TOKYO - Tuesday, 03. June 2025
- Celebrating the 50th Anniversary of the announcement of the world's first distributed control system, CENTUM continues to shine in the areas of safety, security, and sustainable autonomous operations -
(BUSINESS WIRE)--Yokogawa Electric Corporation (TOKYO: 6841) announces the unveiling of the next-generation Release 7 concept and the launch of Release 7.01 of the CENTUMTM VP integrated production control system, a core product in the OpreXTM Control and Safety System lineup. This is the 10th generation of the CENTUM series, and its release coincides with the 50th anniversary of the announcement of CENTUM as the world’s first*1 distributed control system (DCS), on June 19, 1975.
Development Background
In addition to the dynamic changes in supply chains over recent years, countries have been strengthening regulations in response to a growing awareness of the need to protect the environment. At the same time, with the increasing use of digital technologies for complex applications such as the management of the utilization of renewable energy and the analysis of data in cloud-based environments, security risks have become a greater concern. Also, while utilizing existing tangible assets, there is a growing need to pass on to others the expertise of seasoned operators, and to reduce the workload and mental burden for personnel who are responsible for systems that must be kept operating around the clock. Amidst the growing complexity of these industry challenges, management and frontline personnel are required to increase competitiveness and strike a balance between the stable manufacturing of superior products and the need to improve efficiency and profitability.
The Concept behind CENTUM VP Release 7
In response to these issues, Yokogawa has based its development of CENTUM VP Release 7 on the concept of enabling autonomous operations*2. With CENTUM, Yokogawa is helping its customers attain sustainability by improving energy efficiency, accelerating decarbonization, and providing a safe and secure working environment. While maintaining the reliability, stability, continuity, robust security, and comprehensive engineering and service network that have been hallmarks of the CENTUM series since its inception, Yokogawa will drive innovations for the future in the following three areas:
Expanded scope of control and monitoring
By securely aggregating a wide range of data scattered throughout the plant, the status of the entire plant can be monitored, and the scope of automated operation can be expanded, enabling safer and more secure operations.
Predictive monitoring through process condition monitoring
By extracting and identifying process-specific events related to operations and predicting deviations from expected values, operators can anticipate changes and take action, helping to achieve more stable operations and improve energy efficiency.
Reduction of operator workload
By presenting future scenarios that leverage operator knowledge and know-how, it supports the operator in making accurate decisions. In addition, autonomous control AI*3 can take over from operators to achieve long-term stable operation. This reduces operator workload and mental stress.
Main Features of Release 7.01
To achieve autonomous operations, it is essential to leverage AI while ensuring safety and security. Release 7.01 helps to establish the necessary foundation for this goal. The key features are as follows.
1. Enhanced security
To achieve data-driven operations, it is crucial to ensure the security of critical infrastructure. This release adopts industry security benchmarks to strengthen the cybersecurity of the components that make up control systems and enhance the overall security level of the system.
2. Expansion of control and monitoring scope with CENTUM
By integrating OPC Unified Architecture (OPC UA) connectivity, the range of plant equipment and devices that can be controlled and monitored by CENTUM is expanded. OPC UA is a platform-independent standard that enables data exchange between devices from different manufacturers in the industrial automation field. In this update, OPC UA client functionality has been added to CENTUM.
3. Enhanced engineering capabilities for large-scale projects
To promote operational optimization by integrating various systems within the plant, a feature has been added that allows the merging and testing of multiple engineering databases related to CENTUM. This enhancement will enable high-quality and efficient engineering, contributing to the rapid startup of new plants and restart of upgraded plants.
Mitsuhiro Yamamoto, Vice President, Executive Officer, and head of the Systems Business Division at Yokogawa Electric stated, “In this VUCA*4 era, the conditions required for manufacturing sites and management are becoming ever more complex. By realizing stable operations and expanding the scope of autonomy, CENTUM VP Release 7 will help our customers achieve a more sustainable society and sustainable business growth.”
*1 CENTUM has been recognized as the world’s first DCS by Japan’s National Museum of Nature and Science, which in 2012 designated CENTUM as such in the document “Important Material for the History of Science and Technology (Heritage of Future Technology)” (Japanese). This status was also confirmed by the Denki no Ishizue (Foundation of Electric Technology) 14th Electric Technology Awards (Japanese).
*2 Yokogawa is advocating the transition from industrial automation to industrial autonomy (IA2IA), and defines industrial autonomy as a state where plant assets and operations possess learning and adaptive capabilities that allow responses with minimal human interaction, empowering operators to perform higher-level optimization tasks. Autonomous operations is the final stage of industrial autonomy, representing an ideal state where operations function with complete autonomy throughout a value chain.
*3 The Factorial Kernel Dynamic Policy Programming (FKDPP) reinforcement learning AI algorithm. Yokogawa defines autonomous control AI as "a robust system capable of deriving optimal control methods and autonomously responding to unexperienced situations to a certain extent." Yokogawa already has experience in integrating the use of an autonomous control AI and CENTUM VP, and this has been officially adopted for use in controlling operations at a chemical plant. For this achievement, which has reduced environmental impact, lessened workloads, and improved safety, Yokogawa has received the Prime Minister's Prize, the highest of the 2023’s Japan Industrial Technology Awards (Nihon Sangyo Gijyutsu Taisho), which was established in 1972.
*4 An acronym that stands for volatility, uncertainty, complexity, and ambiguity
Major Target Markets
Various process industries, including oil and gas, petrochemicals, chemicals, steel, pulp and paper, electric power, and water treatment
Applications
Operation monitoring and automatic control of plants and manufacturing equipment
More Information
CENTUM VP
https://www.yokogawa.com/solutions/products-and-services/control/distributed-control-systems-dcs/centum-vp/
CENTUM 50th Anniversary website
https://www.yokogawa.com/special/centum-50th/index.htm
About CENTUM
CENTUM was announced as the world’s first distributed control system by Yokogawa Electric on June 19, 1975, and is celebrating its 50th anniversary this year. Since its launch, more than 30,000 systems have been deployed in more than 100 countries around the world, supporting a wide range of industries such as oil refining, petrochemicals, specialty chemicals, textiles, steel, pharmaceuticals, food, water, electric power, and gas. It’s development was made possible by Yokogawa’s experience in providing safe and stable control technologies. For over 50 years, CENTUM has continued to evolve as a core plant operations system characterized by reliability, stability, and continuity. By enhancing control functions, it has played a significant role in increasing product functionality, reducing energy consumption, and improving plant productivity. With “trust” as the design theme during development, CENTUM is leading the safe and secure operation of industry, supported by Yokogawa’s global service network.
