Joe Renny, Ph.D., Strategic Growth Leader, CatSci
Rare disease programmes are uniquely fragile: small patient populations limit trial enrollment, therapies often rely on complex modalities like gene and cell therapies, and the economics challenge traditional models of return on investment. To be sustainable, development must go beyond resilience and adopt an antifragile mindset, one that learns and grows stronger from uncertainty.
First, strategic diversification is critical. Rare disease supply chains often depend on single suppliers for specialized vectors, reagents, or technologies. Building redundancy and geographic spread reduces the risk of catastrophic disruption while ensuring continuity for patients who cannot afford delays.
Second, agile and modular manufacturing enable scale-appropriate production for therapies designed for inherently small patient groups. Flexible facilities, continuous processes, and digitalized operations enable efficient pivoting as science and regulation evolve, keeping costs manageable while maintaining quality.
Finally, sustainability by design is essential. Embedding green chemistry, resource efficiency, and ESG principles enhances affordability and trust, vital in rare diseases, where therapies are often high-cost and heavily scrutinised by payers and the public.
By embracing antifragility through diversification, agility, and sustainability, the industry can transform fragility into strength, delivering rare disease breakthroughs reliably while creating enduring value for healthcare systems and society.
Natalie Yivgi Ohana, Ph.D., Co-Founder and Chief Executive Officer, Minovia Therapeutics
Making rare disease drug development sustainable, particularly for cell and gene therapies (CGTs), is complex but critical. High costs, long timelines, and small patient populations create unique challenges. Key pillars for sustainability include:
- Early and Efficient Diagnosis: Rare diseases are often underdiagnosed, slowing trials and limiting market potential. Novel biomarkers can speed diagnosis, expand patient pools, enable earlier intervention, and reduce long-term costs. At Minovia, we are developing blood biomarkers to assess mitochondrial health against healthy baselines.
- Platform Approaches and Modularity: One-off solutions are costly. Reusable platforms, viral vectors, gene editing tools, cell therapies, or mitochondrial transplantation, enable economies of scale, reducing R&D and regulatory costs and creating a more sustainable model.
- Regulatory Innovation and Harmonization: Collaboration with regulators and patient groups supports adaptive trials, real-world evidence, natural history studies, surrogate biomarkers, and streamlined review processes, accelerating approvals and improving investment appeal.
- Collaboration Across the Ecosystem: Partnerships among academia, industry, regulators, and patients accelerate discovery, de-risk development, and build confidence in new therapies.
Claudio Hegenberger, M.D., Vice President, Clinical Affairs, Emerald Clinical Trials
Rare diseases are typically defined as those of low prevalence in the general population, usually being life threatening and chronically debilitating. New diagnostic tests and biomarkers clarify disease subtypes, but also add complexity regarding their varied treatment responses. That has led to the concept of “personalized treatments,” but the dilemma on how we can get there continues.
What all rare diseases have in common is that they mean a huge challenge for patients, as well as for the healthcare sector and the pharma industry. The patient’s long journey to get the right diagnosis and specialized social and medical support can limit the pool of eligible patients for clinical trials. The huge investment required to fund a robust clinical development plan results in high-cost medications if they reach the market.
Sustainability requires innovative, flexible and specialized actions. Accelerated regulatory approval pathways, incentives for prioritizing innovation in drug development, equity and affordability for improving access, reducing developing costs using AI and in silico design, agile trial methodologies, and collaborative development models (public/private, academia/pharma/patient associations), provide excellent foundations for the present and future improvement in what is the most important goal: better long-term quality of life for patients.
Lew Bender, Chief Executive Officer, Intensity Therapeutics
Making rare disease drug development sustainable requires considerations across scientific, financial, clinical, and regulatory dimensions. Companies should focus on rare diseases with a patient population large enough to enable trial enrollment within a reasonable timeframe with a manageable number of sites. An adequate market with proper pricing is needed for a good return on the development’s investment. Any drug candidate must also be supported by a plausible mechanism of action, ensuring it is grounded in sound science and capable of addressing the disease’s underlying pathology. Early evidence in a small number of patients can provide invaluable proof-of-concept data, de-risking investment and guiding registration trial design. Sustainability also hinges on collaboration with stakeholders. Engaging insurance companies and patient groups early in the development ensures that considerations around coverage, cost, and access are integrated into the program rather than emerging as barriers at approval. Finally, open and early communication between drug developers and the FDA is critical to establishing reasonable, clinically meaningful endpoints for approval. This alignment ensures that trial outcomes will translate into regulatory success. Taken together, all these steps create a balanced framework that makes rare disease drug development more viable while also delivering meaningful therapies to patients in need.
