Cheryl Barton is director of PharmaVision, 

Cheryl Barton

Human head shape made from a large grid of pins connected with string. Communication technology and mental health concept | Image Credit: © ink drop - Stock.adobe.com

Over the past decade, researchers have developed a greater understanding of the relative contributions of the environment, genetic, and epigenetic influences on the onset and progression of Parkinson’s disease (PD). New strategies have emerged that seek to modulate inflammatory cellular mediators, mitochondrial function, and/or halt the accumulation of synuclein and neuromelanin (1–3).

In August 2024, German-based Centogene NV released new data from the landmark Rostock International Parkinson’s Disease (ROPAD) Consortium Study which aimed to characterize the genetics of PD to better understand disease progression, diagnosis, and treatment for patients (4). The study identified that approximately 15% of 12,580 patients studied harboured genetic variants that present new opportunities for genetic testing and the development of innovative therapies such as cell and gene therapies (CGTs) (5).

New formulations and novel non-biological drugs

More than 10 million people worldwide are living with PD, and it is now classed as the fastest-growing neurological condition in the world (6,7). Several companies such as NeuroDerm (a Tanabe Pharma company), Cerevel (an AbbVie company), and Swiss-based Contera Pharma A/S are working on non-biological agents with immediate or long-duration action to improve the symptoms of PD (8–10) (

). In October 2024, the US Food and Drug Administration (FDA) finally approved AbbVie’s Vyalev (foscarbidopa and foslevodopa), the first 24-hour infusion of levodopa-based therapy for motor fluctuations in adults with advanced PD (11). This single infusion helps reduce the pill burden whereby PD patients may take more than 20 tablets a day to control their symptoms. AbbVie gained approval for the drug, under the trade name Produodopa, from the European Commission (EC) in January 2024 (12). In May 2024, Portuguese BIAL Holding S/A launched a novel sublingual film formulation Kynmobi (apomorphine hydrochloride) in Germany, for the intermittent treatment of off episodes in adult patients with PD who are not sufficiently controlled by oral anti-Parkinson medication (13).

Pharma companies are actively pursuing the development of drugs that target novel pathways involved in the underlying mechanism of PD (

). These include BIAL’s BIA 28-6156, a small-molecule activator of glucocerebrosidase (GCase), a lysosomal enzyme involved in the breakdown of glycosphingolipids and UK-based Neurolixis’ NLX-112 (befiradol), a novel 5-HTA1A receptor agonist that has completed a Phase IIa proof-of-concept trial for dyskinesia in PD (14–16).

Innovative non-biological drugs under clinical development for Parkinson’s disease (PD).

Innovative biological therapies are progressing through trials

Several companies are looking to harness biologics to halt the accumulation of detrimental proteins such as alpha-synuclein (a-syn), which has been implicated in the pathology of PD (

). US-based AC Immune is evaluating ACI-7104 in Phase II, a monoclonal antibody (mAb) that has been shown to inhibit the accumulation of a-syn aggregates in preclinical animal models and the brain tissue of PD patients (17). An alternative approach is the use of adeno-associated virus (AVV) vectors to deliver genes that selectively modulate the production of proteins such as glutamic acid decarboxylase (GAD) to increase gamma-aminobutyric acid (GABA) levels, or glial cell line-derived neurotrophic factor (GDNF) to boost dopamine levels. In January 2024, Asklepios BioPharmaceuticals (AskBio, a subsidiary of Bayer AG) released positive data with its AAV2-GDNF showing that the one-time bilateral delivery of AB-1005 gene therapy was well-tolerated, and no serious adverse events (AEs) were observed (18). In October 2024, US-based MeiraGTx Holdings released positive top-line data from its clinical bridging study with MGT-GAD-025, an AAV-GAD, resulted in a significant and clinically meaningful improvement in Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) from baseline to Week 26 in patients with idiopathic PD (IPD) (19).

Cell and gene therapies under clinical development for the treatment of Parkinson’s disease (PD).

Cell-based therapy is expected to provide an alternative route to treat PD through the surgical injection of autologous induced pluripotent stem cell (iPSC)-derived dopamine neurons into the putamen, the brain region affected in PD. Denmark/China-based iRegene is evaluating chemically induced human dopaminergic neuron precursors derived from iPSCs to treat moderate to severe PD; the company entered clinical development with its gene therapy NouvNeu001 in the second half of 2023 (20). Similarly, Massachusetts-based BlueRock Therapeutics (a subsidiary of Bayer AG) has released promising Phase I follow-up data from its safety trial with its cell-based therapy bemdaneprocel (MSK-DA01) (21). Alternatively, Australia-based Living Cell Technologies (LCT) is developing an alginate-coated capsule containing clusters of neonatal porcine choroid plexus cells that contains a range of factors that support nerve cell functions and protective enzymes that are crucial for nerve growth and healthy functioning in PD patients (22).

Since 2019, the number of active clinical trials for PD has remained relatively consistent, with more than 136 trials per year. However, the proportion of disease-modifying to symptomatic therapies has been increasing during the past five years, and the diversity of drug targets across both symptomatic and disease-modifying drugs has also increased. Interestingly, the number of trials investigating drugs aiming to improve non-motor symptoms has expanded and several drugs are now being developed to target inflammation, a key driver of PD progression (23). But despite these significant advances, many drugs still fail to transition from Phase II to Phase III.

