What are the challenges in developing new therapies for rare diseases?

With 350 million people affected worldwide, rare diseases represent a major unmet medical need. There is, however, no cure for the majority of rare diseases and many go undiagnosed.

Characterised by small, highly heterogeneous patient populations, including children in almost half of the cases, rare diseases are usually genetic and therefore chronic. The lack of natural history data poses several key challenges in the development of new therapies, such as:

• The design of a rigorous pre-clinical and early drug development plan
• The selection of appropriate biomarkers and treatment outcomes
• The design of clinical trials that can generate substantial efficacy and safety data and motivate patients. Can you give us some insight
  to recent discussions around endpoints for rare diseases?The selection of appropriate endpoints is crucial to provide substantial evidence of the efficacy of a drug. Unfortunately, for many rare diseases, well-characterised efficacy endpoints are not available, therefore the responsibility resides with sponsors to select or develop trial endpoints based on their knowledge of the disease and the clinical characteristics of the patient population selected for the clinical trial.

In its updated draft guidance on rare diseases published in February 2019, the US Food and Drug Administration (FDA) encourages pharma companies to involve patients, caregivers

and advocates in the drug development process, including endpoint selection.

In order to support future clinical trial development in rare diseases, the agency also planned to hold a public meeting on 29 April to collect patients’ and caregivers’ perspectives.

What are some recruitment/ retention challenges unique to rare disease studies?

Timing and the number of available patients are the main challenges for any rare disease study. When there are fewer patients, it becomes challenging to narrow inclusion criteria based on the stage of the disease or other factors. Patients are located all over the world and this requires multicentre and multinational partnerships to be successful. In addition, due to the patients’ potential remoteness, as well as their possible physical limitations, travelling to a research site may be an enormous barrier to participation. For studies using repurposed drugs, participation can be compromised by off- label usage outside a controlled research setting.

What are some solutions to these challenges that are most effective in rare disease studies?

The most effective solution to mitigating all the aforementioned challenges is to have a well thought-out strategy with a multifaceted approach. This approach must include the consideration of the following for all rare disease trials:

* Patient-centric perspective – gathering as much information directly from the patients and/or their caregivers as possible about their experiences and using that information to either inform study design and/or determine best options to maximise participation

* Partnerships with patient organisations, advocacy groups, patient registries and clinician education to increase disease awareness, minimise time to diagnosis and identify viable patients for the study

* Exploration of telemedicine, home nursing and patient travel concierge as essential elements of assisting with participation

* Tools to ensure close partnership and communication with research staff and families to facilitate the best possible patient experience.

Making it easier for the patient to participate in the clinical trial is essential to engage and support the patient throughout their journey.