About OpreX
OpreX is the comprehensive brand for Yokogawa's industrial automation (IA) and control business. The OpreX name stands for excellence in the technologies and solutions that Yokogawa cultivates through the co-creation of value with its customers, and encompasses the entire range of Yokogawa's IA products, services, and solutions. This brand comprises the following five categories: OpreX Transformation, OpreX Control, OpreX Measurement, OpreX Execution, and OpreX Lifecycle. One of the product groups that make up the OpreX Control category is the OpreX Control and Safety System family, which includes CENTUM VP. With its various OpreX Control solutions, Yokogawa is able to quickly effect changes for its customers that lead to a transformation in such areas as management and operations, and provides highly reliable control technology that ensures high efficiency, high quality, and safe and stable plant operations.
With the OpreX brand, Yokogawa will deliver integrated solutions that address specific needs and support its customers in their efforts to transform and grow their businesses.
About Yokogawa
Yokogawa provides advanced solutions in the areas of measurement, control, and information to customers across a broad range of industries, including energy, chemicals, materials, pharmaceuticals, and food. Yokogawa addresses customer issues regarding the optimization of production, assets, and the supply chain with the effective application of digital technologies, enabling the transition to autonomous operations.
Founded in Tokyo in 1915, Yokogawa continues to work toward a sustainable society through its 17,000+ employees in a global network of 128 companies spanning 62 countries.
For more information, visit www.yokogawa.com
The names of corporations, organizations, products, services and logos herein are either registered trademarks or trademarks of Yokogawa Electric Corporation or their respective holders.
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Tuesday, June 3, 2025
SES’s O3b mPOWER System Receives Platinum Space Sustainability Rating
Assessment based on an in-depth analysis of more than 65 parameters across deployment, operations, and end-of-life disposal of the O3b mPOWER mission
(BUSINESS WIRE) -- O3b mPOWER, SES’s second-generation medium earth orbit (MEO) system, has been awarded the Platinum badge by the Space Sustainability Rating (SSR) Association. This is the highest possible SSR rating tier, and has been awarded to the O3b mPOWER constellation of 13 high-throughput and low-latency satellites, eight of which are already in orbit.
The O3b mPOWER mission was assessed across all phases: deployment, operations, and end-of-life disposal. The Platinum rating for O3b mPOWER was based on an in-depth analysis of more than 65 parameters, including: satellite count, orbital region, collision avoidance strategies, adherence to recognised design and operational standards, and SES’s overall approach to data sharing and transparency. SES is the second operator to receive a Platinum rating from the SSR, and the sixth to be officially rated.
Rather than evaluating individual satellites in isolation, the SSR assesses the aggregate sustainability impact of the entire constellation and considers how satellites interact, operate collectively, and contribute to the broader space environment. This recognition indicates that the O3b mPOWER constellation demonstrates minimal impact on the orbital environment beyond what is necessary for mission success and reflects SES’s strong commitment to sustainable space operations and adherence to internationally accepted best practices in space sustainability.
Prof. Jean-Paul Kneib, President of the SSR Association, Academic Director of EPFL Space Center and Head of the Laboratory of Astrophysics (LASTRO), said, "The Space Sustainability Rating provides an independent benchmark to encourage transparency among space actors, promote best practices in space missions, and support the long-term preservation of the orbital environment. The Platinum rating awarded to the O3b mPOWER constellation reflects SES’s strong alignment with the SSR’s criteria across the full mission lifecycle. We celebrate this recognition for the O3b mPOWER constellation and SES’s contribution to a safer, more responsible, and resilient satellite ecosystem. As the SSR continues to evolve, it aims to drive positive change across the space sector by highlighting leadership in space sustainability—such as that demonstrated by SES—and to encourage the global space community to make informed, sustainability-focused decisions."
Milton Torres, Chief Technology Officer of SES, said, “For 40 years, SES has been driving responsible best practices and developing new technologies, partnerships and solutions contributing to sustainable space. This Platinum badge not only highlights our leadership in sustainable space operations but also reinforces our commitment to responsible and innovative practices in the space industry, while supporting long-term space sustainability for all spacecraft operators.”
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About SES
SES has a bold vision to deliver amazing experiences everywhere on Earth by distributing the highest quality video content and providing seamless data connectivity services around the world. As a provider of global content and connectivity solutions, SES owns and operates a geosynchronous earth orbit (GEO) fleet and medium earth orbit (MEO) constellation of satellites, offering a combination of global coverage and high-performance services. By using its intelligent, cloud-enabled network, SES delivers high-quality connectivity solutions anywhere on land, at sea or in the air, and is a trusted partner to telecommunications companies, mobile network operators, governments, connectivity and cloud service providers, broadcasters, video platform operators and content owners around the world. The company is headquartered in Luxembourg and listed on Paris and Luxembourg stock exchanges (Ticker: SESG). Further information is available at: www.ses.com
About the SSR
The Space Sustainability Rating is a voluntary initiative launched by the World Economic Forum in 2016 and developed since 2018 by a consortium of academic and institutional partners including the European Space Agency (ESA), Massachusetts Institute of Technology (MIT), BryceTech, and the University of Texas at Austin. Created in consultation with industry, policy, and academic stakeholders, the SSR encourages responsible behavior in space by evaluating missions against a set of transparent sustainability criteria. The SSR provides a comprehensive framework for assessing the sustainability of space missions, identifying areas for improvement, and offering operators a chance to communicate their sustainability practices through independent, badge-based ratings: Bronze, Silver, Gold, or Platinum. Each SSR rating also includes actionable recommendations to guide operators in enhancing sustainability practices over time. This approach empowers responsible space actors to continuously evolve their mission strategies and set new benchmarks for space stewardship.
For more information visit: https://spacesustainabilityrating.org/
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Contacts
For further information please contact:
Suzanne Ong
Communications
Tel. +352 710 725 500
suzanne.ong@ses.com
Rayane Maalouf
SSR Communications
contact@ssr.space
HCLTech and UiPath Partner to Accelerate Agentic Automation for Global Enterprises
(BUSINESS WIRE) -- HCLTech, a leading global technology company, and UiPath (NYSE: PATH), a global leader in agentic automation, today announced a strategic partnership to accelerate agentic automation for UiPath customers globally. The partnership will drive large-scale transformation for enterprises across industries, enabling more intelligent and self-sufficient business process operations that require minimal human intervention.
