Rare disease research was once a neglected aspect of pharmaceutical research, relegated to non-profits and philanthropic projects. But in today’s research environment where blockbuster drugs are few and far between, regulators are incenting developers to pursue unmet needs, drug targets are increasingly being elucidated and pharmaceutical companies are investing billions into rare disease research – all with impressive results.
For example, the U.S. Food and Drug Administration (FDA) approved 21 drugs for rare diseases in 2015 and nine in 2016. Last year’s list included the first treatment for patients with spinal muscular atrophy and the first drug approved to treat Duchenne muscular dystrophy (DMD). Additionally, 582 applications for orphan designation were received by the FDA in 2016, an increase of over 100 from 2015, signally great hope for more treatment options in the near future.
This is great news for the millions of people who suffer from rare diseases that often have few if any treatments. Though it also creates significant challenges for the biopharma companies conducting this research, particularly if they are accustomed to running trials for conditions that affect millions of people worldwide.
Rare diseases have small and often widely scattered populations, so recruiting patients to trials can be extremely challenging. The lack of natural history data, suitable animal models of disease, regulatory guidance, agreement on primary and secondary endpoints, as well as genotypic and phenotypic variability within the same disease, all make it very difficult to define common treatment patterns, assess how those treatments are working, and identify gaps – all of which is vital to the clinical research process.
There are no silver bullet solutions to overcoming these challenges but they can be addressed, in part through patient registries.
A rare disease patient registry, a rich source of real-world data, would be an online platform where physicians, patients and caregivers can record clinical and related information about a patient’s diagnosis (including genetic or confirmatory diagnostic data), condition progression and treatment experience.
Over time, the data collected would provide researchers with a valuable glimpse into the patient experience with the disease that cannot be gleaned from simple laboratory or physician assessments. It also could help identify patients – given the correct risk/benefit ratio as deemed by the patient’s caregiver team – for potential enrollment in clinical trials.
These insights can help shape the direction of an investigation, and give researchers a place to share information about their studies with physicians, patients and advocacy groups, and more efficiently and cost-effectively recruit participants to their trials.
Many pharma companies are now using these registries to optimize their rare disease programs. For example, True North Therapeutics, launched the COMPASS registry in March 2016 to support efforts to develop novel therapies for Cold Agglutinin Disease (CAD). Later that year, Blueprint Medicines rolled out Mast Cell Connect, a registry for patients with mastocytosis, a rare disorder caused by a buildup of immune cells in the skin, bone marrow, and organs. In February 2017, the FSH Society announced that their newly formed fascioscapulohumeral muscular dystrophy (FSHD) consortium is working to consolidate more than 13 patient registries in an effort to accelerate research in rare disease.
Best practices for rare disease registries
These platforms can serve as a powerful resource tool for researchers, but only if they are integrated into the research plan from the start and designed to deliver value throughout the development lifecycle. Before building a registry, developers should consider what data they want to collect, who will enter the data, how the data will be updated and/or shared and how it will add value at every stage of the drug development process.
The best time to build a registry is before the research begins or, if not possible, as early in the development process as possible. This gives developers the time to build out a robust population, and gather meaningful baseline data on the current state of the disease and the impact of existing treatments. This early data also can be used to choose trial sites based on patient location, and to validate primary and secondary endpoints, which is critical in rare disease studies where meaningful endpoints are often undefined and must be validated.
Over time researchers can use the registry data to:
- Track quality of life changes in patients using a new treatment
- Make comparisons among patients on different regimens, or who have varying genetic backgrounds or co-morbidities
- Track things like adherence to protocol, and occurrence of side effects.
All of this data can be used to support label claims and pricing requests, giving regulators added proof that a drug meets safety and efficacy requirements.
After a rare disease drug receives commercial approval, registries can be used to demonstrate the real-world safety and efficacy of the drug. This is a common requirement for rare disease drugs, especially for those that receive accelerated approval and/or rely on smaller clinical trials for their initial or tentative approval. After initial approval, a larger confirmatory trial may be needed to corroborate the initial efficacy and safety seen in the smaller trial(s). For example, as part of the 2014 approval of Myalept as a replacement therapy to treat complications of leptin deficiency, FDA required developers to gather data through a long-term product exposure registry of patients as part of its Risk Evaluation and Mitigation Strategy. For the 2014 approval of Translarna (ataluren for the treatment of nonsense mutation of DMD), the CHMP required developers to conduct another clinical trial to support the renewal of its initial marketing authorization.
Regardless of when the registry is launched, researchers should take full advantage of the opportunity to connect with patients and key opinion leaders. These registries can become a hub for the patient community, but researchers need to give back to that community if they want to win their trust and support. That means listening to patient concerns, asking for their feedback, and sharing updates on study progress and outcomes. This ensures the patient community is aware of the work being done on their behalf, and lets them know that the research team values their input and participation.
Registries can be an invaluable tool to any clinical research program, but especially for rare disease research, they can act as a lifeline between patients, clinicians, researchers and the pharmaceutical sponsors trying to help them. Starting early, engaging patients, and understanding how this data can be applied to the drug development lifecycle ensures everyone involved with the registry will have access to new treatments as early as possible.