National and international organizations and foundations, such as Cure Parkinson’s, the American and European Parkinson’s Disease Association, Michael J. Fox Foundation, National Parkinson’s Foundation, and Parkinson’s UK, have an important role in raising awareness, supporting patients, and funding PD research. Pharma companies including Bayer, Biogen, Genzyme, GlaxoSmithKline, Sanofi, and Pfizer have made multi-million-dollar strategic investment investments, and several life-changing therapies, including CGTs, are steadily progressing through the clinic. If successful, these therapies could help rewire the PD brain circuits and fundamentally change the way patients are treated over the next decade (24).

1. Elsworth, J.D. Parkinson’s Disease Treatment: Past, Present, and Future. 

 May;127(5):785-791.
2. Pajares. M.; Rojo, A.I.; Manda, G.; Boscá, L.; Cuadrado, A. Inflammation in Parkinson’s Disease: Mechanisms and Therapeutic Implications. 

 Jul 14;9(7):1687.
3. Abeliovich, A.; Hefti, F.; Sevigny, J. Gene Therapy for Parkinson‘s Disease Associated with GBA1 Mutations. 

 11(s2): S183-S188.
4. Westenberger, A.; Skrahina, V.; Usnich, T.; et al. Relevance of Genetic Testing in the Gene-targeted Trial Era: The Rostock Parkinson’s Disease study. 

. 147(8) 2652-2667.
5. Centogene. Introducing the ROPAD Consortium: Unlocking Real-world Genetic Insights to Accelerate Treatment Access for Parkinson’s Disease. Webinar. October 2024.
6. Parkinson’s Foundation. Statistics. 

 (accessed 30 Oct. 2024).
7. BBC News. New Parkinson’s Drug Produodopa to be Available on NHS. 16 Feb. 2024.
8. NeuroDerm Ltd. ND0612 (accessed 30 Oct. 2024).
9. Cerevel Therapeutics. Cerevel Therapeutics Announces Positive Topline Results for Tavapadon in Phase 3 Adjunctive Trial for People Living with Parkinson’s Disease | Cerevel Therapeutics. News Release. 18 Apr. 2024.
10. Contera Pharma A/S. Contera Pharma Reports Topline Results from its Phase IIb Clinical Trial ASTORIA, evaluating JM-010 for the Treatment of Parkinson’s Disease Dyskinesia. News Release. 21 May 2024.
11. AbbVie. U.S. FDA Approves VYALEV (foscarbidopa and foslevodopa) for Adults Living with Advanced Parkinson’s Disease. News Release. 17 Oct. 2024.
12. AbbVie. AbbVie Launches PRODUODOPA (foslevodopa/foscarbidopa) for People Living with Advanced Parkinson’s Disease in the European Union. News Release. 9 Jan. 2024.
13. Bial. Bial launches Kynmobi in Germany. News Release. 3 May 2024.
14. Bial. BIA 28-6156. 

. (accessed 30 Oct. 2024).
15. Cavion. Cavion to Present Results of Phase 2 Essential Tremor Clinical Trial in Platform Presentation at the American Academy of Neurology. News Release. 24 Apr. 2019.
16. Neurolixis. Successful NLX-112 Clinical Results were Discussed in an Interview with the Parkinson’s UK Foundation. 15 Jan. 2024.
17. AC Immune. ACI-7104: Updates on Clinical Progress. 2024.
18. AskBio. AskBio Phase Ib Trial of AB-1005 Gene Therapy in Patients with Parkinson’s Disease Meets Primary Endpoint. News Release. 4 Jan. 2024.
19. MeiraGTx. MeiraGTx Announces Positive Data from Randomized, Sham-controlled Clinical Bridging Study of AAV-GAD for the Treatment of Parkinson’s Disease. News Release 15 Oct. 2024.
20. Cai M.; Wei, J.; Ren, X.; et al. NouvNeu001, A Phase 1 Stage Chemically Induced Human Dopaminergic Progenitor Cell Therapy for the Treatment of Mid- to Late-stage Parkinson’s Disease. 2024 International Conference. Abstract Number 700.
21. BlueRock Therapeutics. BlueRock’s Phase I Study with Bemdaneprocel in Patients with Parkinson’s Disease Meets the Primary Endpoint. News Release. 28 Aug. 2023.
22. LCT. NTCELL. Accessed 30 Oct. 2024.
23. Cure Parkinson’s. Parkinson’s Drug Therapies in the Clinical Trial Pipeline: 2024 Update. News Release. August 2024.
24. Kingwell, K. Gene Therapy Zeroes in on Parkinson’s Disease Brain Circuits. 

Cheryl Barton is director of Pharmavision, info@pharmavision.co.uk.


Vol. 36, No. 10
November/December 2024
Pages: 16–18

When referring to this article, please cite it as Barton, C. European Biotechs Unlocking Parkinson’s Disease. 

Articles

Centogene NV and ROPAD consortium publish data from a landmark study identifying genetic variants that may respond to innovative cell and gene therapies.