HCLTech will leverage its AI expertise to deploy the UiPath Platform™, enabling autonomous operations in finance, supply chain, procurement, customer service, marketing and human resources. HCLTech will support this partnership with pre-configured AI agents and controls to ensure seamless deployment and scalability. The partnership aims to enhance business agility, optimize workforce efficiency and deliver faster returns on business process automation investments for global enterprises.
HCLTech will also establish an AI Lab with UiPath in India to develop Industry Focused Repeatable Solutions (IFRS) and MVPs for the full automation lifecycle, from strategy to implementation and continuous optimization. HCLTech will leverage its global delivery model to support UiPath customers in North America, Europe and Asia-Pacific.
"As we shift towards a new era with Agentic AI, agentic automation will be critical to provide businesses with the speed and agility to transform operations and unlock new business potential. Partnering with HCLTech allows UiPath to extend the power of its AI-powered automation to enterprises globally, accelerating intelligent transformation at scale. With HCLTech's deep expertise in AI, automation and industry solutions, UiPath customers will benefit from best-in-class implementation and business impact," said Ashim Gupta, Chief Operating Officer and Chief Financial Officer, UiPath.
"By co-creating next-gen AI-powered solutions with UiPath, HCLTech is setting new benchmarks for agentic autonomous operations that unlock unprecedented efficiency, agility and innovation for enterprises. Our proven expertise in hyperautomation, AI and cloud-first architectures helps us provide industry-specific and advanced automation solutions at scale," said Raghu Kidambi, Corporate Vice President and Global Head, Digital Process Operations, HCLTech.
About HCLTech
HCLTech is a global technology company, home to more than 223,000 people across 60 countries, delivering industry-leading capabilities centered around digital, engineering, cloud and AI, powered by a broad portfolio of technology services and products. We work with clients across all major verticals, providing industry solutions for Financial Services, Manufacturing, Life Sciences and Healthcare, Technology and Services, Telecom and Media, Retail and CPG and Public Services. Consolidated revenues as of 12 months ending March 2025 totaled $13.8 billion. To learn how we can supercharge progress for you, visit hcltech.com.
About UiPath
UiPath (NYSE: PATH) is a global leader in agentic automation, empowering enterprises to harness the full potential of AI agents to autonomously execute and optimize complex business processes. The UiPath Platform™ uniquely combines controlled agency, developer flexibility, and seamless integration to help organizations scale agentic automation safely and confidently. Committed to security, governance, and interoperability, UiPath supports enterprises as they transition into a future where automation delivers on the full potential of AI to transform industries. For more information, visit www.uipath.com.
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Contacts
For more information, please contact:
HCLTech
Meredith Bucaro, Americas
meredith-bucaro@hcltech.com
Elka Ghudial, EMEA
elka.ghudial@hcltech.com
James Galvin, APAC
james.galvin@hcltech.com
Nitin Shukla, India
nitin-shukla@hcltech.com
UiPath
Media Contact
pr@uipath.com
Investor Relations Contact
investor.relations@uipath.com
H Company Launches Next-Generation Autonomous AI Agents for Enterprise and Consumer Markets
PARIS - Tuesday, 03. June 2025 AETOSWire
H Company launches its next-generation European agent suite, comprising Runner H, Tester H, and Surfer H, and the open-sourcing of Holo-1 H, its cutting-edge visual-language model, lays the foundation for the next era of autonomous intelligence and artificial superintelligence.
Three products reflect H Company's vision to make a trusted, action-oriented AI that delivers task execution beyond traditional chatbots, achieving a 92.2% success rate, the state-of-the-art in computer-use technology while reducing costs by up to 5.5x against peers (OpenAI, Anthropic, Google).
The three AI agents cover task execution, web navigation and quality assurance, delivering faster task completion, GDPR-first data handling, and seamless hand-offs across the H-platform.
(BUSINESS WIRE)--H Company, a leading European AI Research and Product company backed by $220 million from tier-one investors, today announced the public launch of its autonomous AI agent platform featuring three specialized agents built to carry out complex digital tasks with human-in-the-loop.
The launch includes:
Runner H™, an orchestration platform for multi-step task completion,
Surfer H™, a web-native agent for browser-based automation,
Tester H™, an enterprise solution for automated software testing.
The company simultaneously open-sourced Holo-1, its proprietary visual-language model, in partnership with Hugging Face, Nvidia (NIM soon available) and AWS (Amazon).
Transforming AI from Assistants to Executors
H Company's current product selection supports its aim of making trusted, action-oriented AI agents available to organizations of all sizes. H Company's agents, which are built on proprietary multimodal models, bridge the gap by combining planning and vision capabilities to deliver measurable business outcomes.
“We are witnessing the transition from conversational AI to execution intelligence,” said Charles Kantor, Co-founder and Chairman of H Company. “Entering the era, where agents don’t just assist—they complete entire workflows autonomously, delivering the productivity gains enterprises have been seeking from AI investments."
Runner H
Runner H serves as H Company's flagship orchestration platform, delivering "intelligence in motion" by enabling users to accomplish complex, multi-step objectives through a single natural language prompt and is now available to the public.
Runner H dynamically coordinates specialized sub-agents and integrates with existing enterprise applications (including MCPs and agnostic interactions proprietary and additional agents), supporting seamless workflows across web browsers, document systems, and business applications while maintaining cost-effectiveness at scale.
Surfer H
Surfer H operates as a web-native automation agent, navigating browser environments with human-like precision while delivering cost-effective automation solutions. Unlike API-dependent solutions, Surfer H interacts directly with web interfaces, enabling deployment across any website without custom integrations or compatibility requirements, creating a powerful, general-purpose, cost-effective web automation system.
Tester H
Tester H addresses enterprise software testing challenges by converting natural language test scenarios into executable automated testing protocols. The platform supports both web and mobile applications, enabling teams to scale quality assurance processes without expanding technical testing resources.
Proven Performance Metrics
Benchmark testing demonstrates H Company's agents deliver superior cost-performance ratios and optimal value propositions compared to existing market solutions:
Surfer H achieved 92.2% task completion accuracy on the WebVoyager benchmark at just $0.13 per task, establishing the strongest tradeoff between accuracy and cost.
Performance exceeds that of major technology providers while reducing operational costs by up to 10 times, setting the Pareto frontier for performance-per-dollar.
