Thirty years ago, the Orphan Drug Act helped transform how pharma approached rare disease research. Before 1983, few companies made rare disease research a priority, even with 25 million US residents being affected. The change came gradually, but scientific breakthroughs such as precision medicine and gene therapy have escalated efforts to treat patients with rare diseases. In fact, more than 5,000 rare disease trials started in 2021, which highlights the importance of rare diseases to corporate pipelines.
Even with this uptick, many fail to realise the different approaches that companies must take to deliver value in a rare disease clinical trial compared to general medicine trials. Unique factors can determine whether a rare disease trial delivers on its potential and leads to a new treatment. With hard-to-secure long-term funding needed and small patient populations that are hindered by geography, and patient demographics, companies must determine which success factors to leverage in their trials.
When handled correctly, rare disease clinical research can yield scientific breakthroughs, new treatment perspectives in the disease area and ancillary treatment insights across more common diseases.
Rare disease research has massive implications today. Since 2018, big pharma has either acquired or developed 50% of new orphan drugs approved by the FDA. The reason is simple: while each rare disease might have a small patient population, more than 350 million people worldwide are affected by an estimated 10,000 rare diseases.
Companies that strive for efficiencies and excellence in their rare disease trial programmes often follow a consistent set of practices. These include long-range planning and scenario planning that is conducted early on that helps mould clinical protocols and ensure that the trial meets pre-specified outcomes and reaches study completion.
Also, best-in-class companies embrace innovation, overcome access and availability challenges, frame tight inclusion/exclusion criteria and promote disease awareness. From a Medical Affairs perspective, the initial rare disease trial efforts can have implications for years.
First, new scientific knowledge can reach healthcare professionals (HCPs), patients, caregivers, advocacy groups and others. Next, it helps establish deep disease understanding around the science as researchers define the unmet need, uncover the treatment pathway and identify any pathway gaps. Finally, the research sets guard rails for the initial medical communication and education that must occur.
Bringing novel rare disease therapies and drugs to patients takes vigilance. Cognitive and physical disabilities can restrict trial participation and small patient populations can hurt identification for trial recruitment, with other impediments including travel distances from trial sites and limited healthcare access in rural areas. With this in mind, there are four areas that companies can focus on to improve their efforts.
- Embrace innovation
Traditional trial design can limit effectiveness in rare diseases, so non-traditional trial models such as umbrella and basket trials should be considered. These models expand target populations without limiting the disease subtype being studied. Unfortunately, few companies have taken this route. A December 2021 analysis from Clinical Trials Arena found seven umbrella trials and 42 basket trials were initiated that year compared to 5,000-plus rare disease trials. - Overcome access and availability challenges
Improved diagnostic tools and education for general practitioners can lessen geographic hindrances to treatment, as can tools such as telemedicine, expanded trial sites and multidisciplinary networks to support and inform patients of trial opportunities. - Frame tight inclusion/ exclusion criteria
Creating tight exclusion/inclusion criteria and well-validated endpoints can improve targeting for rare disease trials. Clear, definable endpoints can be the difference in the two or three patients that positively or negatively impact the results. Trial designers should spend time early on reviewing inclusion/exclusion criteria to make participation productive. - Promote disease awareness
Earlier build-out of medical affairs resources and teams will allow for the earlier promotion of disease awareness. This includes the critical role medical affairs relationship development can play with patient advocacy. Patient advocacy groups provide expanded reach in rare disease patient populations. When pharma companies work with the advocacy groups, they can grow the disease awareness needed to support the stakeholder ecosystem.
The long-term value of rare disease trials and their treatments will continue to evolve over time, and continuous measurements around trial recruitment and retention can be adopted in new studies. Ultimately, companies must continue to prioritise the development of rare disease drugs as we seek to address the most debilitating diseases known.
Continued improvements and efficiencies in recruitment and retention will allow for greater targeting for diseases that have even smaller sizes than those traditionally researched in the rare disease space. And the carry-over effect of treatments and learning to general disease will continue to improve treatment across all diseases in the global market.
References are available on request.
