Cheryl Barton is director of PharmaVision, 

Cheryl Barton

Landkarte *** Europa | Image credit: ©beugdesign - Stock.adobe.com

On 2 July 2025, the European Commission (EC) announced a “bold and ambitious” new life science strategy to position the European Union (EU) as the world’s most attractive place for life sciences by 2030 (1). This strategy aims to positively impact public health, create jobs, and provide access to innovative, environmentally friendly technologies, thereby enhancing the EU's strategic resilience. Previously, President Ursula von der Leyen emphasized that the strategy for European life sciences was a priority in the political guidelines for 2024–2029, stating that, “we need to put research and innovation at the heart of our economy” (2). In January 2025, the EC also published the Competitiveness Compass, focusing on how to improve research and innovation (R&I) to boost competitiveness and promote innovation in biotechnology (3).

The EC has identified several strengths, including the presence of biotech clusters and leading academic institutions that operate with freedom and encourage diversity and inclusion. Additionally, the EU ranks second behind the United States (US) in terms of global high-value patents, holding 18% share of patents compared to 39% in the US (1). The life science industry continues to invest heavily in R&I, with 15% of the world’s top firms residing in the EU (1). However, the EC also recognizes that to improve R&I it must overcome numerous barriers, such as turning scientific breakthroughs into real-world applications, improving scalability in the EU, creating a more cohesive R&D ecosystem, utilizing healthcare data and artificial intelligence (AI) more effectively, and streamlining the regulatory process to reduce complexity and duplication (1).

How will this strategy unlock Europe’s life science potential?

To overcome these issues and achieve the life science strategy goals, the EC has outlined three interconnected phases that will impact the entire life science value chain:

optimising the R&I ecosystem to achieve a globally competitive life science sector

ensuring smooth and rapid market access for life science innovations

boosting the uptake and use of life science innovation.

The EC recognizes the need to optimize the R&I ecosystem and develop a globally competitive life science sector. This can be achieved through enhanced cooperation, more efficient resource use, and a comprehensive approach that leverages data and AI, develops adequate skills, and promotes a sustainable industry. The EC will provide new incentives for long-term multi-country clinical trials and rare disease research, strengthen EU bioclusters, and establish a network of European Centres of Excellence in advanced therapy medicinal products (ATMPs) (4). The EC also aims to establish a European Life Sciences R&I Data Assembly to improve cross-regulatory collaboration and enhance the interpretation of data regulations (5).

To ensure life science innovations reach the market smoothly and quickly, the European Medicines Agency (EMA) will need to establish more innovation-friendly regulations, and the EU will need to increase investments from both private and public sectors. A number of legislative changes and regulatory reforms are underway to simplify and modernize the approval processes, such as the Biotech Act and the EU Pharma Package, and these should help make the EU’s regulatory environment more conducive to biotech innovation (5–6). For instance, the Biotech Act, announced in July 2024, seeks to tackle barriers through legislative and policy changes across five key areas: regulation, financing, scale, skills, and data (7).

The creation of new knowledge is an essential basis for a vibrant life sciences ecosystem and for the development of technologies and innovations. The EC will invest more than €10 billion (US$11.9 billion) in various programs, such as Digital Europe, EU4Health, and Horizon Europe, to help build this knowledge base (8–10). Meanwhile, Member States and stakeholders must strengthen their connection with citizens to help reduce misinformation and build trust. They also need to collaborate more closely with end-users to ensure solutions meet their specific needs. Overall, this should help accelerate the adoption and use of life science innovations (1).

What is the future outlook for EU life sciences?

Although the EU is currently in a strong R&I position, the biotechnology sector remains highly competitive. In recent years, China has increased biotech investments following regulatory reforms, improvements in domestic manufacturing, and the implementation of the Healthy China 2030 initiative (11). Additionally, the implementation of US–EU framework on an agreement for reciprocal, fair, and balanced trade has resulted in a 15% tariff on pharmaceutical raw ingredients, APIs, and completed drug products imported into the US. This has raised expenses for branded pharmaceuticals developed by multinational corporations and created market uncertainty. Private investors are concerned that potential investments may slow due to pricing pressures, and biotech companies may hesitate to invest in new projects to expand operations, given the risks associated with tariffs (12–13).

Now more than ever, the EU needs to boost its investment in the life sciences sector and tackle longstanding issues that have hindered the region’s competitiveness and limited European patients' access to the latest treatments. Plans to introduce the Biotech Act in 2025, along with enhanced support for small and medium-sized enterprises and improvements to the regulatory framework, are positive developments. The European Federation of Pharmaceutical Industries and Association (EFPIA) welcomed the news; although, Nathalie Moll, Director General of EFPIA, warned that “for Europe to truly lead, it needs to invest in medicines, attract investment, accelerate turning that investment into new treatments and economic growth, and ensure that patients across the EU have access to them at the same pace as other regions” (14).