Venu Mallarapu, Vice President of Global Strategy & Operations, eClinical Solutions
Sustainable rare disease drug development relies on creating stronger foundations for how data are collected, managed, and analyzed. A key enabler is data integration: bringing together information from patient registries, clinical studies and real-world sources into unified data ecosystems. When data are aggregated across institutions and trials, the improved statistical power allows researchers to generate insights that would not be possible with isolated, fragmented datasets, a necessity for rare disease research, where patient populations are small.
Equally critical are harmonization and standardization. Rare disease studies often use different formats, terminologies, and collection methods, making cross-study comparison difficult. By adopting common data models and consistent standards, organizations ensure that diverse datasets can be combined for robust analysis. Finally, advanced analytics and infrastructure give these unified datasets their true power. Cloud-based platforms, scalable architectures, and modern AI/ML methods enable teams to manage the complexity of rare disease data, detect patterns and identify potential treatment pathways earlier. These capabilities not only enhance efficiency but also allow research teams to make critical safety and efficacy decisions in real time.
Together, integration, harmonization, and advanced infrastructure create a sustainable framework that drives meaningful progress in rare disease drug development.
Michael Kadan, Ph.D., MBA, Chief Operating Officer, Vector BioMed
It is important to note the size and significance of this question. To make rare disease drug development sustainable, it takes all of us in biopharma and pharma, associated regulatory bodies, and payers. It involves everything from accessing industry knowledge to materials and process, and all the way through the clinical progression to patient access and go-to-market strategies that make sense for all parties involved. Principally, patients (and reimbursement). And, to simplify the response or pinpoint keys, let’s say affordability and sustainability are one and the same. It starts and stops with making rare disease drug development and cost of the marketed therapeutic affordable.
Success depends on a few critical enablers. Costs must be driven down. Developers must be given the tools they need, when and where they need them, with broader access enabled through technology simplification. Partnerships must be prioritized with organizations and stakeholders that put patient care over profit, healthcare agencies, ministries of health, product and service suppliers, industry consortia, patient access advocates, and global regions alike. Processes and systems geared at global reproducibility must be established with embedded efficiencies and high quality. Industry must ensure visibility for new products advancing to the clinical setting and market, with the sole purpose of reaching as many patients as possible. The revenue will come from patient numbers rather than high, targeted margins. Profitability, if done correctly, will naturally be achieved. Reimbursement models must be recognized to encourage wide adoption and sustained access.
From the perspective of a service provider, the bottlenecks attributed to CDMOs are important to address. For our space, that’s the traditional approach to process development and product life cycle. The resulting high costs, slow development, and capacity constraints lead to various barriers to patient access and a lack of reimbursement.
Taking a step back, therapeutic developers could (or should) focus on the entire value proposition of the therapeutic, in particular, therapeutic efficacy and getting it to patients. If the therapy works, it’ll be adopted. And therefore, financial milestones will be met.
Tackling the list of bottlenecks requires strategic and community partnerships and a global network, working together. This can drive costs down. This can provide developers with the tools they need, where they need them, with a focus on leveraging modular quality by design. (Quality and technology simplification make possible a formal shift from industrialization to operationalization. This creates practical processes and the use of systems built for realistically any clinician or operator, for the sake of global reproducibility.) This aligns missions and creates new opportunities in the therapeutic space. Efficient and affordable development and production are required to feed the total cost reduction necessary. This requires affordable production and clear distribution channels to help with the lack of reimbursement. And lastly, many industry players are talking about the problems with partial solutions in-hand. A total solution is needed now. All partners need to be vocal and demonstrate purpose. Products entering the clinic and market need to reach the patients.
Sustainability and affordability are inseparable. Broad adoption of therapeutics is only possible if they’re affordable, from development to the cost of the drug. One of the largest hurdles in cell and gene therapy, if not the biggest hurdle, is traditional or generalist CDMOs. The next generation service supplier is needed for next-generation therapies. If the root issue can be addressed, together with various partners listed, rare disease drug development can become sustainable. So, yes, there are keys to enabling this. But it all flows through manufacturing excellence and operations. From there, the right technologies and engineered improvements can be leveraged in a constructive way to have a paradigm-shifting impact on therapeutic development. This should give developers better access to funding and resources to make patient access possible and therefore, the development model, sustainable.
