 team members including over 250 investment professionals operating around the world. For more information, visit www.sixthstreet.com, or follow Sixth Street on LinkedIn. CONTACTS Essential Pharma Emma Johnson, CEO Tel: +44(0)1784 477 167 Email: info@essentialpharmaceuticals.com ICR Healthcare Tracy Cheung/Sukaina Virji/Isabelle Abdou Tel: +44 (0) 20 3709 5700 Email: Essentialpharma@icrhealthcare.com