European Biotechs Unlocking Parkinson’s Disease

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

On 15 Oct. 2024, the European Federation of Pharmaceutical Industries and Associations (EFPIA) published an article to raise industry awareness that the European Union (EU) is developing a roadmap to advance precision oncology at the country level to address the growing burden of cancer in Europe (1). Cancer remains the second biggest cause of death in Europe. In 2024, the predicted mortality cancer rates are forecast to fall by 6.5% in men and by 4.3% in women in the EU (based on data from the five most populous countries and the United Kingdom). However, the number of deaths is still rising, with a total of 1,270,800 predicted deaths in 2024 in the EU and 172,900 in the UK, due to population growth and ageing (2).

New therapies, along with advances in prevention, screening, radiotherapy, and surgery are helping to save lives, but further collaboration, and partnership are needed. The “#WeWontRest until we beat cancer” campaign is underway (3). On 13 Nov. 2024, the EFPIA Oncology Platform organized a stakeholder roundtable in Brussels to bring together EFPIA member companies—AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Ipsen, Johnson & Johnson, Lilly, Novartis, MSD, Menarini, Pfizer, Roche, Sanofi, Servier, and Takeda—to help define future legislative and policy directions to improve the provision of personalized treatment for cancer patients (4).

The event was hosted by the Committee of the Regions, with scientific support from the European Regional and Local Health Authorities (EUREGHA) and Cancer Patients Europe, and aims to bring together stakeholders—policymakers, regional health authorities, patient advocates, and healthcare providers—to explore the challenges to improve access to precision oncology to ensure optimal and timely treatment and overcome healthcare disparities across Europe.

The EU has been developing policies to move toward personalized medicine (PM) and has made significant investments starting in 2010. As of 2017, €3.2 billion was invested in PM research across the medical innovation cycle ‘from bench to bedside’ from the research framework programs FP7 and Horizon 2020 (5).

In 2021, the European Commission (EC) published its cancer plan for Europe outlining several goals to reverse the rising trend of cancer across the EU (

). Europe’s Beating Cancer Plan was the EU’s response to medical needs and aims to tackle the entire disease pathways from prevention, early detection, diagnosis, and treatment, as well as the quality of life of the cancer patients and survivors (6).

EU initiatives in precision medicine in Europe

Many EU initiatives are underway to advance precision medicine in Europe. On 11. Sept. 2024, the Thematic Network on Advancing Precision Medicine for Europe’s Cancer Patients with artificial intelligence (AI)-powered Imaging held a webinar led by the European Society of Radiology to discuss with health stakeholders how AI-powered cancer care can improve personalized treatment strategies and reduce the burden of cancer (7).

Meanwhile, the Digital Oncology Network for Europe (DigiONE) pilot is underway in Europe. An amount of €3 million has been allocated for technology investment in a proof-of-concept learning health system in a precision oncology platform that aims to identify optimal cancer treatments by learning from every patient, not just those in clinical trials, through privacy-preserving interrogation of their standardized routine electronic health records (8,9).

Roadmap for a European cancer data management and precision medicine infrastructure

Aside from the goals laid out in Europe’s Beating Cancer Plan stakeholders recognize that for European citizens to have access to innovative precision medicines there is a need to develop a gold-standard cancer data management system. This will rely on three key elements: adopting standardized data formats; ensuring robust data privacy; educating professionals about the infrastructure’s benefits and leveraging cutting-edge technologies to transform cancer care (10).

Further work is needed to refine the EU roadmap on precision oncology but significant steps have already been taken to put in place the framework to reverse the rising trend of cancer across the EU. Stakeholders should keep abreast of the situation and can access details of the advancing precision oncology agenda in the EU online, via the EFPIA (11).

1. EFPIA. Advancing the Precision Oncology Agenda in the EU: Developing a Roadmap at Country Level to Address the Growing Burden of Cancer in Europe. Guest Blog. 15 Oct. 2024.
2. Santucci, C.; Mignozzi, S.; Malvezzi, M.; et al. European Cancer Mortality Predictions for the Year 2024 with a Focus on Colorectal Cancer. 

35 (3) 308–316.
3. EFPIA. #WeWontRest Until We Beat Cancer. 

Accessed 22 Oct. 2024.
4. EFPIA. Advancing the Precision Oncology Agenda in the EU. Brussels, Belgium. 13. Nov. 2024.
5. Nimmesgern, E.; Norstedt, I.; Draghia-Akli, R. Enabling Personalized Medicine in Europe by the European Commission‘s Funding Activities. 

 14 (4) 355–365.
6. European Commission. 

. Communication Paper, 2021.
7. Nikolski, M.; Hovig, E.; Al-Shahrour, F.; et al. Roadmap for a European Cancer Data Management and Precision Medicine Infrastructure. 

5, 367–372.
8. Mahon, P.; Chatzitheofilou, I.; Dekker, A.; 

 A Federated Learning System for Precision Oncology in Europe: DigiONE. 

 30, 334–337.
9. Nahon. P. Building a Digital Oncology Network for Europe (DigiOne) The Digital Institute for Cancer Outcome Research (DigiCore). 