EC. A Competitiveness Compass for the EU 

Five Facts to Know: EU Life Sciences Strategy

. https://www.edelmanglobaladvisory.com. 2 July 2025. https://www.edelmanglobaladvisory.com/insights/five-facts-know-eu-life-sciences-strategy

 May 2025. https://www.europarl.europa.eu/RegData/etudes/BRIE/2025/772866/EPRS_BRI(2025)772866_EN.pdf

The New EU “Pharma Package”: Preparing for the Trilogue

. Crowell.com. 30 June 2025. https://www.crowell.com/en/insights/client-alerts/the-new-eu-pharma-package-preparing-for-the-trilogues

European Commission Sets Out New EU Life Sciences Strategy

. 1 Aug. 2025. https://www.osborneclarke.com/insights/european-commission-sets-out-new-eu-life-sciences-strategy

EU4Health Programme 2021-2027–A Vision for a Healthier European Union

. EC.europa.eu. (accessed 30 Sept. 2025). https://health.ec.europa.eu/funding/eu4health-programme-2021-2027-vision-healthier-european-union_en

(accessed 30 Sept. 2025). https://research-and-innovation.ec.europa.eu/funding/funding-opportunities/funding-programmes-and-open-calls/horizon-europe_en

Healthy China 2030: A Vision for Health Care

. https://www.ispor.org/docs/default-source/publications/newsletter/commentary_health-care_china_2030.pdf

Assessing the Impact of Tariffs on the Pharmaceutical Industry

. https://www.pharmafocuseurope.com/articles/impact-of-tariffs-on-pharmaceutical-industry.

The Impact of Tariffs on the Life Sciences Industry - Healthcare & Life Sciences Blog

31 Mar. 2025. https://healthcarelifesciences.bakermckenzie.com/2025/03/13/the-impact-of-tariffs-on-the-life-sciences-industry/

EU Life Science Strategy: A Springboard for European Life Sciences

. Efpia.eu. 2 July 2025. https://www.efpia.eu/news-events/the-efpia-view/statements-press-releases/eu-life-science-strategy-a-springboard-for-european-life-sciences/

Cheryl Barton is the founder and director of PharmaVision, Pharmavision.co.uk.

Articles

The European Commission has unveiled a comprehensive life science strategy to establish the EU as a global leader in life sciences by 2030. This initiative aims to enhance public health, create jobs, and foster innovation through environmentally friendly technologies. The strategy focuses on optimizing the research and innovation ecosystem, ensuring rapid market access for innovations, and increasing the adoption of life science advancements. Key measures include regulatory reforms, increased investments, and the establishment of European Centres of Excellence. The strategy also addresses challenges such as scalability, data utilization, and regulatory complexity.

The European Union aims to become the most attractive place for life science by 2030.

European Union Life Science Strategy

Digital composite of highlighted red painful liver of woman | Image credit: ©

Metabolic dysfunction-associated steatohepatitis (MASH) is a type of non-alcoholic fatty liver disease (NAFLD) affecting more than 250 million people worldwide, and the number of cases in advanced stages is expected to double by 2030. Underlying conditions such as obesity, type 3 diabetes, and metabolic syndrome can increase the risk of MASH. For many years, MASH has been difficult to treat, and several products have failed in clinical development, including Genfit’s peroxisome proliferator-activated receptor (PPAR) agonist elafibranor, Gilead's ASK1 inhibitor selonsertib, Intercept Pharmaceuticals' farnesoid X receptor (FXR) agonist obeticholic acid, and Novartis/Conatus' pan-caspase inhibitor emricasan.

In the past few years, significant progress has been made, and new products have entered the MASH market. In March 2024, the US Food and Drug Administration (FDA) approved Madrigal Pharmaceuticals’ orally active, selective thyroid hormone receptor (THR)-β agonist, Rezdiffra (resmetirom), for adults with MASH with moderate to advanced liver scarring (fibrosis), alongside diet and exercise (1). In June 2025, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) recommended granting conditional marketing authorization for Rezdiffra in MASH (2). On 19 Aug. 2026, the European Commission approved Rezidiffra, and the company is planning its first European launch in Germany in the fourth quarter of 2025 (3, 4).

In August 2025, Novo Nordisk received FDA approval for its injectable weight-loss drug Wegovy (semaglutide) for patients with MASH and moderate to advanced liver fibrosis, without cirrhosis, in combination with a reduced-calorie diet and exercise (5). The conditional clearance was based on Phase III results, where the glucagon-like peptide-1 receptor agonist (GLP-1RA) demonstrated improved liver scarring without worsening the condition and resolved MASH without making scarring worse (6,7). Eli Lilly is also seeking approval for its injectable dual-action gastric inhibitory polypeptide (GIP)/GLP-1RA, Zepbound (tirzepatide), based on its Phase II SYNERGY-MASH trial in patients with and without type 2 diabetes, and with stage 2 or 3 fibrosis (scarring) (8).

What investments are Big Pharma making in MASH?

MASH is seen as the next frontier in metabolic diseases, and numerous clinical trials are underway evaluating hormone analogs, receptor agonists, and enzyme inhibitors 

MASH drug development has attracted significant interest from pharma and private investors. In the GLP-1 space, Boehringer Ingelheim has teamed up with UK-based Zealand Pharma to develop survodutide. This dual glucagon/GLP-1 agonist has demonstrated a placebo-adjusted 64.8% improvement in fatty liver disease (9).

Table I. Clinical development of therapies targeting Metabolic dysfunction-associated steatohepatitis (MASH).

Table I. Clinical development of therapies targeting Metabolic dysfunction-associated steatohepatitis (MASH) (Continued).

In May 2025, GSK acquired Boston Pharmaceuticals' lead asset efimosfermin for US$1.2 billion plus US$800 million in milestone payments. Efimosfermin is a novel, once-monthly fibroblast growth factor 21 (FGF21) analog therapeutic in Phase II clinical development for the treatment of MASH (10). US-based Akero Therapeutics and 89bio are also developing FGF21 analogs, efruxifermin and pegozafermin, respectively (11, 12).