Holo-1 visual-language model achieves 76.2% UI localization accuracy with affordable inference costs, leading performance among models under 7B parameters (the highest small-size model overall).
Open Source Strategy Accelerates Market Adoption
H Company's release of Holo-1 under Apache 2.0 licensing enables developers and enterprises to build production-ready custom automation solutions using visual AI capabilities. The model delivers commercial-grade accuracy for UI understanding and interaction.
The open-source initiative includes the WebClick dataset, featuring 1,639 real-world UI interaction scenarios designed to advance industry-wide development of visual AI applications.
Market Availability and Enterprise Adoption
Runner H is immediately available for public access, in waves, while Tester H targets enterprise customers requiring automated software testing capabilities. The platform's browser-based agent, Surfer H, ensures compatibility with existing enterprise privacy requirements, addressing key concerns for large-scale organizational deployment.
About H Company
H Company is a next-generation AI research and product company pioneering the future of autonomous, agentic AI. Founded to build intelligence that acts—not just reacts—H Company is creating the foundational infrastructure for autonomous AI systems that drive real-world outcomes across industries. With $220 million in funding, H Company is backed by leading global investors including Accel, Eric Schmidt and Yuri Milner.
To learn more, visit hcompany.ai.
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Contacts
Press
Mila Che
mila.che@agenceformat.com
+17189288517
Venture Global Launches Site Work at CP2 LNG Following Federal Approval
CP2 is Venture Global’s Third Facility to be Built in Last Five Years
Upon completion, Venture Global expected to become the largest LNG exporter in the United States, second largest in the world
Project expected to bring new LNG supply to global market beginning in 2027
(BUSINESS WIRE)--Venture Global, Inc. ($VG) announced today that it has initiated full mobilization and started site work at the company’s third LNG export facility, CP2 LNG. The launch of the site work comes shortly after CP2 received final approval and Notices to Proceed from the Federal Energy Regulatory Commission (FERC) on the Project, and weeks after receiving its non-FTA export authorization from the U.S. Department of Energy.
“Venture Global applauds the Commission and FERC staff for their continued work to advance critical U.S. energy projects like CP2 LNG that support our allies abroad and thousands of jobs here at home,” said Mike Sabel, CEO of Venture Global. “With all federal approvals now in hand we are excited to announce that we have launched on-site work for this Project, which is expected to deliver reliable low-cost LNG to the world starting in 2027. I am proud of our team and their relentless commitment to execution which has enabled our company’s historic achievements and rapid growth from a start-up to breaking ground on our third LNG export facility since 2019.”
CP2 is a strategically important project that is expected to provide U.S. LNG to customers in Europe, Japan and other allies around the world. The Project is expected to support approximately 3,000 new jobs in Louisiana – 400 of which will be direct, permanent employees of CP2 – and pay more than $4 billion in local property taxes during its operation. At peak construction, CP2 is expected to employ approximately 7,500 direct construction jobs and support tens of thousands of indirect subcontractor, part-time and full-time jobs in over 30 states.
Building off Venture Global’s “design one, build many” modularized LNG facility strategy, CP2 is already well advanced in engineering, procurement and contracting. Separate from the site work commencing now, the Project already has significant off-site work underway on the Project modules and equipment. This significant engineering and off-site progress now positions CP2 as one of the most advanced LNG export projects under development in the United States and we believe, once completed, will position Venture Global to become the top exporter of U.S. LNG.
About Venture Global
Venture Global is a long-term, low-cost provider of U.S. LNG sourced from resource rich North American natural gas basins. Venture Global’s business includes assets across the LNG supply chain including LNG production, natural gas transport, shipping and regasification. Venture Global’s first facility, Calcasieu Pass, commenced producing LNG in January 2022 and achieved commercial operations in April 2025. The company’s second facility, Plaquemines LNG, achieved first production of LNG in December 2024. The company is currently constructing and developing over 100 MTPA of nameplate production capacity to provide clean, affordable energy to the world. Venture Global is developing Carbon Capture and Sequestration projects at each of its LNG facilities.
Forward-looking Statements
This press release contains forward-looking statements. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). All statements, other than statements of historical facts, included herein are “forward-looking statements.” In some cases, forward-looking statements can be identified by terminology such as “may,” “might,” “will,” “could,” “should,” “expect,” “plan,” “project,” “intend,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “pursue,” “target,” “continue,” the negative of such terms or other comparable terminology.
These forward-looking statements, which are subject to risks, uncertainties and assumptions about us, may include statements about our future performance, our contracts, our anticipated growth strategies and anticipated trends impacting our business. These statements are only predictions based on our current expectations and projections about future events. There are important factors that could cause our actual results, level of activity, performance or achievements to differ materially from the results, level of activity, performance or achievements expressed or implied by the forward-looking statements. Those factors include our need for significant additional capital to construct and complete future projects and related assets, and our potential inability to secure such financing on acceptable terms, or at all; our potential inability to accurately estimate costs for our projects, and the risk that the construction and operations of natural gas pipelines and pipeline connections for our projects suffer cost overruns and delays related to obtaining regulatory approvals, development risks, labor costs, unavailability of skilled workers, operational hazards and other risks; the uncertainty regarding the future of global trade dynamics, international trade agreements and the United States’ position on international trade, including the effects of tariffs; our dependence on our EPC and other contractors for the successful completion of our projects, including the potential inability of our contractors to perform their obligations under their contracts; various economic and political factors, including opposition by environmental or other public interest groups, or the lack of local government and community support required for our projects, which could negatively affect the permitting status, timing or overall development, construction and operation of our projects; and risks related to other factors discussed under “Item 1A.—Risk Factors” of our annual report on Form 10-K for the year ended December 31, 2024 as filed with the Securities and Exchange Commission (“SEC”) and any subsequent reports filed with the SEC.
Any forward-looking statements contained herein speak only as of the date of this press release and are based on assumptions that we believe to be reasonable as of this date. We undertake no obligation to update these statements to reflect subsequent events or circumstances, except as may be required by law.