Accessed 22 Oct. 2024.
10. European Commission. Recording—EUHPP Live Webinar—How to Advance Precision Medicine for Europe’s Cancer Patients with AI-powered Imaging (11 September 2024). News Announcement, 11 Sep. 2024.
11. EFPIA. Advancing the Precision Oncology Agenda in the EU. 13 Nov. 2024


Vol. 36, No. 10
November/December 2024
Pages: 9–10

When referring to this article, please cite it as Barton, C. Advancing the Precision Oncology Agenda in Europe. 

The European Commission has developed a roadmap aimed at reversing the rising trend of cancer across the European Union. 

Advancing the Precision Oncology Agenda in Europe

cosmetic molecule and chromosome background | Image Credit: ©Thongden_studio - stock.adobe.com

Over the past century, life expectancy has dramatically increased in most parts of the world, but humans are spending more years in poor health than at any point in history (1). However, technological and scientific advances have increased our understanding of the ‘hallmarks of ageing’ resulting in molecular and cellular changes that lead to the modulation of mitochondrial dysfunction, inflammation, and cellular senescence (2).

This article was published in the October 2024 print issue of 

Ageing is emerging as a druggable condition with multiple pharmaceuticals able to alter the pace of ageing in model organisms. Anti-ageing activity has been demonstrated in some US Food and Drug Administration (FDA)-approved drugs such as the immunosuppressant rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, and the anti-diabetic agent, metformin, an AMP-activated protein kinase (AMPK) activator (3). US-based Aeovian Pharmaceuticals and Amplifier Therapeutics are looking to develop next-generation AMPK and mTOR inhibitors in age-related diseases (4,5).

Many biopharmaceutical companies are now prioritizing ageing research for early-stage discovery or therapeutic pipeline development. BioAge Labs, Fauna Bio, and Insilico Medicine are deploying artificial intelligence (AI)-enabled multi-omic platform technologies to identify novel anti-ageing targets. Several experimental drugs—dasatinib, fisetin, navitoclax, and quercetin—have demonstrated senolytic activity, and inhibitors targeting Bcl-2, HSP, tyrosine kinase or P53, are now being evaluated by biopharma as potential senolytics (6). One of the most advanced programmes is Unity Biotechnology’s UBX1325 (foselutoclax), a Bcl-2 inhibitor in Phase II development for the treatment of age-related macular degeneration (AMD) (7).

Several European start-ups are actively pursuing anti-ageing research including Swiss-based Vandria and UK-based clook.bio and Genflow Biosciences.

Vandria mitochondrial therapeutics look promising in neurodegenerative disease models

Vandria is developing novel mitophagy inducers that rejuvenate cells to treat age-related and chronic diseases. The decline in mitochondrial function has been implicated in many age-related diseases including mild cognitive impairment (MCI), neurodegenerative diseases, and muscular disorders. Vandria has demonstrated that removing damaged mitochondria via mitophagy can rejuvenate cells leading to an improvement in cellular functions and the generation of energy or ATP (adenosine triphosphate) (8).

 screening platform and generated a novel pipeline of small-molecule mitophagy inducers to target different tissues and address specific unmet medical conditions. Its lead programme, VNA-318, has completed investigational new drug (IND) studies for central nervous system (CNS) indications including MCI, Alzheimer’s, and Parkinson’s diseases, and other forms of dementia. Its other preclinical programmes include VNA-052 for sporadic inclusion body myositis, VNA-438 for Metabolic Dysfunction Associated Steatohepatitis (MASH), VNA-710 for idiopathic pulmonary fibrosis (IPF), and VNA-897 for an undisclosed target (9).

In February 2024, Vandria was awarded a CHF 2.5 million (US$2.8 million) research grant from the Swiss Innovation Agency Innosuisse to help advance the development of VNA-318 (10). The funds will be matched with CHF 4.6 million from the company initiative to progress VNA-318 into Phase I/IIb clinical trials in 2025. In preclinical animal models, VNA-318, has been shown to improve memory and learning. Additionally, VNA-318 has strong disease-modifying effects in Alzheimer’s and Parkinson’s disease models and has a wide safety window. The company has been issued a composition of matter patent by the US Patent Office covering VNA-318 and other compounds (10).

The company is also advancing the development of another mitophagy lead candidate, VNA-052, for muscle diseases. This clinical programme was awarded a research grant, totaling €1.1 million (US$1.2 million) from Eurostars, a programme co-funded by the European Union (10). In August 2024, Vandria announced the second closing of its Series A financing raising CHF 28.3 million (US$30.7 million). The funds will be used to support its clinical development programmes (11).

