What is the biggest barrier to rare disease drug development?

February 28th marks Rare Disease Day. In keeping with the theme, EPM asked Dr. Asma Patel, vice president of integrated services for early development at Quotient Sciences, what barriers remain in rare disease drug development and the strategies that can bring the much-needed drugs to market faster.

Despite improvements in regulatory support and commercial rewards, difficulties remain for drug developers in bringing rare disease drugs to market. There are four main barriers impacting the development of orphan programs: (1) increasingly constrained R&D budgets, (2) challenging product development, which may need to be specialised on a per patient basis, (3) problematic clinical recruitment in rare patient populations and (4) regulatory hurdles in striving for fast track and accelerated approval.

Quotient Sciences has extensive expertise in working with rare disease programs, with over 50 orphan drugs developed in the last 5 years. We have addressed the challenges in this unique space through strategic approaches that have been proven to accelerate development timelines, minimise risks and reduce costs in getting these medicines to patients.

• In early-phase development it is critical to ascertain a thorough understanding of the drug’s physico-chemical and biopharmaceutical properties from the outset, enabling a data-driven approach for formulation design to facilitate adoption of efficient and active pharmaceutical ingredient (API) conserving approaches.  
• Utilising an integrated approach for development can improve the likelihood of downstream clinical and commercial success. The integration of real-time manufacturing and clinical testing, known as Translational Pharmaceutics allows rapid accelerated optimisation and validation of drug product performance in humans. Formulation flexibility can be embedded within first-in-human (FIH) trials to enable “patient ready” formulations to be identified and ready for proof-of-concept (POC) studies in less than 12 months.  
• Understanding complexity in supply chain for rare diseases i.e. slow and sporadic patient recruitment and thus protracted clinical studies. Being able to provide a more tailored and bespoke drug substance and drug product manufacturing approach ranging from traditional large batch manufacturing, bright stock distribution and personalised manufacturing to individual patient needs (e.g. dose adjustments based on subject age/weight) is key.  
• Finally, to fast-track time to approval and market, adoption of rapid scale-up and commercial manufacturing for low-volume products is key. Technical expertise and globally integrated departments drive seamless drug product phase transitions from gram to multi-kilogram quantities. Identifying and understanding the critical quality attributes (CQAs) and critical process parameters (CPPs) earlier in formulation development to ensure successful scale-up. Quality by design (QbD) and design of experiment (DoE) approaches are also implemented to help ensure the development of robust processes and methods.