Advanced therapies – referred to as advanced therapy medicinal products (ATMPs) in the EU and as cell and gene therapies (CGT) in the US – are a class of products based on genes, tissues or cells used to treat or deliver treatment to patients. Since the first gene therapy for a rare paediatric leukaemia was approved by the U.S. Food and Drug Administration (FDA) in 2017, there has been mounting excitement that advanced therapies could help manage, or even provide a durable solution for, rare diseases. These ‘living’ therapies are designed to have long-lasting or permanent effects that restore biological function and address the underlying cause of disease. This includes genetic causes, which account for the majority of rare diseases.
The excitement around advanced therapies for rare disease has been amplified by the overwhelming, unmet need for treatment options. At present, 90 percent of rare diseases have no FDA-approved therapies. While there is a great need for rare disease advanced therapies, clinical development and subsequent market authorisation remains challenging. This blog discusses common hurdles and considerations for the clinical development of rare disease advanced therapies.
Rare disease clinical development
The primary challenges of rare disease clinical development, regardless of therapeutic class, include a limited patient population, wide geographic distribution of these patients and minimal preclinical data. Rare diseases are often poorly characterised, and have only a few specialists with the expertise to run a clinical trial. In addition, clinical trials must recruit from an extremely small population, and this population is often paediatric patients with life threatening conditions. The limited number of participants, paired with an ethical obligation to treat as many as possible, means that controls are designed to be very small or external to the trial. Great unmet need also means that rare diseases are often eligible for expedited market authorisation. Most commonly, the development pipeline for a rare disease involves a phase 1/2 combined trial, a phase 3 trial and market approval followed by patient follow-up and phase 4 trials.
Advanced therapy clinical development
Development challenges specific to advanced therapy clinical development include stringent regulations during manufacturing and production, and limited preclinical information to guide clinical trial design. Establishing manufacturing and quality standards is also a major challenge for advanced therapies, because their biological nature can pose unique risks, including immunogenicity and variable efficacy. In addition, animal models are unsuitable for preclinical studies, limiting preclinical data before first-in-human trials. Many advanced therapies also should not be tested on healthy volunteers, limiting first-in-human studies to the target population.
Advanced therapies specifically for rare diseases must navigate the compounding challenges faced in rare disease and advanced therapy development. A strategic regulatory strategy will help ensure that these therapies get the appropriate resources during development and consideration during market authorisation.
For more information on unlocking the potential of advanced therapies developed for rare diseases, read our whitepaper and check out our regulatory strategy blog.
In this section
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Digital Disruption
- AI and clinical trials
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Clinical trial data anonymisation and data sharing
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Clinical Trial Tokenisation
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Closing the evidence gap: The value of digital health technologies in supporting drug reimbursement decisions
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Digital disruption in biopharma
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Disruptive Innovation
- Remote Patient Monitoring
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Personalising Digital Health
- Real World Data
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The triad of trust: Navigating real-world healthcare data integration
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Patient Centricity
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Agile Clinical Monitoring
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Capturing the voice of the patient in clinical trials
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Charting the Managed Access Program Landscape
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Developing Nurse-Centric Medical Communications
- Diversity and inclusion in clinical trials
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Exploring the patient perspective from different angles
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Patient safety and pharmacovigilance
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A guide to safety data migrations
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Taking safety reporting to the next level with automation
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Outsourced Pharmacovigilance Affiliate Solution
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The evolution of the Pharmacovigilance System Master File: Benefits, challenges, and opportunities
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Sponsor and CRO pharmacovigilance and safety alliances
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Understanding the Periodic Benefit-Risk Evaluation Report
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A guide to safety data migrations
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Patient voice survey
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Patient Voice Survey - Decentralised and Hybrid Trials
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Reimagining Patient-Centricity with the Internet of Medical Things (IoMT)
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Using longitudinal qualitative research to capture the patient voice
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Agile Clinical Monitoring
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Regulatory Intelligence
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An innovative approach to rare disease clinical development
- EU Clinical Trials Regulation
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Using innovative tools and lean writing processes to accelerate regulatory document writing
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Current overview of data sharing within clinical trial transparency
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Global Agency Meetings: A collaborative approach to drug development
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Keeping the end in mind: key considerations for creating plain language summaries
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Navigating orphan drug development from early phase to marketing authorisation
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Procedural and regulatory know-how for China biotechs in the EU
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RACE for Children Act
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Early engagement and regulatory considerations for biotech
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Regulatory Intelligence Newsletter
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Requirements & strategy considerations within clinical trial transparency
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Spotlight on regulatory reforms in China
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Transfer of marketing authorisation
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An innovative approach to rare disease clinical development
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Therapeutics insights
- Endocrine and Metabolic Disorders
- Cardiovascular
- Cell and Gene Therapies
- Central Nervous System
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Glycomics
- Infectious Diseases
- NASH
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Oncology
- Paediatrics
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Respiratory
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Rare and orphan diseases
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Advanced therapies for rare diseases
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Cross-border enrollment of rare disease patients
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Crossing the finish line: Why effective participation support strategy is critical to trial efficiency and success in rare diseases
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Diversity, equity and inclusion in rare disease clinical trials
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Identify and mitigate risks to rare disease clinical programmes
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Leveraging historical data for use in rare disease trials
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Natural history studies to improve drug development in rare diseases
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Patient Centricity in Orphan Drug Development
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The key to remarkable rare disease registries
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Advanced therapies for rare diseases
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Transforming Trials
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Accelerating biotech innovation from discovery to commercialisation
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Ensuring the validity of clinical outcomes assessment (COA) data: The value of rater training
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Linguistic validation of Clinical Outcomes Assessments
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Optimising biotech funding
- Adaptive clinical trials
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Best practices to increase engagement with medical and scientific poster content
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Decentralised clinical trials
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Biopharma perspective: the promise of decentralised models and diversity in clinical trials
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Decentralised and Hybrid clinical trials
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Practical considerations in transitioning to hybrid or decentralised clinical trials
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Navigating the regulatory labyrinth of technology in decentralised clinical trials
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Biopharma perspective: the promise of decentralised models and diversity in clinical trials
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eCOA implementation
- Flexible delivery models
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Implications of COVID-19 on statistical design and analyses of clinical studies
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Improving pharma R&D efficiency
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Increasing Complexity and Declining ROI in Drug Development
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Innovation in Clinical Trial Methodologies
- Partnership insights
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Risk Based Quality Management
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Transforming the R&D Model to Sustain Growth
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Accelerating biotech innovation from discovery to commercialisation
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Value Based Healthcare
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Strategies for commercialising oncology treatments for young adults
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US payers and PROs
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Accelerated early clinical manufacturing
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Cardiovascular Medical Devices
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CMS Part D Price Negotiations: Is your drug on the list?
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COVID-19 navigating global market access
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Ensuring scientific rigor in external control arms
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Evidence Synthesis: A solution to sparse evidence, heterogeneous studies, and disconnected networks
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Global Outcomes Benchmarking
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Health technology assessment
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Perspectives from US payers
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ICER’s impact on payer decision making
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Making Sense of the Biosimilars Market
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Medical communications in early phase product development
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Navigating the Challenges and Opportunities of Value Based Healthcare
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Payer Reliance on ICER and Perceptions on Value Based Pricing
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Payers Perspectives on Digital Therapeutics
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Precision Medicine
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RWE Generation Cross Sectional Studies and Medical Chart Review
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Survey results: How to engage healthcare decision-makers
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The affordability hurdle for gene therapies
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The Role of ICER as an HTA Organisation
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Strategies for commercialising oncology treatments for young adults
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