To achieve much of this required progress, knowledge and experience play a large role. This improves communication and transparency and how projects are handled from inception. We’d encourage all developers to work with good project management teams and teams of experts. Nothing adds to cost and time to develop like choosing the wrong partner for the task.
Aaron Dulgar-Tulloch, Ph.D., Vice President and Chief Technology Officer, Genomic Medicine, Cytiva
Rare diseases impact a small patient population, which provides little financial incentive for commercial drug development. To address such challenges, developers of drugs targeting rare diseases must focus on keeping development and approval costs as low as possible. To achieve this, here are several approaches to consider:
Academic/government collaboration and funding models are effective for early-stage innovation. They can facilitate the development of new modalities with public-private partnerships and funding. Such partnerships can serve as a springboard for broader adoption in collaboration with commercial partners.
Favorable commercial return approaches, such as providing an exclusivity period or reimbursement for a period, may be attractive to drug developers focused on recouping their R&D investment and addressing concerns regarding return on investment.
Simplified approval processes with regulators considering streamlined approval based on disease severity, patient population, and treatment risk may accelerate clinical development. These processes include faster reviews, early launches with follow-up data, and closer collaboration with developers, each intended to reduce costs and speed up market entry.
Leveraging artificial intelligence: AI offers promising tools for in silico molecular designing, predicting biological responses, and identifying patient profiles. When combined with platform-based approaches, AI may enrich data and improve forecasting for future therapies, reduce risk, and accelerate development.
Elisabeth Gardiner, Ph.D., Chief Scientific Officer, Tevard Biosciences
A sustainable path in rare disease drug development lies in platform-based therapeutics that target shared genetic mechanisms. Nonsense mutations, for example, are responsible for many genetic diseases, and tRNA-based therapies can restore protein function across multiple therapeutic indications. Basket trials, which group patients by molecular etiology rather than disease label, can further streamline access to targeted therapies.
Gene therapies, including AAV delivery, exon skipping, base editing, and gene replacement, offer scalable ways to correct mutations. Initiatives like the NIH’s Bespoke Gene Therapy Consortium (BGTC) are building shared vector libraries and manufacturing pathways, accelerating progress even for ultra-rare conditions.
Expanding access to genetic testing ensures timely diagnoses and trial enrollment. Patient stratification has enabled precision approaches in disorders like Angelman syndrome, Duchenne muscular dystrophy, and giant axonal neuropathy. Finally, sustainability depends on data sharing, AI integration, and adaptive regulatory frameworks to drive innovation and deliver therapies faster.
Judy Ashworth, M.D., Chief Medical Officer, Novadip
In order to encourage and sustain innovation, there are a multitude of stakeholders upon which companies like Novadip, that are dedicated to finding treatments for rare diseases, depend.
First and foremost, given the scarcity of patients, regulatory agencies need to be flexible and supportive with trial designs and the type and amount of confirmatory evidence needed to achieve market authorization. In addition, financial incentives, like the Priority Review Voucher program in the United States, as well as regulatory designations (e.g., Orphan Drug Designation) that extend market exclusivity are vital for companies to be able to generate positive business cases to attract investors. And, of course, the payers need to continue to be creative and supportive in the development of pricing models (e.g., value-based pricing, outcomes-based agreements) to sustain access and affordability.
Marc Hummersone, Ph.D., Senior Director of R&D, Astrea Bioseparations
Sustainability in rare disease drug development hinges on multi-stakeholder collaboration, innovative strategies, and supportive policies. Key elements include drug repurposing, which leverages existing safety data to accelerate development and reduce costs for ultra-rare conditions. Risk sharing through public-private partnerships and scaled incentives based on patient population size could help overcome financial and expertise barriers. Utilizing real-world data (RWD) enhances trial efficiency, market access, and evidence generation in small populations. Regulatory evolution, such as flexible frameworks and equitable access initiatives, addresses accessibility challenges in regions like South Africa through workshops and policy reforms. Fostering ecosystems with patient advocacy ensures priorities align with needs, while overcoming obstacles like limited resources and data scarcity. These approaches collectively promote viable, long-term investment in therapies for neglected rare diseases.