Pioneering gene therapies to decelerate the ageing process

Recent advances in gene editing and delivery have allowed scientists to partially reprogramme cells and reverse the effects of ageing (12). Two UK start-ups, clock.bio and Genflow Biosciences, are leveraging human inducible pluripotent stem cells (hiPSC) to prevent and treat age-related diseases:

 was founded in 2020, by Mark Kotter and has attracted more than US$4 million (€3.6 million) in funding (13). The company has developed an ageing model that force-ages hiPSCs to trigger self-rejuvenation. The company deploys unbiased clustered regularly interspaced short palindromic repeats (CRISPR) screens to identify gene candidates that are causally linked to cell rejuvenation. Clock.bio aims to decode the biology of human rejuvenation across the entire human genome and generate a comprehensive atlas of disease and rejuvenation targets for clinical translation (14).

 was founded in 2020 and has R&D facilities in Belgium. Its lead compound, GF-1002, a suspension of an adeno-associated virus vector-based (AAV-based) gene therapy that delivers the centenarian variant of the sirtuin 6 (SIRT6) gene, a gene intricately linked to cellular stress responses that can promote longevity in mice. GF-1002 has demonstrated promising preclinical results and is due to enter clinical development in 2025 for the treatment of MASH (15). In January 2024, Genflow established two technological innovation partnerships with Revatis SA and with EXO Biologics to develop advanced therapy medicinal products (ATMPs) in sarcopenia and Werner Syndrome, respectively (16). In April 2024, Genflow raised £715,000 (US$959,000) through the placing and subscription for new stock organized by Capital Plus Partners (17). Genflow has been awarded a European Patent with the University of Rochester, New York, for SIRT6 in the prevention and treatment of age-related diseases (18).

In the United States, numerous companies are also pursuing cellular reprogramming strategies including Altos Labs, Longeveron, Retro Biosciences, Rejuvenate Bio, and Turn Biotechnologies (19–23).

Great strides have been made in anti-ageing longevity research, numerous drug targets have been identified, and several agents are progressing steadily through the clinic. In 2021, venture capitalists invested $9.26 billion (€8.3 billion) in this area, with cellular reprogramming and rejuvenation attracting the most attention (24). Pharma has announced several partnerships in this space including Eli Lilly/Fauna Bio, Sanofi/Insilico Medicine, and Pfizer/VitaDAO. While US biotechs dominate the scene, European and UK start-ups are gaining traction, and there are significant opportunities for pharma to expand their foothold and take a more proactive approach in the treatment of chronic age-related diseases.

We’re Spending More Years in Poor Health than at Any Point in History. How Can We Change This?

Hallmarks of Aging: An Expanding Universe

Faragher, R. Anti-ageing Treatments: These Two Drug Types are Being Investigated. 

Aeovian Pharmaceutical doses first participants in Phase 1 Clinical Trial, Strengthens Leadership Team, and Raises Additional $50 million Financial

Amplifier Therapeutics. Amplifier Therapeutics, a Cambrian Bio Pipeline Company, Doses the First Patients in the Phase 1B Clinical Trial and Closes New Financing fromFuture Ventures and RA Capital Management. New Release, 17 Oct. 2023.

Senolytics: from Pharmacological Inhibitors to Immunotherapies, a Promising Future for Patients’ Treatment

Lobo, A. Parkinson’s Grant will Advance VNA-318 for Parkinson’s, Age-related Diseases. 

Hevolution Foundation and Dolby Family Ventures join Vandria’s 2nd Series A closing, bringing the total round to $30.7M (CHF 28.3M) to Progress the Mitophagy Inducer VNA-318 into CNS Clinical Development

Cellular Rejuvenation: Molecular Mechanisms and Potential Therapeutic Interventions for Diseases

Clock. bio Launches to Decode Rejuvenation Biology Across the Human Genome

A White Paper for Rejuvenation Therapies and Blueprint for Clock.bio

Secures Two Research Grants from Belgium’s New Technological Innovation Partnership

Genflow Biosciences Plc Successful Placing and Subscription To Raise £715,000, Grant of Warrants and PDMR Notifications

Genflow Biosciences Plc Announced the Publication of a Key European Patent in Partnership with the University of Rochester, New York

Altos Labs Launches with the Goal to Transform Medicine through Cellular Rejuvenation Programming

Longeveron Announces Second Quarter 2024 Financial Results and Provides Business Update

Rejuvenate Bio Announces New Preclinical Research Evaluating Cellular Reprogramming for Age Reversal

Turn Biotechnologies Reports Historic Skin Cell Rejuvenation Breakthroughs at ESDR this Week

Longevity Investment Hits 3.01 Billion in Full Year 2023

Cheryl Barton, PhD,is director of PharmaVision.


Vol. 36, No. 9
October 2024
Pages: 14–15, 18

When referring to this article, please cite it as Barton, C. European Biotech Targeting Anti-ageing. 

Novel mitophagy inducers and gene therapies that restore cellular function and decelerate the ageing process.

European Biotech Targeting Anti-ageing

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

On 5 Sept. 2024, the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) published high-level principles and recommendations for staff across the European Medicines Regulatory Network (EMRN) regarding the use of generative artificial intelligence (AI), namely large language models (LLMs) (1).

This article was published in the October 2024 issue of

LLMs are widely used by regulatory staff in various daily tasks including education and tutoring, language translation, search and summarizing information, writing assistance, and providing coding language support (2). However, the deployment of LLMs may result in variable results and inaccurate responses, and they can present potential data security risks in terms of confidential information, data protection, and privacy (2). Thus, the guidelines and principles lay the foundation for the safe and responsible use of LLMs so users “avoid pitfalls and risks” (1).