Which European frontrunners are targeting MASH?

Several European biotechs are developing innovative approaches to target the underlying cause of MASH and liver fibrosis. These include:

focuses on developing novel small-molecule therapies targeting fibrosis, lysosomal storage disorders, and oncology. Its lead program, lanifibranor (IVA337), is an orally active pan-PPAR agonist. It demonstrated promising results in a Phase IIb placebo-controlled trial in patients with active MASH, improving the resolution of MASH without worsening fibrosis (13). Lanifibranor is currently being evaluated in NATiV3, a pivotal Phase III clinical trial in patients with MASH and fibrosis stages F2 and F3; the trial is due to complete in September 2026 (14).

 is a clinical-stage biopharmaceutical company specializing in fibrolytic and anti-inflammatory diseases. Its lead compound, Vonafexor, is an orally active, non-steroidal agonist of NR1H4 (FXR, or bile acid receptor). In the Phase II LIVIFY study, Vonafexor significantly reduced liver fibrosis and inflammation markers, decreased liver fat and weight, and improved liver and kidney functions (15). In January 2024, the company raised €39 million (US$45.39 million) in Series C funding to develop Vonafexor further (16).

, is a biotechnology company focused on discovering and developing innovative peptide-based medicines. It has created several candidates targeting the metabolic brain axis, including Survodutide, a glucagon/GLP-1 dual agonist, which is being developed with Boehringer Ingelheim for MASH (Phase II) and obesity (Phase II), and petrelintide, an amylin analogue that it is co-developing with Roche. This compound could represent a new class of treatment for obesity (17).

In the United States, several biotech companies are working on MASH candidates, including MetaVia, which is developing DA-1726, a novel oxyntomodulin (OXM) analogue that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist (18).

Additionally, significant progress has been made in developing biomarkers and diagnostics to identify patients at risk of MASH. For example, France-based Genfit has created a non-invasive diagnostic program that includes an 

test to detect NIS4+ and NIS2+. At the same time, Nordic Bioscience has identified biomarkers targeting neo-epitopes of collagen fragments that can be used to risk-stratify patients. (19, 20).

The global MASH market was valued at US$7.9 billion in 2024 and is forecast to grow to US$31.8 billion by 2033, with a compound annual growth rate of 17.7% from 2025 to 2033 (21). After many failed attempts, the industry has finally identified new ways to reduce liver fat buildup. While Madrigal's orally active Rezdiffra was the first to enter the US and European Union markets, it now faces competition from Novo’s injectable Wegovy, and Eli Lilly is not far behind. It will be interesting to see how the MASH landscape evolves and whether new approaches, such as oxyntomodulin analogues and gene silencing agents, can capture a share of this lucrative market in the future.

FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease

Madrigal Receives European Commission Approval for Rezdiffra™ (resmetirom) for the Treatment of MASH with Moderate to Advanced Liver Fibrosis.

Madrigal Pharmaceuticals Reports Second-Quarter 2025 Financial Results and Provides Corporate Updates.

FDA Approves Treatment for Serious Liver Disease Known as ‘MASH’

Sanyal, A. J.; Newsome, P. N.; Kliers, I.; et al.

 Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis

Semaglutide 2.4 mg Demonstrates Superior Improvement in Both Liver Fibrosis and MASH Resolution in the ESSENCE Trial.

Loomba, R.; Hartman, M. L.; Lawitz, E. J.; et al. (2024). T

irzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis

Survodutide US FDA Breakthrough Therapy Phase 3 Trials MASH.

GSK. GSK to Acquire Efimosfermin, a Phase III-Ready Potential Best-in-Class Specialty Medicine to Treat and Prevent Progression of Steatotic Liver Disease (SLD). Press Release. 14 May 2025.

 akerotx.com/clinical-trials (accessed 20 Aug. 2025).

89bio Receives EMA PRIME Status for Pegozafermin in the Treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH) with Fibrosis and Compensated Cirrhosis.

Francque, S. M.; Bedossa, P.; Ratziu, V.; et al.. 

A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH. 

ClinicalTrials.gov. Study Details | A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 ) (accessed 21 August 2025).

Ratziu, V.; Harrison, S. A.; Loustaud-Ratti; et al. 

Hepatic and Renal Improvements with FXR Agonist Vonafexor in Individuals with Suspected Fibrotic NASH. 

ENYO Pharma. ENYO Pharma Announces a €39 Million Series C Financing and FDA Clearance to Advance Vonafexor in a Phase 2 Clinical Trial for Patients with Alport syndrome. Press Release. 3 Jan. 2024.

MetaVia Doses First Patient in the 48 mg MAD Cohort of Its Phase 1 Clinical Trial Evaluating DA-1726 for the Treatment of Obesity to Further Explore Maximum Tolerated Dose.

Nash Or Mash Treatment Market Growth Rate, Industry Insights and Forecast 2025-2033

Cheryl Barton, PhD, is founder and director of PharmaVision, Pharmavision.co.uk.

Editor's note: The references in this article have been updated. 