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Investors:
Ben Nolan
IR@ventureglobalLNG.com
Media:
Shaylyn Hynes
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Agenus and Zydus Lifesciences Enter $141M Strategic Collaboration to Advance BOT/BAL, Expand Zydus’ Biologics Manufacturing in the US
LEXINGTON, Mass. - Tuesday, 03. June 2025 AETOSWire
$75M upfront payment to Agenus for the transfer of manufacturing assets
$50M of contingent payments to Agenus
Exclusive license for BOT/BAL in India and Sri Lanka
$16M equity investment at $7.50 per share
(BUSINESS WIRE) -- Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, today announced it has signed definitive partnership agreements with Zydus Lifesciences Ltd. (NSE: ZYDUSLIFE), including its subsidiaries/affiliates, hereafter referred to as “Zydus,” designed to accelerate clinical development, scale global manufacturing, and expand patient access to botensilimab and balstilimab (BOT/BAL).
The strategic collaboration includes an exchange of Agenus’ state-of-the-art biologics CMC facilities in Emeryville, CA and Berkeley, CA for upfront consideration of $75M; Agenus to receive up to an additional $50M in contingent payments triggered by BOT/BAL production orders. Zydus, an India-based multinational pharmaceutical company with over 27,000 employees and operations in 55 countries, will launch a BioCDMO business using the facilities as their flagship U.S. sites to provide biologics contract manufacturing services to biopharmaceutical companies globally.
Agenus will become Zydus’ first BioCDMO customer through an exclusive manufacturing agreement for BOT/BAL to ensure the combination regimen’s BLA and launch readiness needs. This collaboration enables Agenus to unlock the value of its manufacturing assets and secure strategic capital to drive BOT/BAL toward global regulatory engagement and commercialization.
Agenus will also grant Zydus an exclusive license to develop and commercialize BOT and BAL in India and Sri Lanka, capitalizing on Zydus’ established local market presence and infrastructure. Zydus will pay Agenus a 5 percent royalty on net sales in those countries.
In a demonstration of mutual commitment, Zydus will also make a strategic equity investment in Agenus by purchasing approximately 2.1 million shares of common stock at $7.50 per share, totaling approximately $16 million in gross proceeds. Agenus intends to apply the net proceeds from the sale of the purchased shares for working capital and general corporate purposes, and will accelerate ongoing clinical development, registration and potential commercialization of BOT/BAL.
By uniting Agenus’ pioneering research and development capabilities with Zydus’ worldwide manufacturing, commercialization and operational strength, this partnership sets the stage for a new era in cancer immunotherapy in India and beyond.
“With a trade agreement between the United States and India seemingly imminent, there is a renewed sense of confidence by trading partners in both countries in the future of Indian-American relations,” said Dr. Garo Armen, CEO of Agenus. “There is also a growing recognition by both countries of the need for the United States to ensure that biopharma supply chains are secure. We are working with Zydus to accelerate future clinical trials for BOT/BAL and eventually its global footprint in oncology therapeutics. This agreement is an expression of confidence in the future of Agenus and in the regulatory environment of the United States. The administration has created an environment that has brought these two trading partners together. The United States is the second largest trading partner with India. For these reasons and the strong collaborative spirit we feel with our new partners at Zydus, we decided to enter into this partnership now.”
“We are thrilled to be partnering with Agenus to advance BOT/BAL, which has the potential to benefit thousands of patients in our core markets of India and Sri Lanka annually and millions of solid tumor patients globally. We plan to run clinical trials testing BOT/BAL in both early-stage and late-stage disease, along with expansion beyond colorectal cancer to other major disease settings like triple negative breast cancer,” said Dr. Sharvil Patel, Managing Director at Zydus Lifesciences Ltd.
The transaction is subject to customary closing conditions and satisfactory due diligence. The parties aim to complete closing agreements within 60 days.
Conference Call and Webcast
Date/Time: Tuesday, June 3rd; 4:30 p.m. ET
To access dial-in numbers, please register at: https://registrations.events/direct/Q4I127881000000000.
Conference ID: 12788
Advisors
As part of this effort, Agenus was advised by Biotech Value Advisors (BVA), a strategic advisory firm, which provided guidance on transaction structure, partner selection and negotiations.
About Agenus
Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels.
About Zydus Lifesciences
Zydus Lifesciences Ltd. with an overarching purpose of empowering people with freedom to live healthier and more fulfilled lives, is an innovative, global lifesciences company that discovers, develops, manufactures, and markets a broad range of healthcare therapies. The group employs over 27,000 people worldwide, including 1,400 scientists engaged in R&D, and is driven by its mission to unlock new possibilities in lifesciences through quality healthcare solutions that impact lives. The group aspires to transform lives through path-breaking discoveries. For more details visit www.zyduslife.com
About Botensilimab (BOT)
Botensilimab (BOT) is a human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.
Approximately 1,200 patients have been treated with botensilimab and/or balstilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov.
About Balstilimab (BAL)
Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in >900 patients to date and has demonstrated clinical activity and a favorable tolerability profile in several tumor types.
Forward-Looking Statements
This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2024, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.
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European Commission Approves ADCETRIS® (brentuximab vedotin) for the Treatment of Adult Patients with Newly Diagnosed Stage IIb/III/IV Hodgkin Lymphoma in Combination with ECADD
OSAKA, Japan & CAMBRIDGE, Mass.
- Approval Based on Positive Results from the Phase 3 HD21 Trial for Stage IIb with Risk Factors/III/IV Hodgkin Lymphoma
- ADCETRIS-based Combination Demonstrated Superior Safety Profile and Efficacy Compared to eBEACOPP, a Standard of Care Regimen in Europe
- Second Approval in Frontline Hodgkin Lymphoma Broadens ADCETRIS’ Therapeutic Reach, Adding to Six Previously Approved, Distinct Indications for ADCETRIS in the European Union
(BUSINESS WIRE) -- Takeda (TSE:4502/NYSE:TAK) today announced that the European Commission (EC) approved ADCETRIS® (brentuximab vedotin) in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (ECADD) – a chemotherapy regimen – in adult patients with newly diagnosed Stage IIb with risk factors/III/IV Hodgkin lymphoma. The decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on April 25, 2025.
The approval for this ADCETRIS-based combination regimen, known as BrECADD, in frontline Hodgkin lymphoma is based on the results of the randomized Phase 3 HD21 trial. The study met its co-primary safety and efficacy endpoints, with BrECADD demonstrating significantly superior safety as assessed by treatment-related morbidity (TRMB) and non-inferior progression-free survival (PFS) in comparison to escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (eBEACOPP), a standard of care treatment in Europe1.
“Today's approval represents a significant advancement for patients with Hodgkin lymphoma in the European Union,” said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda. "This approval reinforces the role of ADCETRIS as a backbone in the treatment of specific lymphomas, offering healthcare professionals greater flexibility to tailor treatment plans according to individual patient needs. We’re proud to contribute another impactful option for those diagnosed with this challenging disease.”
