Written by:
Gianluca Pirozzi
SVP, Head of Development, Regulatory and Safety, Alexion AstraZeneca Rare Disease
Rare diseases collectively impact millions of people around the globe — more people than cancer and Alzheimer’s Disease combined — yet most of these conditions have limited or no treatment options.1-4 But why is this? Research in this space often comes with additional complexity, because individual patient populations are small and many rare diseases are not well understood. By following the science to find innovative solutions and by integrating valuable insights directly from the best source of knowledge possible – the rare disease community itself – we are committed to leading the way in rare disease research and development (R&D).
Recognising the challenges in rare disease research
Science is hard and requires tenacity, grit and curiosity — something that is especially true for rare disease research and clinical development. There are approximately 10,000 known rare diseases, yet less than 10% have approved treatments.5
Advancing clinical research in rare diseases can mean navigating uncharted territory from the beginning, as often there is limited knowledge of the natural history or underlying biology compared with more common diseases. Clearly defined clinical trial roadmaps and regulatory pathways seldom exist. Endpoints – or defined clinical measures – often haven’t been established. And patient populations are small and widely dispersed, making it difficult to study a condition. Delayed diagnoses or misdiagnoses can further exacerbate challenges by making it difficult to find potential participants for clinical trials.
Embracing a patient-centric approach
Clinical innovation in rare diseases requires deep expertise and close collaboration across multiple groups, including with patient communities, key opinion leaders and specialist clinicians. It’s not enough to understand only the biology of the disease; it’s critical to also understand the impact it has on the lives of patients and their families. Patient perspectives help us understand their unique needs and the challenges they face, so we can design and deliver clinical trials that are suitable for them.
In one of our trials for patients living with neuromyelitis optica spectrum disorder (NMOSD), for example, we navigated multiple hurdles to ensure patients’ needs were prioritised.
NMOSD is a rare autoimmune disease characterised by relapses that can lead to cumulative disability and premature death.6 With approved and effective treatment options available, including a placebo arm in the trial would not have been in the patients’ best interest, as it could increase their risk of long-term complications. As a result, a randomised control study comparing an investigational treatment with placebo was not an option.
This disease also has a low diagnosed prevalence, making a traditional head-to-head trial comparing two different therapies unfeasible. This is because the number of patients needed for the trial would have exceeded the number of people living with the disease.
In response, we approached regulators with a proposal for an innovative open-label trial design that utilised a historical control group from a prior trial for this indication (instead of a placebo group). Using extensive statistical analyses, we would account for any potential differences of treatment effect. Global health authorities agreed that designing the trial in this way would maintain scientific rigour while putting patients’ needs first.
Because of this innovative, patients-first trial design, there was significant interest from the patient community. The creative and collaborative clinical trial design approach helped navigate challenges of a small patient population while still evaluating endpoints that mattered most to the community.
Advancing the science to benefit the rare disease community
Working in rare diseases requires researchers to think differently about R&D, and we remain committed to leading the way through expertise that stems from a deep understanding of the patient experience.
We continually strive to design clinical trials that reflect patients’ and caregivers’ lived experiences and reduce the burden of participation. We were the first to adapt the Patient Friction Coefficient for rare diseases – helping us standardise how we assess and reduce patient burden, evaluate trial design and protocol feasibility, and identify factors to improve the performance and efficiency of trials.7
We are also committed to shortening the diagnostic journey, which is one of the most significant challenges facing the rare disease community.4 Through our collaboration with Rady Children’s Institute for Genomic Medicine, we are providing strategic leadership and technical expertise as they work to enhance and scale innovative newborn screening technology for hundreds of genetic diseases, so patients can get answers faster.
We continue to harness our deep expertise and relationships across the community to pioneer new approaches to accelerate the discovery and development of the next generation of therapeutics.
