Development of novel therapies

How can Europe speed up development of therapies for the 95% of rare diseases with no authorised treatment?

Today, a significant share of the rarest diseases lacks an approved treatment

Significant progress in the treatment of rare diseases has been made following the introduction of the OMP Regulation in 2000. Today, approved treatments exist for around 5% of rare diseases. 

While this is a success, 95% of rare diseases remain without an authorised treatment. The lack of authorised treatment mostly concerns the rarest diseases. In fact, 79% of rare disease patients suffer from 149 of the most prevalent rare diseases, with prevalence between 1 and 5 in 10,000. Many of these diseases have an authorised treatment. The challenge for the next two decades is continuing the positive path for all rare disease patients and developing treatments for those affected by the rarest diseases.

New technologies bring opportunities

Developing innovative medicines starts with science. Recent years’ advances in gene therapy are particularly relevant for people living with a rare disease, with 71.9% of those being genetic and 69.9% with exclusively paediatric onset. This has opened opportunities to treat, possibly cure, people living with rare diseases that previously were left without hope of improving their health status. This is promising but it comes with challenges.

But development times are inherently long

One key feature of these rare diseases is the small patient population. This means that fewer people with a rare disease can participate in clinical trials and contribute to the generation of data on clinical outcomes. The risk of failed trials increases. In fact, just 1 in 10 phase 1 clinical trials for all medicines will eventually lead to an approved medicine. While still contributing to advancing knowledge on rare diseases, the remaining 9 failed clinical trials represent a lost opportunity to utilise scarce resources for clinical research.

Furthermore, with fewer patients the statistical power of clinical trial data decreases, which may reduce the relevance of the data in the eyes of regulatory authorities, HTA bodies and payers. Such data challenges will often lead to long development times because OMP developers need to produce additional data or change the trial design. An example is of an OMP, the first to treat a particular rare disease, that obtained Marketing Authorisation in 2022, 23 years after the first clinical trial was initiated.

Developing a successful treatment, including for the rarest diseases where no authorised treatment exists, takes time and resources. While more resources are necessarily required to address unmet needs, there is a potential to speed up development through new ways of working together along the OMP development path from basic research to market authorisation.

Partnerships is the key concept

Partnerships is likely to be the most impactful concept to speed up the development of innovative medicines. Finetuning existing incentives within the legislative framework is needed but not sufficient. Instead, partnerships can move the needle towards treating all people living with a rare disease.

Traditionally, medicine development and approval have been characterised by a developer-approver relationship that is based on bilateral incentives and a transactional approach. It has worked well for the past 20 years, incentivising OMP developers through e.g. Orphan Market Exclusivity and Orphan Drug Designation. However, if we are to bring innovative medicines to those living with the rarest diseases faster, a more collaborative approach is needed. This is because as the complexity of medicines development grows, so does the impact of the actions of one party on the other party. Hence, a transactional approach will yield inferior outcomes, which in this context means lengthier and costlier development to the detriment of all involved.

The opposite model is one of partnerships. EMA, HTA bodies, payers, OMP developers and patients must approach each other with a common problem-solving mindset aiming to bring effective treatments faster through clinical trials, authorisation and HTA processes. For example, this can mean re-organising their procedures concerning data requirements. If such procedures were imbued with common problem solving and the intention to bridge the gap between data requirements and the data that can be collected, development times could be shortened.9

For faster innovative medicines development, we have identified two crucial partnerships:

Public-private partnership for basic research

The lack of basic research is a key barrier to development for the rarest diseases.9 Boosting basic research requires more and smarter funding that leverages data and the integration of research communities across Europe. This ensures more effective and targeted research for every euro spent. An effective solution would therefore be a Private Public Partnership (PPP) fund focused on rare diseases to boost funding of basic research in underserved areas integrating learnings from platforms such as IMI, IHI and the European Joint Programme on Rare Diseases. Here, European Reference Networks (ERNs) have the potential of becoming an important platform.

Evidence partnership for better trial design

Another key barrier to innovation in rare diseases is the lack of clarity on requirements for the evidence needed to obtain approval by regulators and to demonstrate value with HTA bodies.9 Early, iterative dialogues between developers, EMA, HTA bodies and payers that follow a partnership logic will allow making feasible plans for the evidence required early on, therefore informing a more efficient clinical development. In such a framework, adaptive pathways can support faster access to treatment by accelerating patient recruitment. Similarly, digital solutions can allow for the inclusion of more outcomes and continuous monitoring.

The study is commissioned by Takeda.


Related work

European Expert Group on Orphan Drug Incentives Orphan medicine incentives