Will EU patients get the right treatment after legislation?

The EU’s proposal for a revision of the general pharmaceutical legislation aims to ensure EU citizens have access to affordable medicines and that unmet medical needs are addressed – all whilst ensuring Europe remains competitive, innovative, and sustainable. Yet, a leaked draft suggests the revision will not build a future based on Advanced Therapy Medicinal Products.

On the global stage, there are exciting new therapies being made available to people with debilitating, painful, and potentially life-threatening diseases, including rare conditions. In the UK, a life-saving gene therapy has been given for the first time by the NHS to a 19-month-old girl with a fatal disorder, metachromatic leukodystrophy (MLD). In the US, Victoria Gray was the first person with sickle cell disease to receive a CRISPR gene editing therapy via a clinical trial and has described how she went from being in constant pain to living a life where she can “thrive”. 

These successes are cause for celebration – not only for the individuals and families involved, but also for patient groups and the industry that develops therapies for rare diseases. The outcomes for European patients may be more precarious, however, if the European Commission’s new legislation does not strengthen some of the provisions currently contained in the leaked draft, such as for ‘hospital exemption’ licenses and the use of rules for genetically modified organisms being applied to ATMPs. 

The scale of rare diseases

The EU defines a condition as being ‘rare’ if it affects fewer than 5 people in 10,000. There are around 6,000 to 7,000 known rare diseases; approximately 80% are genetic, and of those, 70% begin in childhood. Rare diseases are thought to affect up to 36 million people in the EU. That is an enormous number of people to be directly affected and, when considering the ramifications for families, caregivers, and health systems, conditions deemed as rare have a significant impact on the wider society.

Transformative therapies

Advanced therapy medicinal products (ATMPs) are based on genes, cells, or tissues. They offer fresh hope for people living with rare diseases with no viable treatment options today and are also being developed to address chronic diseases affecting large patient populations, such as diabetes and heart disease.  

ATMPs are unique in their potential to durably treat or even cure devastating diseases. They are very different to traditional medicines – being small molecules or biologics – and they should be treated as such. ATMPs are revolutionising medicine and healthcare. Specialised centres across Europe are developing world-class expertise in managing patients to be treated with ATMPs, but also in working together with developers in R&D activities and the logistics of these complex treatments.

As scientific exploration progresses, there is more hope in developing therapeutic options that treat currently incurable diseases. But for these to become a realistic option, the ecosystem of investment, research, clinical trials, manufacturing, reimbursement, and pharmacovigilance should be adapted to fit with the innovative nature of these treatments. 

Legislators need to understand and appreciate the unique characteristics of ATMPs and be willing to adopt new tailored policies, rather than relying on the systems of the past that were created for conventional medicines. Organisations such as ARM work closely with key stakeholders – including policymakers – to raise awareness about the potential of these treatments to alleviate suffering among patients and reduce the strain on healthcare systems.  

Special dispensations via the hospital exemption

Following the adoption of the EU’s ATMP regulation, European health systems have been able to offer novel treatments to patients with unmet needs via the ‘hospital exemption’ (HE) scheme.  This has been a useful pathway to enable patients with a high unmet medical need to receive an ATMP under controlled conditions where no approved therapy is available. Such products would be produced by clinicians and given to individual patients in a hospital setting. 

However, the application of HE in the EU varies significantly across member states, depending on a country's position when choosing between robust regulatory standards and treatment affordability. The different levels of implementation have led to a situation in which HE is used in a broader set of situations and in different ways than initially intended. 

If improperly used, HE has the potential to seriously undermine the world-class regulatory standards of the European Medicines Agency. For a product to receive market authorisation, it must meet a high level of requirements to provide consistent product quality, efficacy, and safety. While HE is subject to approval and licensing by regulatory authorities in member states, the review process varies widely across Europe. In some countries, clinical data is required to use the experimental product, while in others an HE license can be granted in the absence of clinical data. The gaps in evidence requirements for granting an HE license open the possibility that patients are exposed to products where the quality and safety have not been fully assessed.

In April 2020, the EMA issued a warning against the use of unproven cell therapies, highlighting that some patients who have been given unproven or unregulated cell-based therapies have suffered serious, sometimes fatal, side effects, including infections, unwanted immune reactions, tumour formation, loss of vision, and bleeding in the brain.

In a scenario where ad hoc treatments can sidestep official marketing authorisation routes, this can also have an impact on EU-based ATMP developers by dis-incentivising them from investing in the pursuit of new therapies. 

Although the leaked draft introduces more stringent data collection requirements for the use of ATMPs under the HE, it does not go far enough in ensuring a uniform interpretation of the exemption across member states, nor in ensuring its use is subjected to robust regulatory oversight. One provision is particularly worrying, as it introduces the possibility of ‘an adapted pathway for less complex ATMPs’. This ambiguity could open the door to alternative authorisation pathways that bypass the EMA’s rigorous procedure to ensure safety and efficacy.

Regulating genetically modified organisms 

Another key area ripe for change is how the EU’s rules for genetically modified organisms (GMO) are applied to ATMPs. The current system in place is onerous. Developers must comply with differing rules on GMO applied by member states, making multi-country clinical trials burdensome. However, signs from the leaked draft are positive and indicate a move towards greater harmonisation. It appears that the Commission intends to separate GMO requirements for medicines from those for crops, and assign oversight to the European Medicines Agency, which is encouraging. However, it would appear that the legislation will fall short of granting an exemption from GMO requirements to ATMPs. ARM’s view is that GMO assessment in the EU should align with rules in other jurisdictions, such as the US, the UK, and Japan, in order to efficiently accelerate clinical trials. 

Creating a better future

ATMPs are complex to develop, but they offer hope for people with few – or no – other effective treatment options. To reap the benefits of existing therapies and to continue to develop new therapies for the future, an EU framework is needed that both protects patient safety and encourages a competitive market.

About the author

Paolo Morgese is head of Public Affairs, Europe at the Alliance for Regenerative Medicine. He is an expert in patient access, healthcare policy, and investment, with more than 20 years of experience in both assessing and supporting access to innovative healthcare technologies. Before joining ARM in 2017, Morgese worked for five years at Deerfield Management, a healthcare investment company. Prior to that, he worked at Merck Serono, Kyphon (which became Medtronic), and also spent several years with the Italian HTA Agency Agenas. His interests and expertise are centred on cell and gene therapy value assessment, healthcare system modernisation, and financing healthcare innovation.