The EMA/HMA’s guiding principles aim to ensure users to do the following:

take appropriate measures to ensure safe input of data, apply critical thinking, and cross-check outputs continuously learn how to use LLMs effectively know who to consult when facing concerns and report issues (2). In addition, the organizational principles:

define governance that helps users have a safe and responsible use, specifying permitted use cases, providing training, and monitoring risks

Overall, the guiding principles provide a working framework to ensure LLMs are used safely and ethically and are effectively implemented in regulatory science and for medicines regulatory activities.

HMA-EMA multiannual AI workplan 2023-2028

The guiding principles represent one of the deliverables from the HMA/EMA 

 published in December 2023 (3). This workplan guides EMA and EMRN in their use of AI, maximizing the benefits while managing the risks and facilitating information sharing. The first version of the Multi-annual AI Workplan focuses on four critical dimensions—guidance, policy and product support; tools and technologies; collaboration and change management; and experimentation—and will be regularly updated under the oversight of the HMA-EMA Big Data Steering Group (BDSG) (3).

Over the coming months and years, EMA’s Committee for Medicinal Products for Human Use (CHMP) Methodology Working Party (MWP) will help to develop the 

document, which will include domain-specific guidance on pharmacovigilance and other areas. From mid-2024 work was initiated on preparations for the European Artificial Intelligence Act (AI Act), which came into force in August 2024, and an observatory will be created to monitor the impact of AI and the emergence of novel systems and approaches (3,4).

The EMRN will survey its capabilities to analyse data including the use of AI, and this survey will be used to inform collaborative efforts to enhance the analytics capability of the ERMN to ensure all parties are compliant with data protection legislation. In addition, a Network Tools policy will be published to help foster collaboration, integration, and reusability of tools and models within the EMRN (3).

The EMRN will continue to work with partners on AI on an international scale including the International Coalition of Medicines Regulatory Authorities and other agencies in the European Union, as well as with academia and the devices sector. Furthermore, the European Specialised Expert Community of the EMA MWP, will establish a Special Interest Area on AI to provide a forum for collaboration and knowledge sharing, and the EU-Network Training Centre will provide a framework and platform to upskill staff on AI and Data Analytics and support the development and delivery of BDSG Data Science Curriculum (3).

EMA and HRA recognize that AI is a rapidly moving field, and it is essential for regulatory personnel to be provided with a structured approach to integrate these tools in their daily tasks while safeguarding information and maintaining trust. EMA is leading by example and has promptly responded to the implementation of the AI Act, which aims to ensure that AI developed and used in the EU is trustworthy and that there are sufficient safeguards in place to protect people’s fundamental rights. Pharma should take heed as the AI ACT will impact all industries, and it will be essential that companies work closely with the AI Office and other relevant authorities to ensure the safe deployment of AI solutions that will be beneficial to society and drive future innovation in the European pharmaceutical industry (5).

Harnessing AI in Medicines Regulation: Use of Large Language Models (LLMs)

Guiding Principles on the Use of Large Language Models in Regulatory Science and for Medicines Regulatory Activities

Multi-Annual Artificial Intelligence Workplan 2023-2028: HMA-EMA Joint Big Data Steering Group

European Artificial Intelligence Act Comes into Force

Barton, C. European Artificial Intelligence Act Comes into Force. 

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

When referring to this article, please cite it as Barton, C. Responding to the Increased Use of Generative AI. 

Regulators, EMA and HMA, have published principles and recommendations 
on the use of LLMs, which are being increasingly used for daily tasks.


Responding to the Increased Use of Generative AI

On 1 Aug. 2024, the European Artificial Intelligence Act (AI Act) came into force (1). The AI Act is designed to ensure that artificial intelligence (AI) developed and used in the European Union (EU) is trustworthy, and that there are safeguards in place to protect people’s fundamental rights. In January 2024, the European Commission (EC) launched a package of measures to support European small and medium enterprises (SMEs) and start-ups in the development of trustworthy AI, and in May, the EC established an AI Office (2,3). In July 2024, the amended European High Performance Computing Joint Undertaking (EuroHPC JU) Regulation came into force to further develop, deploy, extend, and maintain the EU supercomputing and data infrastructure (4). This paved the way for the establishment of AI Factories, dedicated AI supercomputers, that can be used for training General Purpose AI (GPAI) models (5).

This article was published in the September 2024 issue of 

The AI Act aims to harmonize AI across the EU to encourage the uptake of this technology and support innovation and investment. The AI Act also prohibits certain AI practices and sets out regulations on “high-risk” AI systems and those that pose transparency risks (

Figure 1. Definition of artificial intelligence (AI)-based product safety and risk-based approach. (Figure courtesy of the author)

The AI Act also introduces rules to reduce the systemic risk of systemic GPAI models that are capable of performing a wide range of distinct tasks such as the generation of human-like text (6). The new legislation imposes stricter regulation and fines on tech companies operating generative AI models (i.e., DeepMind and OpenAI will fall under the general-use AI category and would be classed as minimal risk). However, developers of high-risk models would be asked to evaluate models, assess and mitigate systemic risks, conduct adversarial testing, report serious incidents to the EC, ensure cybersecurity, and report on their energy efficiency (6).

