Enabling the Future of Cell & Gene Therapies through Non-Proprietary Patient-Owned Data Collection
This paper explores the primary issues and requirements for data gathering that cell and gene therapy developers face. It also considers solutions, and the role a standardized non-proprietary data collection platform, such as RARE-X, can play in addressing these challenges.
There is a substantial unmet need for therapies to treat rare diseases. For as much as 95 percent of the 7,000 to 10,000 rare diseases that exist, there are no approved therapies today. But as researchers come to understand the genetic basis for many of these conditions, new approaches are rapidly advancing to treat them.
Cell and gene therapies have emerged as a new treatment paradigm, and with them has come the potential to alter the course of many rare diseases. In many cases, there is an opportunity to correct the underlying dysfunction with a one-time administration of a therapy and provide either a functional cure or a substantial improvement in health outcomes. In other cases, long term symptom relief will be the primary therapeutic objective. Some of these indications may require more than one dose to achieve continued symptom relief and scientists and companies are working on technologies that will enable the use of a repeat dose.
While developing a therapy for a rare disease can be challenging, gene and cell therapies face additional hurdles. These innovative technologies intended to address monogenic or polygenic rare diseases with potential for lifelong positive outcomes with their single or repeat administrations face more extensive regulatory requirements, as well as the need to address issues presented from payers, providers, and patients regarding the durability and long term safety of these new therapies. For example, regulatory bodies require follow-up studies of up to 15 years to understand the effects of these in vivo and ex vivo approaches to disease amelioration. Much like the innovative approaches to treat disease, data collection also needs to be innovative. The ability to collect data, develop real world evidence and disseminate and share the data has to be modernized to keep pace with the development and regulatory needs.
This paper explores the primary issues and requirements for data gathering that cell and gene therapy developers face. It also considers solutions, and the role a standardized non-proprietary data collection platform, such as RARE-X, can play in addressing these challenges. The paper finds:
It is critical for all stakeholders to recognize the shared need for data for cell and gene therapies extends across patient organizations, providers, payers, regulators, and developers. Rather than each of these stakeholders seeking to tackle the challenge on their own, experts across the ecosystem have recognized that patient organizations are best situated to gather the data needed by stakeholders and ensure that it is appropriately shared with others. The challenge, though, is that patient organizations are stymied by the cost, lack of infrastructure, and access to the expertise needed to build robust data sets that can meet the demands of regulators. New and re-imagined data collection and sharing through non-proprietary platforms can address these challenges.
RARE-X is a nonprofit that is enabling rare patient communities to gather, structure, and securely share critical data through a common platform. The organization is leveraging existing technology powered by the Broad Institute of MIT and Harvard and designing its platform to adhere to Global Alliance for Genomics and Health (GA4GH) standards to facilitate global data sharing. It is working to remove one of the greatest obstacles to progress in rare diseases by eliminating barriers for patients to gather, structure, engage, and responsibly share research-ready data with scientists, drug developers, and clinicians.
RARE-X provides infrastructure for a rare disease community to build a registry without having to create and resource it themselves. It also provides standardization tools so that datasets can be integrated where possible. And RARE-X offers operational support to ensure patient organization data are robust and meet the needs of developers, regulators, and payers.
RARE-X is not competing with alternative providers but offers a way for any data owner to collaborate with others by using its federated data platform. A federated data system is a meta-database made up of connected databases. The databases remain independent and self-contained, but they are transparently connected and can be queried together. Such a framework allows for the sharing of large datasets from around the world, which RARE-X believes will be critical to driving advances for rare disease researchers, as the value of data increases in the aggregate.
When the U.S. Food and Drug Administration approved Zolgensma in 2019, the first gene therapy to treat children less than two years of age with the most severe form of the rare genetic neuromuscular disease spinal muscular atrophy, it signaled the promise of how this new class of therapies could transform the lives of patients with the progressive and deadly rare disease. SMA type 1 is the leading cause of genetic death in infants. Left untreated, the muscles of children with the condition grow weaker over time. More than 90 percent will require the permanent use of a ventilator or die by the age of two.
Zolgensma works by replacing the defective or missing SMN1 gene that underlies this deadly condition in these infants with a functional version of the gene. It can halt progression of the disease by providing sustained expression of the SMN protein with a single, one-time treatment. The case of Zolgensma is not only a leap forward in our ability to transform rare diseases, but a reminder of the critical role patient data can play in the development of cell and gene therapies. The FDA approved Zolgensma based on a single-arm study that used available natural history data of patients with infantile onset SMA as primary evidence of the effectiveness of Zolgensma.
The data gathering will continue long after approval for Zolgensma’s marketer Novartis Gene Therapies, which now must collect long-term follow-up data on patients treated with the gene therapy. Gene therapies, unlike traditional medicines, command a high one-time or installment-based payment (Zolgensma has a price tag of $2.1 million) but are expected to provide long-term benefits. Although they may offer better value for money, and their price may be less than the cumulative cost of chronic care, the high up-front cost is difficult for today’s healthcare system to absorb. And because these therapies are relatively new, there is limited experience to understand how lasting their benefits in the real-world will prove over time. Gene therapy companies need to address questions by regulators, payers, providers, and patients about the long-term safety and efficacy of these new types of therapies, understand their performance over time, and determine their true value.
“Gathering requisite data to enable long-term follow-up of patients receiving cell and gene therapies is difficult given the lack of sufficient registries and monitoring systems optimized for this requirement,” said Morrie Ruffin, co-founder and board member of the ARM Foundation for Cell and Gene Medicine. “There is a need to create new tools and methods for this purpose that could be standardized to meet regulatory and health technology assessment long-term follow-up requirements that integrate real-world evidence obtained directly or remotely from patients with electronic health records and claims data.”
The ARM Foundation, in partnership with RARE-X, convened experts in real world evidence strategy and operations from industry and the patient community to better understand these challenges and how they could be addressed through common registry platforms designed specifically for long-term follow up. Their ideas and recommendations are featured in this white paper.