Metabolic dysfunction-associated steatohepatitis (MASH), a subtype of non-alcoholic fatty liver disease, is projected to see a significant increase in advanced cases by 2030. Recent advancements include FDA and EMA approvals of Madrigal Pharmaceuticals' Rezdiffra and Novo Nordisk's Wegovy for MASH treatment. Big Pharma is heavily investing in MASH, with companies like GSK acquiring assets and others developing innovative therapies. European biotechs are also making strides with novel treatments. The MASH market is expected to grow substantially, driven by new therapeutic approaches and diagnostic advancements.

Novo Nordisk’s Wegovy will be competing with Madrigal Pharmaceuticals’ Rezdiffra in the metabolic dysfunction-associated steatohepatitis arena. 

Competition in MASH Is Heating Up as GLP-1s Gate-Crash the Party

In March 2025, the European Medicines Agency (EMA) published a three-year work plan (2025–2027) for the Good Manufacturing and Distribution Practice (GMDP) Inspectors Working Group (IWG), focusing on the Network Strategy and Regulatory Science Strategy (RSS) goals. The work plan emphasized the importance of supply chain integrity and resilience, product quality, and the potential impact of new manufacturing technologies on the supply chain(1). The overall objectives of the plan included:

Analyze the possible implications of new manufacturing technologies to regulate the new supply chains needed

Enhance inspector capacity building at the European Union and international levels

Enhance traceability, oversight, and security in the human/veterinary medicine supply chain

Encourage supply chain resilience and review long-term risks resulting from dependency on a limited number of manufacturers and sites

Reinforce the responsibility for product quality by harmonising and reinforcing guidance (1).

On 7 July 2025, the GMDP-Inspectors Working Group, in cooperation with the Pharmaceutical Inspection Co-operation Scheme (PIC/S), launched a public consultation regarding the revision of the EU’s good manufacturing practice (GMP) guidelines

, Annex 11 and Chapter 4, along with the introduction of a dedicated Annex 22 on artificial intelligence (AI) (2). The revision of Chapter 4 and Annex 11 will expand the scope of documentation requirements and raise the bar on digital system validation and oversight. Whilst the addition of Annex 22 sets clear boundaries for the safe and acceptable use of AI and machine learning (ML) in a regulated GMP environment, it will help to ensure regulatory harmonization in the manufacturing of medicines (3).

The revised Chapter 4 includes changes that emphasize the importance of documentation in GMP compliance and support the adoption of new technologies, hybrid solutions, and services for managing documentation (4). Risk-management principles are now central and integrated into the data governance system to ensure the accuracy, integrity, availability, and readability of documents in all formats. All documentation, whether in text, image, video, or audio form, must remain complete and legible throughout its lifecycle. The guideline also clarifies the requirements for managing electronic records, signatures, and data integrity, and aligns with the recent revision of Annex 11.

The revised Annex 11 establishes improved requirements for managing the entire lifecycle of computerized systems, requiring that quality risk management (QRM) principles be thoroughly applied at all stages to ensure product quality, patient safety, and data integrity. The updated provisions strengthen obligations related to defining and continuously maintaining system requirements, as well as overseeing suppliers and external service providers (5). Additionally, the Annex enhances controls for ensuring data integrity, audit trails, electronic signatures, system security, as well as backup and archiving.

The new annex on AI sets requirements for using AI/ML in manufacturing active substances and medicinal products (6). It details how to select, train, and validate AI models and places emphasis on defining the intended use of the model, establishing performance metrics, ensuring the quality of training data, and managing test data. Annex 22 requires ongoing oversight of AI systems, including change control, performance monitoring, and procedures for human review when needed. The document does not apply to generative AI and large language models, and these models should not be used in critical GMP applications.

By 2026, the updates to Chapter 4 and Annex 11, along with the introduction of Annex 22, will bring about a significant transformation in European GMP regulations for the pharmaceutical industry. These revisions could enforce tighter controls and redefine standards, setting the stage for a new era in GMP compliance.

In response to these changes, pharmaceutical companies will need to review their documentation processes and platforms and reevaluate and validate their legacy systems (such as quality control, laboratory information management systems, or commercial off-the-shelf applications) to ensure compliance with the updated traceability and audit trail requirements. Overall, organizations will need to plan for system lifecycle governance and supplier management. If activities are outsourced, they must ensure regulatory accountability remains in-house. Additionally, companies deploying AI technologies in a GMP environment will need to develop robust internal capabilities to ensure data science governance and validate AI models (3).

The pharmaceutical industry must act swiftly to align with the evolving regulatory expectations. The stakeholder consultation closes on October 7, 2025, so there is still time to submit opinions on the three documents that will shape the future of GMP in Europe (7–9).

The 3-Year Work Plan for the Inspectors Working Group 2025-2027

Stakeholders’ Consultation on EudraLex Volume 4 - Good Manufacturing Practice Guidelines: Chapter 4, Annex 11 and New Annex 22. 

Preparing for EMA's 20226 Good Manufacturing Practice (GMP) Revisions: Chapter 4, Annex 11 & Annex 22.

Cheryl Barton is founder and director of PharmaVision, Pharmavision.co.uk.

The European Medicines Agency's 2025-2027 work plan for the Good Manufacturing and Distribution Practice Inspectors Working Group focuses on supply chain integrity, product quality, and the impact of new manufacturing technologies. Key revisions include updates to GMP guidelines, emphasizing documentation, digital system validation, and AI use in manufacturing. The revised guidelines will require pharmaceutical companies to reassess documentation processes, validate legacy systems, and ensure compliance with new standards. The industry must adapt quickly to these changes, with stakeholder consultation open until October 7, 2025.

