Rare Disease Day is a chance to recognise the progress made since the genomic medicine revolution, acknowledge the challenges of living with — and treating — rare diseases, and evaluate Europe’s preparedness to make the latest therapies available to patients.
Mark Battaglini, Chief Strategy Officer at Alliance for Regenerative Medicine; Stefano Benvenuti, Head of Public Affairs at Fondazione Telethon; Dr Androulla Eleftheriou, Executive Director at Thalassaemia International Federation.
This year, the rare disease community has a particular sense of urgency and opportunity as we unite to ensure that the EU Joint Clinical Assessment (JCA) will deliver durable, and potentially curative, therapies to rare disease patients with few, or no, other treatment options. Starting in January 2025 with Advanced Therapy Medicinal Products (ATMPs) and cancer medicines, the JCA will provide an EU-centralised alternative to the long-standing country-by-country approach to assessing the clinical benefit of newly authorized products.
In this article, three representatives of the rare disease community consider how to maximise the potential of the JCA to accelerate patient access to Advanced Therapy Medicinal Products (ATMPs), including transformative cell and gene therapies.
LIFE CHANGING THERAPIES DEVELOPED SINCE THE FIRST RARE DISEASE DAY, 25 YEARS AGO
Major advances in the diagnosis and treatment of rare diseases have been achieved over the past twenty-five years, significantly improving the prognosis of patients with conditions that were otherwise untreatable. By addressing the root cause of disease, rather than the symptoms, ATMPs have demonstrated long-lasting benefits after just one administration.
There are 26 ATMPs with marketing authorisation in the EU. Since December 2023, the first CRISPR gene-editing therapy has gained regulatory approval in the EU, UK, and the US for the treatment of sickle cell disease and beta thalassemia, while the pipeline for ATMPs has grown to nearly 2,000 clinical trials worldwide. These treatments have incredible potential for rare genetic diseases and rare cancers; it is imperative we do all we can to ensure that they reach patients as soon as possible.
SHAPING THE EU’S JOINT CLINICAL ASSESSMENT TO ACCELERATE ACCESS TO NOVEL THERAPIES
ATMPs mainly seek to treat rare diseases and cancers that cause premature death or serious disability, many of which are rare paediatric diseases. Small patient populations, lack of effective treatments, and the serious nature of many rare diseases make it impractical and sometimes unethical to conduct randomised control trials (RCTs), in which patients are randomly assigned to a treatment arm or a placebo arm. Clinical trials would also need to last years, and perhaps lifetimes, to demonstrate the full benefit of these next generation therapies.
New methods are needed to evaluate the durable, and potentially curative, impact that they can deliver in a single dose. The JCA is an opportunity to design best-in-class methodologies that are fit-for-purpose for these new medicines, including allowing for the use of evidence from single-arm trials, observational trials, real-world, and other sources of data beyond the typical RCTs, that are designed for conventional medicines. One possibility is to use synthetic control arms, which leverage data from disease registries, to compare to the results of a single-arm trial. Any remaining uncertainty around the long-term benefit of ATMPs could be managed with risk-sharing arrangements with payers, including performance-based agreements.
Some national Health Technology Assessment bodies have already used indirect treatment comparisons when RCTs were not feasible, and the JCA should emulate such forward-thinking, pragmatic approaches. A one-size-fits-all approach focused only on RCTs as legitimate evidence of benefit could lead to inconclusive results for many rare disease ATMPs in the coming years, endangering access for rare disease patients across the EU.
Rare disease patients have invested hope, time, and energy, at some risk, to participate in clinical trials in search of a better life for themselves and their peers. The JCA should reflect their pioneering spirit with its own innovative approach, converting the learnings from a few into medicines that can benefit many more – while maintaining high standards for safety and efficacy.
“Gene therapy is our miracle. It has completely changed the direction of our lives and we will be forever grateful! Thanks to this miracle treatment our twin boys are living a very happy, healthy lifestyle, attending mainstream school and playing sports with their friends. They have now outlived their older sister who was symptomatic and therefore missed out on treatment. We truly hope and pray that this giant milestone will ensure that many more children will have the opportunity to access this treatment and live non-symptomatic, happy healthy lifestyles just like our boys”.
Leah, mother of Oscar and Phelix (UK), who received gene therapy for metachromatic leukodystrophy (MLD) in 2016. This therapy was developed at San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) in collaboration with Orchard Therapeutics and received marketing authorization in 2020.
CONCLUSION
In the Health Technology Assessment Regulation, the EU committed to developing appropriate methodologies for assessing ATMPs so that countries could more accurately judge their value. The HTA Coordination Group, which is developing the new methodologies, can deliver on this pledge by collaborating with the ATMP and rare disease communities. The EU has a momentous opportunity to build a modernized framework to deliver the future of medicine for patients — a future in many ways unimaginable on the first Rare Disease Day 25 years ago.
AUTHORS
Mark Battaglini, Chief Strategy Officer, Alliance for Regenerative Medicine
The Alliance for Regenerative Medicine represents the Advanced Therapy Medicinal Products (ATMP) community including patient groups, academic centres, foundations, and ATMP developers.
Stefano Benvenuti, Head of Public Affairs, Fondazione Telethon
Fondazione Telethon funds scientific research to give people affected by a rare genetic condition a new hope.
Dr Androulla Eleftheriou, Executive Director, Thalassaemia International Federation
The Thalassemia International Foundation works for the treatment, prevention and cure of thalassaemia.
Source: Euractiv.com
