Looking Beyond Rare Disease Day for Rare Disease Drug Development

Innovation has been the driving force of greatness in American medicine. Since the passage of the Orphan Drug Act of 1983, the U.S. Food and Drug Administration (FDA) has approved more than 800 drugs and biologics for rare disease indications. Looking at numbers alone for the last few years, the industry pushed through new drugs for 76 rare disease indications and hit a record number of drugs approved in 2018 – followed by 22 approved novel drugs and biologics with orphan drug designation in 2019. The strides have been remarkable.

The shape in which the industry has taken to prioritize patients with rare diseases with little to no therapeutic options have led to a handful of firsts – the first treatment for interstitial lung disease, the first gene therapy approved to treat children less than two years of age with spinal muscular atrophy, and the first triple combination therapy available to treat patients with the most common cystic fibrosis mutation. Despite these successes, there’s still more that can be done to optimize how rare disease drugs get from concept to patient.

As seasoned life science consultants specializing in regulatory and clinical guidance for early to late-stage life science companies, we have the opportunity to work on a range of therapies for rare diseases that challenge our thinking and precedent but force us to be open-minded and compassionate. Rare diseases are a big part of our business and now that Rare Disease Day has come and gone and with the COVID-19 pandemic in full swing, we wanted to pen out some key takeaways that we learned at the FDA’s meeting on “Supporting the Future of Rare Disease Product Development” and what we are seeing are important initiatives across our industry.

1. Natural history studies are meant to collect “information about the natural history of a disease in the absence of an intervention, from the disease’s onset until either its resolution or the individual’s death,” according to the latest “Rare Diseases: Natural History Studies for Drug Development” guidance from the FDA. Given that diseases can vary across patients, this type of information can be very useful when it is unethical to conduct a randomized trial. When planning for a natural history study, investigators should consider these tips:
   1. Conduct study early and broadly enough so that the information is available when needed for designing a clinical trial
   2. Set a broad enrollment criterion for the specific disease that you’re going after
   3. Ensure that the protocol for collecting the data fits the objective of the study
   4. Invest infrequent visits to gather the necessary data during the study
   5. Partner with epidemiologist, subject matter experts, and stakeholders who could have something compelling to add to the design of a clinical trial
2. Important initiatives that were created to help support rare disease drug developers have promoted efficient and well-informed development of treatments.
   1. The Rare Disease Registry Program (RaDaR) website from the National Center for Advancing Translational Sciences (NCATS) aims to “provide the rare diseases community with guidance on how to set up and maintain high-quality registries and enable rare disease patient organizations to better promote and support patient-focused research.”
   2. The Rare disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP) platform from the Critical Path Institute (C-Path) aims to provide data and analytics to aid in the understanding of rare diseases and to inform long-term drug development and support innovative trial designs.
3. Remain patient-centric through and through. It’s important to remember the hope that any small advancement could have on a patient population that has been living with little to no therapies for a rare disease. We advise that companies remain transparent and accessible to patients and advocacy groups.  Patient advocacy groups and their input could be instrumental to the clinical trial design and in understanding the interpersonal relationships and hardships that may arise as a consequence of the rare disease.

While it is clear that the FDA has a strong commitment to supporting innovation for rare diseases, there is still an obligation from industry to understand how diseases affect the daily lives of patients in order to assess commonalities and differences and design patient-centric trials with appropriate endpoints, measures, and tests that can determine a patient’s quality of life.