The deadline for stakeholder consultation submissions on the new and updated regulations is Oct. 7, 2025. 

Stakeholders’ Consultation on GMP Annex 11, Chapter 4, and New Annex 22 

The European Medicines Agency (EMA) is encouraging the use of new approach methodologies (NAMs) as an alternative to animal testing in the assessment of safety and efficacy of new medicines during non-clinical development (1). In the European Union (plus Norway), 8.48 million uses of animals for scientific purposes occurred in 2022 (2). In most countries, the use of animals for some safety tests is required. For instance, 

 requires marketing authorisation holders to integrate the 3Rs (replacement, reduction, refinement) and welfare standards for the treatment of animals in all aspects of the development, manufacture, and testing of medicines (3). In October 2023, EMA published a concept paper on the revision of the guideline on the principles of regulatory acceptance of 3Rs testing approaches (4). Such alternative methods as NAMs can be highly effective at modelling individual aspects of safety and efficacy and should help to reduce and/or replace animal testing in line with the 3Rs principles (5). These principles include:

Availability of a defined test methodology (protocol, endpoints)

Description of the proposed NAM context of use (i.e., the circumstances in which the NAM is applied in the development and assessment of human or veterinary medicinal products)

Establishment of the relevance within that particular context of use

Demonstration of NAM reliability and robustness (5).

NAMs will need to be phased in. EMA is working with NAM developers to facilitate regulatory acceptance of these methodologies through briefing meetings and discussions with its Scientific Advice Working Party. Companies can also apply for the Committee for Medical Products for Human Use qualification of NAMs and voluntarily submit data generated from NAMs to the EMA; however, these data can be excluded from the regulatory decision-making process (

 Regulatory interactions between the European Medicines Agency (EMA) and new approach methodologies (NAM) developers. CVMP is Committee for Veterinary Medicinal Products.

The European Federation of Pharmaceutical Industries and Associations (EFPIA) endorses EMA's actions and believes it is feasible to phase out animal testing, “providing there is cross-sector collaboration, robust funding and incentives, global harmonization and streamlined regulatory acceptance of nan-animal methods” (6). In June 2025, EFPIA published pharma-specific recommendations regarding the phasing out of animal testing for chemical safety assessment. These include:

Strengthen collaboration between industry, regulators, academia, and non-government organisations (NGOs) through targeted consortia and incentives that catalyse NAM development.

Improve data sharing by creating safe harbour mechanisms, secure databases, and fee waivers for exploring novel methods.

Update regulatory frameworks to recognise the “last resort” principle, incorporate flexible qualification pathways, and align the roadmap with ongoing legislative revisions.

Institutionalise regular guideline reviews (e.g., every three years) to continuously phase out legacy animal tests and accelerate acceptance of new methods.

Build public trust by raising awareness of cutting-edge, non-animal approaches that can yield superior, more human-relevant safety data (6).

NAMs encompass a range of techniques, such as high-throughput screening, 

 modelling, often utilizing artificial intelligence and machine learning. NAMs focus on identifying changes in biological function that occur before outward symptoms, allowing for a more mechanistic understanding of the biomolecular interactions along the pathway toward harm (7). For instance, adverse outcome pathways (AOPs) enable tiered testing at multiple biological levels, increasing the overall predictive power and providing more accurate evidence-based approaches for hazard and risk assessment (

). AOPs could potentially reduce the levels of drug attrition rates resulting from undesired effects later in product development (8–10).

Furthermore, some organoids, organ-on-a-chip (OOC) technologies, and multi-organ microphysiological systems can simulate native organ structure and function, providing a cost-effective and accurate model for pharmacokinetics, pharmacodynamics, and toxicity studies (11). OOCs allow the rapid screening of multiple drug development candidates on a single chip, improving regulatory safety assessments and reducing the number of animal-based screens (12). In addition, several 

 cell biotransformation assays (CTAs) can assess carcinogenicity and exhibit good correlation with rodent bioassays. The CTAs can detect genotoxic and non-genotoxic carcinogens and provide a quick and more cost-effective alternative to 

 carcinogen models (13). Large pharma companies, such as AstraZeneca, GSK, and Pfizer, have established partnerships with OOC and CTA companies to harness this technology in their preclinical drug development programmes (14–16).

There is a paradigm shift toward a more mechanistically driven approach to toxicity testing for safety assessment. During the past decade, significant progress has been made in the development and evaluation of AOPs, OOCs, and 

 modelling technologies that enable risk-free biomedical testing and reduce the need for animal-based models (2). Stakeholders will need to work together to phase in NAMs and phase out animal testing (6). The regulators are keen to embrace new methodologies that replace, reduce, or refine the use of animals in research and encourage NAM developers to share their data and knowledge to facilitate the regulatory acceptance of these methodologies and ensure the NAMs are scientifically sound and useful in regulatory decision-making for the future (1).

Regulatory Acceptance of New Approach Methodologies: How to Interact with EMA

Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes Text with EEA Relevance

Concept Paper on the Revision of the Guideline on the Principles of Regulatory Acceptance of 3Rs (Replacement, Reduction, Refinement) Testing Approaches

Guideline on the Principles of Regulatory Acceptance of 3Rs (Replacement, Reduction, Refinement) Testing Approaches.