ADCETRIS is an antibody-drug conjugate (ADC) directed at CD30, a defining marker of Hodgkin lymphoma, and has been previously approved as a therapy for adult patients in the European Union (EU) in six distinct indications. This decision marks the second approval for an ADCETRIS-based combination regimen for frontline Hodgkin lymphoma, broadening the spectrum of available treatments for patients who historically have had limited options.
“With BrECADD, patients now have a treatment option that not only offers greater curative potential2* but also significantly reduces treatment-related morbidity compared to eBEACOPP,” said Peter Borchmann, MD, PhD, University Hospital of Cologne, Germany, and trial chairman of the HD21 study. “This new ADCETRIS-based combination therapy may offer a new standard of care for frontline treatment of adults with advanced stage Hodgkin lymphoma, contributing to improved long-term outcomes for patients.”
About the HD21 Trial
The HD21 study is a Phase 3, multi-country, prospective, open-label, randomized, multicenter trial conducted by the German Hodgkin Study Group (GHSG) with a PET-response adapted designed to assess the feasibility, efficacy, safety and tolerability of BrECADD, a novel, rationally designed, CD30-intensified frontline regimen for patients with advanced Hodgkin lymphoma.
Enrolled patients with newly diagnosed, Stage IIb with large mediastinal mass and/or extranodal lesions, Stage III or IV Hodgkin lymphoma were randomized to receive two cycles of either escalated BEACOPP or BrECADD, respectively, followed by interim PET staging. A decision is then made if patients received a further two or four cycles of escalated BEACOPP or BrECADD.
The HD21 trial aims to evaluate a new treatment regimen to minimize side effects, while maintaining similar responses to treatment. The study has co-primary endpoints: safety is assessed by treatment-related morbidity (TRMB) (superiority), a novel endpoint focused on clinically relevant, acute toxicities of primary chemotherapy, and efficacy is assessed by PFS (non-inferiority). Secondary endpoints are tumor response (complete response [CR] rate), overall survival (OS), infertility rate at one year, second malignancies, frequency of adverse events, therapy adherence and quality of life.
About ADCETRIS® (brentuximab vedotin)
ADCETRIS is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Pfizer’s proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.
ADCETRIS injection for intravenous infusion has received FDA approval for eight indications:
Adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL) in combination with doxorubicin, vinblastine, and dacarbazine (2018)
Pediatric patients 2 years and older with previously untreated high risk cHL in combination with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (2022)
Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation (2015)
Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates (2011)
Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone (2018)
Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen (2011)
Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy (2017)
Adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are not eligible for auto-HSCT or CAR T-cell therapy, in combination with lenalidomide and a rituximab product (2025)
Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression in 2017, adults with pcALCL or CD30-expressing MF who have had prior systemic therapy in 2018, for previously untreated Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in 2019, and for previously untreated adult patients with sALCL, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30, in combination with cyclophosphamide, doxorubicin, prednisone in 2019.
ADCETRIS received conditional marketing authorization from the European Commission in October 2012, and the specific obligations of the conditional marketing authorization were fulfilled in May 2022. The approved indications in the European Union are: (1) for the treatment of adult patients with previously untreated CD30-positive Stage III or IV Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine (AVD), (2) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (3) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (4) for the treatment of adult patients with relapsed or refractory sALCL, (5) for the treatment of adult patients with previously untreated sALCL in combination with CHP, (6) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (7) for the treatment of adult patients with previously untreated CD30+ Stage IIB with risk factors, Stage III or Stage IV HL in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD).
ADCETRIS has received marketing authorization by regulatory authorities in 80 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See Important Safety Information below.
ADCETRIS is being evaluated broadly in more than 70 clinical trials, including a Phase 3 study in first-line Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in first-line CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies.
Pfizer and Takeda fund joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.
ADCETRIS (brentuximab vedotin) Important Safety Information (European Union)
Please refer to Summary of Product Characteristics (SmPC) before prescribing.
Contraindications
ADCETRIS is contraindicated for patients with hypersensitivity to brentuximab vedotin and its excipients. Combined use of bleomycin and ADCETRIS causes pulmonary toxicity.
Special Warnings and Precautions
Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Progressive multifocal leukoencephalopathy (PML): John Cunningham virus (JCV) reactivation resulting in PML and death can occur in ADCETRIS-treated patients. PML has been reported in patients who received this treatment after receiving multiple prior chemotherapy regimens. PML is a rare demyelinating disease of the central nervous system that results from reactivation of latent JCV and is often fatal.
Patients should be closely monitored for new or worsening neurological, cognitive, or behavioral signs or symptoms, which may be suggestive of PML. ADCETRIS should be held for any suspected case of PML. Suggested evaluation of PML includes neurology consultation, gadolinium-enhanced magnetic resonance imaging of the brain and cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or a brain biopsy with evidence of JCV. A negative JCV PCR does not exclude PML. Additional follow up and evaluation may be warranted if no alternative diagnosis can be established. ADCETRIS dosing should be permanently discontinued if a diagnosis of PML is confirmed.
The physician should be particularly alert to symptoms suggestive of PML that the patient may not notice (e.g., cognitive, neurological, or psychiatric symptoms).
Pancreatitis: Acute pancreatitis has been observed in patients treated with ADCETRIS. Fatal outcomes have been reported.
Patients should be closely monitored for new or worsening abdominal pain, which may be suggestive of acute pancreatitis. Patient evaluation may include physical examination, laboratory evaluation for serum amylase and serum lipase, and abdominal imaging, such as ultrasound and other appropriate diagnostic measures. ADCETRIS should be held for any suspected case of acute pancreatitis. ADCETRIS should be discontinued if a diagnosis of acute pancreatitis is confirmed.
Pulmonary Toxicity: Cases of pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), some with fatal outcomes, have been reported in patients receiving ADCETRIS. Although a causal association with ADCETRIS has not been established, the risk of pulmonary toxicity cannot be ruled out. In the event of new or worsening pulmonary symptoms (e.g. cough, dyspnoea), a prompt diagnostic evaluation should be performed and patients should be treated appropriately. Consider holding ADCETRIS dosing during evaluation and until symptomatic improvement.
