Out-Law Analysis 5 min. read
16 Feb 2022, 2:01 pm
Businesses have a rare opportunity to shape changes in EU law and policy that could make it less costly to develop and commercialise transformative new treatments based on human cells or genes.
The opportunity arises at a time when EU law and policy is evolving and significant reforms to legislation impacting cell and gene therapies (CGTs) are on the horizon.
CGTs have made impressive clinical progress and Europe has made great strides toward harnessing the potential of CGTs as the science and the industry that supports it steadily progresses. However, barriers to more widespread adoption remain. Overcoming these barriers is no small task. A major barrier is cost – CGTs will only be more widely adopted in Europe if costs come down.
Technological advances and new ways of working can help businesses tackle the cost issue in part, but policy, regulation and legislative change is also necessary to make commercialisation of CGTs viable. Without such developments, cost will continue to be a barrier to widespread adoption and in the longer term may negatively impact on investment in the sector.
The good news is this is a problem that appears to have been recognised by EU policymakers and regulators.
This is a once-in-a-generation opportunity to drive regulatory and legislative changes across the EU to support development and improved access to CGTs
While the European Medicines Agency (EMA) has published useful guidance and flowcharts to help businesses navigate existing regulatory requirements, the European Commission has been considering future legislation, regulation and policy.
The Commission’s pharmaceutical strategy, published in November 2020, represented a tangible step towards change. In the paper, the Commission identified CGTs as “milestones of major progress in medical treatment” but stressed the need to improve “the availability and affordability” of medicines, as well as EU health systems’ sustainability. Below, we explore three areas that the Commission identified for action.
One of the problems the Commission identified was the national “silos” that exist within the EU. It identified the need for greater cross-border cooperation among public health bodies, including in relation to pricing and reimbursement of medicines – decisions on which are a matter for each individual EU member state.
The fragmented EU market can make reimbursement a complex, lengthy, and costly process, as CGT companies must negotiate terms with every country and, in some instances, with regional authorities within a country too. This has a number of practical implications for CGT developers, including differences in reimbursement schemes and timelines.
Chimeric antigen receptor T (CAR-T) cell therapies, Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel), are two examples that demonstrate the different and novel approaches to reimbursement being adopted across Europe to manage the data uncertainty and address the affordability challenges of CGTs. After EMA approval in August 2018, these therapies achieved reimbursement in a number of European countries over 2019. The reimbursement and funding schemes used for Kymriah and Yescarta in five European markets, France, Germany, Italy, Spain, and the UK, were reviewed in a study by the UK’s Cell and Gene Therapy Catapult.
Steps have been taken to try to streamline the pricing and reimbursement negotiation process through collaboration between some European countries in the form of the Beneluxa initiative.
The aim of the initiative is to increase patient access to innovative therapies, including CGTs, through various strategies including by participating countries exchanging expertise on pricing and reimbursement and providing transparency on pricing as well as through mutual recognition of health technology assessments (HTAs). Belgium, Netherlands, Luxembourg, Austria and Ireland are all participants. Some success has been achieved, with Belgium, Ireland and the Netherlands reaching an agreement on the pricing of Novartis’ Zolgensma via the initiative.
To build on this, the Commission in its pharmaceutical strategy for Europe said it would “foster transparency of price information to help member states take better pricing and reimbursement decisions, also considering possible knock-on effects for innovation”. It added that it would also “support mutual learning through information and best-practice exchange, including on public procurement and the coverage of pharmaceutical costs by social protection systems, price-increase criteria and rational prescribing”.
Health technology assessments (HTAs) are holistic assessments of the medical, social, economic and ethical issues associated with introducing new health technologies, whether medicines, medical devices, surgical procedures or other measures for disease prevention, diagnosis or treatment used in healthcare. The assessments aim to establish, among other things, how effective prospective new health technologies are relative to those already on the market, as well as what added value they might deliver.
A new Regulation on Health Technology Assessment – an important deliverable of the pharmaceutical strategy – entered into force in January 2022. The Regulation aims to give developers more clarity and predictability on the clinical evidence requirements for HTA across the whole of the EU, although critics say it fails to deliver “a predictable, efficient, and non-duplicative system”.
Currently in the EU, if a business wants to market a new health technology it must go through separate HTAs within each EU member state. Each HTA is conducted in accordance with different national processes and methodologies, and developers of health technologies are commonly confronted with multiple requests from assessment bodies for data and other evidence in support of their products.
The Regulation introduces new EU-wide joint scientific consultations, to advise technology developers on clinical study designs, and a new EU joint clinical assessment (JCA). Under the JCA process, EU member states will retain responsibility for determining the additional clinical benefit of a new medicine and making pricing and reimbursement decisions, but that will be based on a new centralised assessment of the clinical evidence – including the strengths and limitations of available data and relative effects for health outcomes.
The JCA process will be introduced in a phased approach, starting with cancer therapies in 2025. This will then expand to include orphan drugs and advanced therapy medicinal products (ATMPs) by 2027. Clinical development programmes for CGTs predicted to launch from 2027, 2025 for cancer therapies, should align with JCA requirements as the outcomes from this assessment may inform the clinical value assessment and pricing and reimbursement throughout EU member states. However, ATMP manufacturers should also anticipate ongoing requirements for national level HTA submissions as member states may complement the JCA with additional clinical analyses for their national HTA process as well as non-clinical analyses.
Another core commitment of the Commission’s from the pharmaceutical strategy is to foster a system of incentives and obligations that supports innovation, access and the affordability of medicines across the EU.
To support its plans, the Commission has been considering how it might reform the EU’s general pharmaceuticals legislation. Its review was open to public consultation until December 2021.
The review needs to be considered alongside the overdue legislative proposals for revision of the EU orphan and paediatric regulations, expected at the end of 2021, and the ongoing review of intellectual property (IP), including incentives such as supplementary protection certificates.
Incentives for CGT products, including those addressing unmet needs in rare diseases and in the paediatric population, are under consideration as part of this review. The Commission is expected to table formal proposals for legislative reform before the end of 2022.
Other proposed policy changes potentially of interest are proposals for priority review type vouchers although the Commission’s proposal for the time being seems to be restricted to anti-microbials.
The desire of EU policymakers to improve market conditions and promote investment in CGTs is evident from the European Commission’s various initiatives, but it remains to be seen whether the reforms already finalised and the others in the pipeline go far enough to positively impact costs.
There is still time for businesses to influence EU policy and legislative discussions. We advise businesses to monitor for developments and to actively engage with policymakers – this is a once-in-a-generation opportunity to drive regulatory and legislative changes across the EU to support development and improved access to CGTs.
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