EFPIA Recommendations on Phasing Out Animal Testing for Chemical Safety Assessments.

Adverse Outcome Pathway Networks as the Basis for the Development of New Approach Methodologies: Liver Toxicity as a Case Study.

Pathways-Based Approach Across the Biosciences–Toward Application in Practice

Adverse Outcome Pathways Can Drive Non-Animal Approaches for Safety Assessment

Organoids and Organs-on-Chips: Recent Advances, Applications in Drug Development, and Regulatory Challenges

Liver-on-a-Chip: Considerations, Advances, and Beyond

Cell Transformation Assays for Prediction of Carcinogenic Potential: State of the Science and Future Research Needs.,

Medera’s Novoheart Releases Latest Cardiac Screening Innovation, CTScreen v1.5 to Advance High-Throughput, Automated Human-Based Drug Testing

GEN. Engineered Heart-on-a-Chip Replicates Drug Responses Found in Adult Humans. 8 Aug. 2019.

Scientists Mimic Human Organs on Microscopic ‘Chips’ That Enable Drug Testing

The European Medicines Agency (EMA) is promoting new approach methodologies (NAMs) to reduce animal testing in drug development, aligning with the 3Rs principles of replacement, reduction, and refinement. NAMs, including high-throughput screening, in vitro assays, and in silico modeling, offer mechanistic insights into drug safety and efficacy. The European Federation of Pharmaceutical Industries and Associations (EFPIA) supports phasing out animal testing through collaboration, funding, and regulatory updates. Techniques like organ-on-a-chip and cell transformation assays are advancing, providing cost-effective, human-relevant models for pharmacokinetics and toxicity studies.

EMA is phasing out animal testing and is asking pharmaceutical companies to use new approach methodologies.

EMA Encourages Use of New Approach Methodologies to Reduce Animal Testing 

The mRNA or messenger Ribonucleic Acid white text for medical or outbreak concept 3d rendering | Image Credit: ©niphon - adobe.stock.com

During the past decade, messenger RNA (mRNA)-based therapeutics have shown great promise in immunotherapy (e.g., cancer and vaccines), and non-immunogenic applications (e.g., protein replacement/supplementation therapy, regenerative medicine therapy, and genetic editing) (1). Several types of mRNA-based vaccines have emerged, namely non-replicating linear mRNAs (NRM), self-amplifying mRNAs (saRNAs), and circular mRNAs (circRNAs). Each mRNA type offers advantages and disadvantages (

 Types of messenger RNA (mRNA)-based vaccines. LNP is lipid nanoparticle.

Technological advances in the design and delivery of mRNA have catalysed the rapid development of mRNA COVID-19 vaccines by Pfizer-BioNTech and Moderna Therapeutics (3–4). Now, mRNA vaccines can be quickly created against different antigenic targets by changing the mRNA sequence, and companies are looking beyond COVID-19 at other infectious diseases, including Epstein-Barr virus, influenza, and Zika 

 In May 2024, the US Food and Drug Administration (FDA) approved Moderna’s next-generation base-modified mRNA-lipid nanoparticle (LNP) respiratory syncytial virus (RSV) vaccine mRESVIA (mRNA-1345) in adults aged 60 years and older with lower respiratory tract disease (5).

 Immunogenic messenger RNA (mRNA) vaccines and therapies in development.

In addition, manufacturers have begun to evaluate next-generation vaccine modalities in cancer (6). Although therapeutic mRNA-based cancer vaccines have yet to be approved, encouraging results have been reported by CureVac with CVGBM, its LNP-SAM mRNA vaccine CV0905010 in Phase I for glioblastoma (7). Some companies are combining mRNA vaccines with programmed cell death protein 1 (PD-1) inhibitors to activate the immune system and elicit tumour-specific T-cell responses. These include BioNTech/Regeneron with BNT111 plus Libtayo (cemiplimab) for patients with melanoma and Merck & Co./Moderna with LNP-delivered mRNA-4157/V940 in combination with Keytruda (pembrolizumab) also for melanoma (8–9).

Historically, production costs for mRNA therapies have been high, stability has been poor, and products have been associated with high immunogenicity. However, new strategies in mRNA modification, purification, and sequence design have led to the development of next-generation mRNA-based therapies 

In 2018, following decades of research and development, the first RNA-based therapy, Onpattro (patisiran), from Alnylam Pharmaceuticals reached the market (10). The LNP-encapsulated small interfering RNA (siRNA) was approved by FDA for the treatment of hereditary transthyretin amyloidosis (ATTR), and this opened the door for mRNA-based drugs in many applications. Numerous mRNA technologies are currently under evaluation at various stages of drug development, including Intellia Therapeutics NTLA-2001, an 

 gene-editing clustered regularly interspaced short palindromic repeats (CRISPR) agent and associated Cas9 endonuclease (CRISPR-Cas9) therapy that uses an mRNA-LNP system to inactivate the TTR gene to treat ATTR amyloidosis (11).

 Non-immunogenic mRNA therapies in development.

European biotech is leading the field in mRNA technologies

Several European biotech companies are leading the field in mRNA technology, including BioNTech, CureVac, eTheRNA, and Ethris. These companies compete with innovative biotech companies in the United States, such as ADARx Pharmaceuticals, Dicerna Pharmaceuticals, Greenlight Biosciences, Orna Therapeutics, Regulus Therapeutics, and Sirnaomics, as well as Abogen Biosciences and Stemirna Therapeutics in Asia.