Serious infections and opportunistic infections: Serious infections such as pneumonia, staphylococcal bacteremia, sepsis/septic shock (including fatal outcomes), and herpes zoster, cytomegalovirus (CMV) (reactivation) and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with ADCETRIS. Patients should be carefully monitored during treatment for the emergence of possible serious and opportunistic infections.
Infusion-related reactions (IRR): Immediate and delayed IRR, as well as anaphylaxis, have been reported with ADCETRIS.
Patients should be carefully monitored during and after infusion. If an anaphylactic reaction occurs, administration of ADCETRIS should be immediately and permanently discontinued and appropriate medical therapy should be administered.
If an IRR occurs, the infusion should be interrupted and appropriate medical management instituted. The infusion may be restarted at a slower rate after symptom resolution. Patients who have experienced a prior IRR should be premedicated for subsequent infusions. Premedication may include paracetamol, an antihistamine and a corticosteroid.
IRRs are more frequent and more severe in patients with antibodies to brentuximab vedotin.
Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS. Patients with rapidly proliferating tumour and high tumour burden are at risk of tumour lysis syndrome. These patients should be monitored closely and managed according to best medical practice. Management of TLS may include aggressive hydration, monitoring of renal function, correction of electrolyte abnormalities, anti-hyperuricaemic therapy, and supportive care.
Peripheral neuropathy (PN): ADCETRIS may cause peripheral neuropathy, both sensory and motor. ADCETRIS-induced peripheral neuropathy is typically an effect of cumulative exposure to this medicinal product and is reversible in most cases. In clinical trials, the majority of patients had resolution or improvement of their symptoms. Patients should be monitored for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paraesthesia, discomfort, a burning sensation, neuropathic pain or weakness. Patients experiencing new or worsening peripheral neuropathy may require a delay and a dose reduction of ADCETRIS or discontinuation of treatment.
Hematological toxicities: Grade 3 or Grade 4 anaemia, thrombocytopenia, and prolonged (≥ 1 week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose.
Febrile neutropenia: Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection with an absolute neutrophil count < 1.0 x 109/L, fever ≥ 38.5 0C; ref CTCAE v3) has been reported with treatment with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose of treatment. Patients should be monitored closely for fever and managed according to best medical practice if febrile neutropenia develops.
In combination therapy with AVD or CHP, advanced age was a risk factor for febrile neutropenia. When ADCETRIS is administered in combination with AVD or CHP, primary prophylaxis with G-CSF, beginning with the first dose, is recommended for all adult patients regardless of age. In combination therapy with AVD or CHP, advanced age was a risk factor for febrile neutropenia.
Severe cutaneous adverse reactions (SCARs): Cases of SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with ADCETRIS. Fatal outcomes have been reported for SJS and TEN. If SJS, TEN or DRESS occur, ADCETRIS should be discontinued, and appropriate medical therapy should be administered.
Gastrointestinal (GI) Complications: GI complications including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorrhage, some with fatal outcomes, have been reported in patients treated with ADCETRIS. In the event of new or worsening GI symptoms, perform a prompt diagnostic evaluation and treat appropriately.
Hepatotoxicity: Hepatotoxicity in the form of elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) has been reported with ADCETRIS. Serious cases of hepatotoxicity, including fatal outcomes, have also occurred. Pre-existing liver disease, comorbidities, and concomitant medications may also increase the risk. Liver function should be tested before initiating the treatment and routinely monitored in patients receiving ADCETRIS. Patients experiencing hepatotoxicity may require a delay, change in dose or discontinuation of ADCETRIS.
Hyperglycemia: Hyperglycaemia has been reported during clinical trials in patients with an elevated Body Mass Index (BMI) with or without a history of diabetes mellitus. However, any patient who experiences an event of hyperglycaemia should have their serum glucose closely monitored. Anti-diabetic treatment should be administered as appropriate.
Infusion site extravasation: Extravasation during intravenous infusion has occurred. Given the possibility of extravasation, it is recommended to closely monitor the infusion site for possible infiltration during drug administration.
Renal and Hepatic Impairment: There is limited experience in patients with renal and hepatic impairment. Available data indicate that MMAE clearance might be affected by severe renal impairment, hepatic impairment, and by low serum albumin concentrations.
CD30+ CTCL: The size of the treatment effect in CD30 + CTCL subtypes other than mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) is not clear due to lack of high level evidence. In two single arm phase II studies of ADCETRIS, disease activity has been shown in the subtypes Sézary syndrome (SS), lymphomatoid papulosis (LyP) and mixed CTCL histology. These data suggest that efficacy and safety can be extrapolated to other CTCL CD30+ subtypes. Nevertheless, ADCETRIS should be used with caution in other CD30+ CTCL patients after careful consideration of the potential benefit-risk on an individual basis.
Sodium content in excipients: This medicinal product contains 13.2 mg sodium per vial, equivalent to 0.7% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Polysorbate content in excipients: This medicinal product contains 2 mg of polysorbate 80 per vial, equivalent to 0.2 mg/ml. Polysorbates may cause allergic reactions.
Interactions
Interaction with medicinal products metabolised through CYP3A4 route (CYP3A4 inhibitors/inducers)
Co‑administration of brentuximab vedotin with ketoconazole, a strong CYP3A4 and P‑gp inhibitor, increased the exposure to the antimicrotubule agent MMAE by approximately 73%, and did not alter the plasma exposure to brentuximab vedotin. Therefore, co‑administration of brentuximab vedotin with strong CYP3A4 and P‑gp inhibitors may increase the incidence of neutropenia. If neutropenia develops, refer to Tables 1 and 2 for dosing recommendations for neutropenia.
Co‑administration of brentuximab vedotin with rifampicin, a strong CYP3A4 inducer, did not alter the plasma exposure to brentuximab vedotin. Though PK data are limited, co‑administration of rifampicin appeared to reduce plasma concentrations of MMAE metabolites that could be assayed.
Co‑administration of midazolam, a CYP3A4 substrate, with brentuximab vedotin did not alter the metabolism of midazolam; therefore brentuximab vedotin is not expected to alter the exposure to medicines that are metabolized by CYP3A4 enzymes.
Etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD regimen)
The pharmacokinetics of ADC and MMAE have not been characterized in the setting of BrECADD. Exposures of brentuximab vedotin and concurrent chemotherapy are not expected to be affected in the BrECADD regimen.
Fertility, pregnancy and lactation
Women of childbearing potential: Women of childbearing potential should be using two methods of effective contraception during treatment with ADCETRIS and until 6 months after treatment.