The European Federation of Pharmaceutical Industries and Associations (EFPIA) welcomes the AI Act and “believes in the potential of applying AI to deliver benefit for patients, life-science companies, and society” (7). However, it stresses that “the regulatory frameworks governing the use of AI in research, development, and manufacture must be fit-for-purpose, risk-based, non-duplicative, globally aligned, and adequately tailored” (7). When AI-enabled tools are used in pharma R&D, they are exempt from the requirements of the EU AI Act; however, developers and deployers of AI-enabled digital health tools (DHTs) and AI-enabled digital medicine would be impacted by the AI Act, but they would not be considered high risk (8).

Enforcement of the AI rules will be phased in

EU Member States have a year to designate national competent authorities to oversee the application of the AI rules. The Commission’s AI Office will oversee the implementation of the AI Act at the EU level, and be responsible for enforcing the rules for GPAI models (1).

The EC will establish the following three advisory bodies to support the implementation of the rules:

European Artificial Intelligence Board—

to ensure the uniform application of the AI Act across EU Member States and to cooperate between the EC and the Member States.

A scientific panel of independent experts—

to offer technical advice and input on enforcement. The panel can issue alerts to the AI Office about risks associated with GPAI models.

a diverse set of stakeholders to offer guidance to the AI Office (1).

The AI Office has the power to enforce these policies. Companies that do not comply with the rules will be fined 1.5–7% of their global annual turnover depending on the violation (e.g., companies can be fined up to 1.5% for supplying incorrect information) (1).

The AI Act’s regulations will take effect in phases. Rules regarding prohibited practices will apply as of 2 Feb. 2025; obligations on GPAI models will apply as of 2 Aug. 2025; and both transparency obligations and obligations on high-risk AI systems will apply as of 2 Aug. 2026 (9).

In the interim, the EC launched the AI Pact to encourage and support organizations before implementing the AI Act (10). The EC has urged the industry to voluntarily commit to the AI Act requirements before the legal deadline. In November 2023, it obtained responses from more than 550 organizations, and the AI Office initiated the development of the AI Pact, based upon two pillars:

establish a gateway to engage the AI Pact network, encourage the exchange of best practices, and provide practical information on the AI Act implementation process

encourage AI system providers and deployers to prepare early and take actions towards compliance with requirements and obligations set out in the legislation.

The AI Pact has enabled the EC to work with stakeholders to support them in understanding the objectives of the AI Act, to adapt and prepare for the implementation of the AI Act, and to share knowledge and build trust in AI technologies (10).

Meanwhile, the Joint Research Centre continues to undertake independent, evidence-based research to support EU policies and determine the societal impact of the AI Act across Europe.

The EU AI Act sends a clear message to the rest of the world that Europe is taking AI very seriously and emphasises the importance of trust, transparency, and accountability. The EC is the first governmental body to create a legal infrastructure on AI and has paved the way for others to emulate and replicate.During the coming months, rules will be phased in and European standards will be refined. Therefore, companies need to work closely with the AI Office and other relevant authorities to ensure the safe deployment of AI solutions that will be beneficial to society and drive future innovation in Europe.

Commission Launches AI Innovation Package to Support Artificial Intelligence Startups and SMEs

Commission Establishes AI Office to Strengthen EU Leadership in Safe and Trustworthy Artificial Intelligence

Setting Up of AI Factories is Now Possible after EuroHPC Regulation Amendment

The EU Passes the AI Act and its Implications for Digital Medicine Are Unclear

International Bar Association. The Regulation of Foundation Models in the EU AI Act. 

EFPIA Statement on the Use of AI in the Medicinal Product Lifecycle in the Context of the AI Act

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


Vol. 36, No. 8
September 2024
Pages: 9-10

When referring to this article, please cite it as Barton, C. European Artificial Intelligence Act Comes into Force. 

What impact will the AI Act have on pharma and digital medicine?

On 3 July 2024, the Health Committee of the Bundestag amended and approved the Federal Government’s Medical Research Act (Medizinforschungsgesetz or MFG) (1). The new legislation will impact national laws to simplify clinical trials and approval processes for drugs and medical devices. MFG will also amend rules on advanced therapy medical products (ATMPs) and drug pricing and reimbursement laws (Arzneimittelmarktneuordnungsgesetz [AMNOG]). In addition, the new legislation will result in a reorganization of the regulatory agencies (The Federal Institute for Drugs and Medical Devices [BfArM] and Paul Ehrlich Institute [PEI]) and ethics committees (2).

Pharma may choose confidential pricing … but at a cost

The MFG allows pharmaceutical companies confidential pricing, providing they have drug research departments in Germany that can demonstrate “relevant own projects and cooperation with public institutions in preclinical or clinical drug research in Germany” (3). For instance, if at least 5% of approved study subjects participate in clinical trials in Germany, then manufacturers could be exempt from the AMNOG guardrails that were introduced with the Statutory Health Insurance Finance Stabilization Act in November 2022 (4).