. German biotech, BioNTech, is developing next-generation personalised therapies, focusing on oncology, cerebral diseases, and COVID-19 vaccines. It co-developed Comirnaty, the COVID-19 vaccine in partnership with Pfizer, and is gearing up for the commercial launch of its variant-adapted COVID-19 vaccine for the 2025/2026 season, pending regulatory approval. It is also developing BNT165e, an RNA-based vaccine for the prevention of 

 However, FDA has placed the Phase I/II trial on hold, and BioNTech is taking actions to address FDA’s requests and will work with the agency to assess the next steps.

In oncology, the company is leveraging its proprietary cancer vaccine platforms FixVac and iNeST to tailor treatment, and its RiboMab, RiboCytokine, and intratumoural immunotherapy platforms to target tumours directly. It is currently developing multivalent mRNA cancer Immunotherapeutics, which include BNT111 (Phase II, advanced melanoma), BNT113 (Phase II, metastatic head and neck cancer), BNT116 (Phase II metastatic NSCLC), BNT142 (Phase I/II, multiple solid tumours), and combination therapies, such as mRNA-based cancer immunotherapies for the early, adjuvant setting, and an anti-PDL1/ vascular endothelial growth factor A (VEGF-A) bispecific antibody candidate BNT327/PM8002 for the treatment of advanced solid tumours.

The company is developing modified RNA that includes methyl-pseudouridine modifications, nucleoside modifications, saRNAs, and trans-amplifying mRNA, with an improved immunogenetic profile. It is also developing novel delivery formulations to improve the targeted delivery of mRNA; these include lipoplex, LNPs, and polyplexes (12).

BioNTech has collaborations with Bayer, Genentech, Genevant, Fosun Pharma, Pfizer, and Regeneron. In February 2025, BioNTech completed the acquisition of Biotheus to obtain full global rights to BNT327 and all other pipeline candidates for US$800 million, plus additional performance-based payments of up to US$150 million (12). It signed a $1.5 billion strategic partnership in June 2025 with Bristol Myers Squibb to co-develop and co-commercialize next-generation bispecific antibody BNT327 targeted to PDL1 and VEGF-A for multiple solid tumours (13).

 German biopharmaceutical company CureVac N.V. was founded in 2000 and specialises in the development of mRNA-based vaccines and therapeutics. CureVac leverages its proprietary mRNA technology, with advanced omics and computational tools, to design and develop off-the-shelf and personalised precision immunotherapies to treat cancer (14). The company has been issued more than 1000 patents and is currently involved in patent litigation with BioNTech regarding the application of poly-A tail technology in mRNA constructs (15). In the US, seven patents are being assessed, and the trial is expected to start in September 2025.

CureVac has a broad product portfolio, which includes CVGBM, an off-the-shelf precision immunotherapy in Phase I for glioblastoma, and CVHNLC, a multiepitope mRNA-based precision immunotherapy in Phase I for squamous non-small cell lung cancer. It is also developing prophylactic vaccines for urinary tract infections and influenza/COVID-19, the latter being co-developed by GlaxoSmithKline (14).

The company has established collaborations with myNEO Therapeutics and MD Anderson Cancer Center in the oncology field, CRISPR Therapeutics on the development of gene-based medicines, and Acuitas Therapeutics to develop novel LNP delivery systems and LNP-formulated mRNA candidates. In February 2023, CureVac closed a US$250 million public offering and has a strong cash position to continue the development of its promising pipeline (14, 16).

. Belgium-based eTheRNA was founded in 2013 and developed mRNA and LNP technologies. In 2022, the company raised €39 million in a series B round that included the participation of Chien and Dekkers, co-founders of Dropshot Therapeutics. The company’s lead programme is a triple combination mRNA cancer vaccine that targets cytokines IL-21 and IL-7 and the membrane-bound co-stimulator 4-1BBL, which has shown promising results in triple-negative breast cancer (17). The LNPs provide targeted delivery of the mRNA directly to tumours, resulting in strong immune activation, tumour elimination, and durable immunological responses.

In January 2025, eTheRNA established a collaboration with Dropshot Therapeutics to develop RNA-based therapeutics for multiple new drug candidates across several indications in cardiac and renal diseases. The company will receive up to US$950 million, which includes an upfront payment plus milestone payments and tiered royalties following product launch (18). eTheRNA is working with Hasselt University on autoimmune mRNA therapeutics and Almirall on a multi-target alliance in medical dermatology (19–20).

Ethris GmbH was founded in Germany in 2009 and is a clinical-stage biotechnology company developing next-generation RNA therapeutics and vaccines based on non-immunogenic messenger RNA (SNIM RNA) and lipidoid nanoparticle (SNaPL). Its lead candidate, ETH47, is a broad-spectrum antiviral with a virus and mutation-independent mechanism, encoding interferon lambda. The product uses the SNaPL technology for inhalation or intranasal delivery and can be combined with existing antivirals to improve clinical outcomes in respiratory diseases such as uncontrolled asthma. In May 2025, the company was awarded a €10 million EU4Health Grant to support clinical development and expand antiviral applications of ETH47 and US$5 million from Coalition for Epidemic Preparedness Innovations (CEPI) and US$5 million from the Gates Foundation to develop its next-generation RNA therapeutics and vaccines (21–23). Etheris has collaborations with Lonza to develop spray-dried mRNA vaccines for respiratory diseases and HEQET Therapeutics to develop RNA-based therapeutics for heart attack and heart failure (24-25).