Pregnancy: There are no data from the use of ADCETRIS in pregnant women. Studies in animals have shown reproductive toxicity. ADCETRIS should not be used during pregnancy unless the benefit to the mother outweighs the potential risks to the fetus. If a pregnant woman needs to be treated she should be clearly advised on the potential risk to the fetus.
Breast-feeding: There is no data as to whether brentuximab vedotin or its metabolites are excreted in human milk. A risk to the newborn/infant cannot be excluded. A decision should be made whether to discontinue breast-feeding or to discontinue/abstain from this therapy, taking into account a potential risk of breast-feeding for the child and the benefit of therapy for the woman.
Fertility: In non-clinical studies, brentuximab vedotin treatment has resulted in testicular toxicity, and may alter male fertility. MMAE has been shown to have anagenic properties. Therefore, men being treated with this medicine are advised to have sperm samples frozen and stored before treatment. Men being treated with this medicine are advised not to father a child during treatment and for up to 6 months following the last dose.
Effects on ability to drive and use machines: ADCETRIS may have a moderate influence on the ability to drive and use machines (e.g. dizziness).
Undesirable Effects
Monotherapy: The most frequent adverse reactions (≥10%) were infections, peripheral sensory neuropathy, nausea, fatigue, diarrhea, pyrexia, upper respiratory tract infection, neutropenia, rash, cough, vomiting, arthralgia, peripheral motor neuropathy, infusion-related reactions, pruritus, constipation, dyspnea, weight decreased, myalgia and abdominal pain. Serious adverse drug reactions occurred in 12% of patients. The frequency of unique serious adverse drug reactions was ≤1%. Adverse events led to treatment discontinuation in 24% of patients.
Combination Therapy: In the studies of ADCETRIS as combination therapy in 662 patients with previously untreated advanced HL and 223 patients with previously untreated CD30+ PTCL, the most common adverse reactions (≥ 10%) were: infections, neutropenia, peripheral sensory neuropathy, nausea, constipation, vomiting, diarrhea, fatigue, pyrexia, alopecia, anemia, weight decreased, stomatitis, febrile neutropenia, abdominal pain, decreased appetite, insomnia, bone pain, rash, cough, dyspnea, arthralgia, myalgia, back pain, peripheral motor neuropathy, upper respiratory tract infection, and dizziness. In patients receiving ADCETRIS combination therapy, serious adverse reactions occurred in 34% of patients. Serious adverse reactions occurring in ≥ 3% of patients included febrile neutropenia (15%), pyrexia (5%), and neutropenia (3%). Adverse events led to treatment discontinuation in 10% of patients.
In patients receiving ADCETRIS combination therapy, serious adverse reactions occurred in 34% of patients. Serious adverse reactions occurring in ≥ 3% of patients included febrile neutropenia (15%), pyrexia (5%), and neutropenia (3%). Adverse events led to treatment discontinuation in 10% of patients.
Adverse events led to treatment discontinuation in 10% of patients. Adverse events that led to treatment discontinuation in ≥ 2% of patients included peripheral sensory neuropathy, and peripheral neuropathy.
Combination Therapy (BrECADD regimen): In the HD21 study, 747 patients received BrECADD, and 741 patients received eBEACOPP. The safety profile of ADCETRIS in patients receiving BrECADD remained consistent with other combination therapy (AVD/CHP).
Serious adverse reactions occurred in 39.4% patients receiving BrECADD treatment, and 36.4% in patients who received eBEACOPP. The most common serious adverse reactions in patients who received BrECADD (> 3%) were febrile neutropenia (19.3%), pyrexia (3.9%), and neutropenia (3.2%).
Serious cardiac adverse reactions occurred in 2.7% of patients receiving BrECADD and 1.1% of patients receiving eBEACOPP. The most common serious cardiac adverse reaction in patients who received BrECADD (>0.5%) was tachycardia (0.9%).
Serious adverse events led to treatment discontinuation in 2% of patients in both BrECADD and eBEACOPP arms. The most common serious adverse events that led to discontinuation in the BrECADD arm were febrile neutropenia (0.3%) and cardiac failure (0.3%).
ADCETRIS® (brentuximab vedotin) for injection U.S. Important Safety Information
BOXED WARNING
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML, and death can occur in ADCETRIS-treated patients.
CONTRAINDICATION
Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
WARNINGS AND PRECAUTIONS
Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS.
Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.
Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL, and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL.
Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.
Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections.
Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures.
Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment. Avoid use in patients with severe renal impairment.
Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment.
Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.
Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with pre-existing GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.
Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.
Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS.
ADVERSE REACTIONS
The most common adverse reactions (≥20%) in adult patients are peripheral neuropathy, nausea, fatigue, musculoskeletal pain, constipation, diarrhea, vomiting, pyrexia, upper respiratory tract infection, mucositis, abdominal pain, and rash. The most common laboratory abnormalities (≥20%) in adult patients are decreased neutrophils, increased creatinine, decreased hemoglobin, decreased lymphocytes, increased glucose, increased ALT, and increased AST.
The most common Grade ≥3 adverse reactions (≥5%) in combination with AVEPC in pediatric patients were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection.
DRUG INTERACTIONS
Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions.
USE IN SPECIAL POPULATIONS
Lactation: Breastfeeding is not recommended during ADCETRIS treatment.
Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here.
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 www.takeda.com.
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Medical Information
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Footnotes:
*While late relapse is rare, PFS status after 5 years does not guarantee cure. Patients should be monitored and encouraged to report any return of symptoms as appropriate.
References:
Borchmann P, Ferdinandus J, Schneider G, et al. Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial [published correction appears in Lancet. 2024 Nov 30;404(10468):2164. doi: 10.1016/S0140-6736(24)02571-6.]. Lancet. 2024;404(10450):341-352.
Bröckelmann PJ, Goergen H, Kohnhorst C, von Tresckow B, Moccia A, Markova J, Meissner J, Kerkhoff A, Ludwig WD, Fuchs M, Borchmann P, Engert A. Late Relapse of Classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7 to HD12 Trials. J Clin Oncol. 2017 May 1;35(13):1444-1450. doi: 10.1200/JCO.2016.71.3289. Epub 2017 Feb 27. PMID: 28240973.
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Contacts
Takeda Media Contacts:
Japanese Media
Tsuyoshi Tada
Tsuyoshi.tada@takeda.com
U.S. and International Media
Lauren Sherman
Lauren.leedberg@takeda.com
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