Once a pharma company has completed price negotiations with the National Association of Statutory Health Insurance Funds (GSK-SV), they will have five days to decide whether to keep the pricing of new patent-protected drugs confidential or transparent. Within seven days of receipt, the GSK-SV will decide whether ‘sufficient’ proof has been provided. If a pharmaceutical company requests confidential pricing, an additional discount of 9% will be imposed on the agreed sales price (not the pharmacy sales price) (3).

Companies that opt for confidentiality will also be obligated to reimburse the health insurance funds and other payors the overpaid difference between the ‘public’ and the ‘real’ price and will also have to reimburse the health insurance funds the overpaid portions of the mandatory surcharges for pharmacies and wholesalers and value-added tax (VAT) (3). Therefore, the final price negotiated by companies to keep drug prices secret could result in more than the 9% discount. The new rules for confidential reimbursement prices shall apply as of 1 Jan. 2025 and will be enforced until 28 June 2028 and reviewed in late 2026 (3).

Confidential pricing has proved a contentious issue among stakeholders in Europe. On one hand, the pharma industry in Europe has been keen to move towards confidential pricing because German reimbursement prices are regularly used as reference prices in other European countries, and an unfavourable price in Germany can have a significant impact on the price achieved in other European countries and abroad. In the past, this has led manufacturers to withdraw drugs from the German market; for instance, Bristol Myers Squibb decided not to launch the cancer drug Opdualag (nivolumab/relatlimab combination) in Germany, due to pricing pressures (5). If a company chooses to keep the reimbursement price confidential, it would not be listed in public sources or disclosed to pharmacies and could lead to differential pricing, the ‘public’ price, and the ‘real’ or agreed (discounted) price (3).

In 2022, the ‘AMNOG guardrails’ regulations were introduced to protect against excessive prices for patent-protected drugs with no or only a small or non-quantifiable benefit (6). These regulations will be deleted and replaced by the economic development goals laid out by the German Government in its new Pharma Strategy (6,7). However, the GSK-SV fears the lack of transparency could lead to increases in pharmaceutical expenditure (8,9). This is a major concern given that more than 73 million German citizens with statutory health insurance have already witnessed a significant increase in health insurance contributions earlier this year, and there is pressure on the Federal Ministry of Health to raise contributions further (6).

The new Pharma Strategy aims to make Germany more attractive to the pharma industry

The MFG is part of the German government’s National Pharma Strategy to strengthen Germany’s position as a business and pharmaceutical location (10). The Strategy Paper 4.0–Improving the General Conditions for the Pharmaceutical Sector in Germany lists several specific reform ideas all of which will have a significant impact on the pharmaceutical industry and aim to improve market access and pricing environment in Germany (Figure 1).

Figure 1: Strategy Paper 4.0 points of reform. Source: modified from (10). Figure courtesy of the author.

Germany is the fourth largest pharmaceutical market in the world and the largest European market generating €56.5 billion in 2022 and growing by 5.4% per annum (11). According to Marcus Schmidt, Germany Trade & Invest Director of Chemicals and Health, “The pharmaceutical strategy underlines the great importance of this sector for the federal government. Together with the laws that have already been introduced, Germany will expand its leading role in Europe in the areas of research and development as well as production” (10). Several pharma companies—Daiichi-Sankyo, Eil Lilly, and Sanofi—have all increased their investment in Germany in the past nine months (12).

The latest reform could have a significant impact on drug pricing and will link it more closely to local investment in clinical trials and R&D in Germany. However, the MFG will not come into force until it has received the seal of approval from the German Federal Council (Bundesrat), and this is unlikely to occur until the fourth quarter of 2024 (3).

 Entwurf eines Medizinforschungsgesetze Drucksache 20/11561. 29 May 2024.

Germany Amends Drug Pricing and Reimbursement Laws with the “Medical Research Act”–Drug Pricing Becomes Intertwined with Local Clinical Research Expectations.

 Blog. Insideeulifesciences.com. 12 July 2024.

Health Committee Approves Medical Research Act.

Simon-Kucher. Germany: How the GKV-FinStG Law is Transforming the Pharma P&R Landscape. Simon-kucher.com. 24 Feb. 2023.

Are German Drug Pricing Regulations Chasing Some Drug Makers Away, Causing Them To Not Launch Products In The Market?

Health Insurance Companies Should Support the Pharmaceutical Industry

German Government Pursues New Pharma Strategy with Significant Reform Ideas

. Blog. Covington. Insideeulifesciences.com. 21 Nov. 2024.

Secret Prices Make Care More Expensive Without Improving It

. GKV. GKV-spitzenverband.de. 6 June 2024.

What are the Implications of Confidential Rebates in Germany?

Big Changes Coming in German Health, Pharma, Pharmaceuticals

. Germany Trade and Invest, GTAI. gtai.de 14 Dec. 2023.

. Germany Trade and Invest, GTAI. gtai.de (accessed 12 July 2024).

Germany’s New Medical Research Act Will Allow Pharma Companies Confidentiality on Price

Cheryl Barton, PhD, is director of PharmaVision, info@pharmavision.co.uk.

®
Vol. 36, No. 7
July/August 2024
Pages: 9–10

When referring to this article, please cite it as Barton, C. Germany Amends and Approves the New Medical Research Act. 

Germany’s Medical Research Act allows pharmaceutical companies to keep drug prices confidential.