The future of mRNA vaccines and therapies

The global mRNA therapeutics and vaccines market is estimated at US$64.5 billion in 2024 and is forcasted to reach US$71.7 billion by 2034, exhibiting a compound average growth rate of 1.2% during 2025–2034 (26). The market will be driven by the rising incidence of chronic diseases and increasing awareness of the widespread potential of mRNA technology, the emergence of next-generation immunotherapy and non-immunotherapy drugs, and vaccines. Leading pharma and biotech companies, such as AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Moderna, Pfizer, Sangamo Therapeutics, and Sanofi, have made significant investments in this field, and numerous mRNA therapies and vaccines have entered clinical development (27).

To date, mRNA-based products have demonstrated great potential in combating a broad range of diseases either as monotherapies or in combination with approved agents. mRNA technology is constantly evolving, and the next-generation circRNA and saRNAs are likely to supersede mRNA linear formats in vaccine development due to increased immunogenicity and durability. However, the successful implementation of these next-generation products will rely on the development of targeted delivery vehicles and may also require additional modification to the mRNA molecule to improve safety and efficacy.

Progress and Prospects of mRNA-based Drugs in Pre-clinical and Clinical Applications

Current Landscape of mRNA Technologies and Delivery Systems for New Modality Therapeutics. 

Pfizer’s COVID-19 Vaccine Secures First Full FDA Approval.

Moderna Receives Full U.S. FDA Approval for COVID-19 Vaccine Spikevax.

Mullard, A. FDA Approves mRNA-based RSV Vaccine. 

Dolgin, E. Personalized Cancer Vaccines Pass First Major Clinical Test. 

CureVac’s CVGBM Cancer Vaccine Induces Promising Immune Responses in Phase 1 Study in Glioblastoma Presented at the ESMO 2024 Congress

BNT111/Cemiplimab Combo Significantly Improves ORR in Unresectable Melanoma

Moderna & Merck Announce 3-Year Data For mRNA-4157 (V940) in Combination With KEYTRUDA(R) (pembrolizumab) Demonstrated Sustained Improvement in Recurrence-Free Survival & Distant Metastasis-Free Survival Versus KEYTRUDA in Patients With High-Risk Stage III/IV Melanoma Following Complete Resection

Alnylam Pharmaceuticals Press Release | Aug 10, 2018 | Alnylam Announces First-Ever FDA Approval of an RNAi Therapeutic, ONPATTRO™ (patisiran) for the Treatment of Hereditary Transthyretin-Mediated Amyloidosis in Adults

Intellia Therapeutics Announces First Patient Dosed in the Phase 3 MAGNITUDE Study of NTLA-2001 as a Single-Dose CRISPR-Based Treatment for Transthyretin Amyloidosis with Cardiomyopathy.

BioNTech Announces First Quarter 2025 Financial Results and Corporate Update | BioNTech

BioNTech and Bristol Myers Squibb Announce Global Strategic Partnership to Co-Develop and Co-Commercialize Next-generation Bispecific Antibody Candidate BNT327 Broadly for Multiple Solid Tumor Types.

CureVac Announces Financial Results for the Fourth Quarter and Full-Year 2024 and Provides Business Update.

CureVac Receives Additional Positive Validity Decision from European Patent Office in Ongoing Litigation Against BioNTech SE

CureVac Announces Closing of $250 million Follow-on Public Offering of Common Shares

The Discovery of mRNA Therapy that Eradicates Tumours in Preclinical Trials

Strategic Multi-target Collaboration with Dropshot Therapeutics.

Etherna and Hasselt University Announce Autoimmune mRNA Therapeutics Research Collaboration

Almirall and Etherna Enter into a Multi-target Alliance to Develop mRNA-based Therapies in Medical Dermatology.,

$5M CEPI Grant for Spray-dried Mucosal Vaccines.

mRNA Vaccines and Therapeutics Market Report and Forecast 2025-2034.

Top 8 mRNA Vaccines and Therapeutics Companies

mRNA technologies offer great promise in immunotherapy and non-immunogenic applications.

Looking Beyond mRNA-based COVID-19 Vaccines to Innovative Therapeutics

On 14 Apr. 2025, the European Medicines Agency (EMA) published strategic recommendations designed to strengthen the supply chain of radiopharmaceuticals (1). In the recommendations, the Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG) highlighted key areas of vulnerability and proposed measures to mitigate the impact of shortages in the European Union (EU).

Radiopharmaceuticals are specialised drugs that contain radioactive isotopes and are used primarily in nuclear medicine. The production and distribution of radiopharmaceuticals involves several critical processes that must adhere to stringent regulatory guidelines to ensure the safety and efficacy of these products (2). As of 2024, all radiopharmaceutical products are considered medicines in the EU, and industrially prepared products must be authorized as pharmaceuticals (3). However, country-level regulation is diverse, and the different regulatory and Health Technology Assessment (HTA) systems have led to significant differences in the use and availability of radiopharmaceuticals across the EU (4–5).

Demand for radiopharmaceuticals increasing

Radiopharmaceuticals play important roles in medical imaging, diagnosis, and treatment. Several radiopharmaceuticals have received regulatory approval for therapeutic use, and many more are in clinical development (

EMA has published recommendations to address potential radiopharmaceutical shortages.