Oxana Iliach, Ph.D., Senior Director, Regulatory Strategy and Policy, Certara
Researching and developing new therapies for rare diseases is inherently difficult because of the small sample size, leaving 95% of rare diseases without an FDA-approved treatment. Biosimulation (i.e., the use of computational modeling to simulate how a drug will impact the human body) can address this challenge by modeling larger populations based on clinical data from the limited number of real-world patients, providing more evidence that a drug is effective and safe. By creating these virtual patients, researchers can also use biosimulation to model how the disease would progress without intervention, essentially creating synthetic control groups, which means more real-world patients receive the experimental treatment.
The complexity, variety, and fast pace of innovation in the rare disease drug development space necessitates a ‘sandbox’ approach to regulatory submissions and approvals. This method refers to a controlled, collaborative space where regulators, industry sponsors, patients, and academic experts can test and refine new methodologies in real time based on the disease etiology and type of treatment that is being developed. This regulatory approach, alongside biosimulation, will make rare disease drug development more efficient, sustainable, and regulatory-friendly. The latest example of regulatory innovation to increase sustainability of rare disease drug development is FDA RDEP, a new proposed process to facilitate the approval of drugs to treat rare diseases.
Matthew Weinberg, President, Regulatory Services, ProPharma
Making rare disease drug development sustainable requires efficiency, creativity, and collaboration. Patient populations are inherently small, requiring companies to design lean trials that maximize every data point. Adaptive trial designs, platform studies, and natural history data can reduce development timelines while strengthening scientific validity. Engaging patients and advocacy groups early helps identify meaningful endpoints and improve recruitment and retention, which is critical when eligible participants are limited. Building cross-sector partnerships with academia, research networks, and even competitors allows data sharing and avoids duplication of effort. Companies should also plan for sustainability beyond approval by considering life cycle management strategies, long-term safety data collection, and payer engagement to demonstrate value. Finally, integrating real-world evidence into both development and commercialization provides insights into long-term effectiveness and supports ongoing access. Taken together, these approaches enable companies to deliver innovative therapies for rare disease patients while maintaining scientific rigor and business viability.
Taehyeong Kim, Associate Director of Project Management, Samsung Biologics
The development path of rare disease drugs to market is resource-intensive and fraught with uncertainties. Drug developers are facing a twofold imperative: expedite the delivery of innovative therapies while ensuring that their pipelines remain commercially viable.
Sustainability in drug discovery hinges on balancing innovation with efficiency. Each rare disease program tends to address a small patient population, which can limit commercial returns. At the same time, regulators and patients still demand robust quality and efficacy. To reconcile these dynamics, developers are tasked to minimize risks, accelerate timelines, and optimize processes, without compromising the integrity of the science.
This is where an end-to-end integrated contract development and manufacturing organization (CDMO) becomes more than just an outsourcing vendor but also a strategic partner. A CDMO with end-to-end capabilities, from early process development through clinical and commercial manufacturing, can nurture the life cycle of a novel therapy with consistency, speed, and quality. By consolidating operations under one roof, developers avoid costly handoffs, mitigate delays, and maintain quality throughout scale-up.
The underlying value of partnering with an end-to-end CDMO extends beyond efficiency. A trusted, integrated partner can help anticipate regulatory needs, enable accelerated technology transfers, and ensure long-term supply reliability, critical factors in rare disease markets where every batch matters.
For companies venturing into rare disease innovation, choosing the right partner is a strategic commitment to both patient well-being and business sustainability. End-to-end integration offers a pragmatic path for making rare disease drug development a sustainable venture.
John Yu, M.D., Chief Executive Officer, Kairos Pharma
Sustainability in rare disease drug development requires addressing two core challenges: effectiveness over time and accessibility. One major hurdle is drug resistance, where treatments initially work but lose impact as the disease adapts. Companies tackling this issue are exploring ways to extend the effectiveness of therapies, ensuring patients benefit from lifesaving medication for longer periods. This not only improves outcomes but also maximizes the investment in research and development. From a manufacturing perspective, creating therapies that are scalable and adaptable also contributes to long-term sustainability. Developing treatments that can evolve alongside resistant disease strains allows for smoother integration into clinical practice and reduces the likelihood of therapies becoming obsolete and having to begin the whole drug development process over again. In rare diseases, where patient populations are small, every advancement must deliver meaningful, lasting value. By combining scientific innovation with input from patients and clinicians, companies can create therapies that remain viable, effective, and practical for both patients and healthcare systems. Ultimately, sustainability depends on making rare disease treatments not only innovative but also resilient over time, to allow for companies to streamline the whole manufacturing supply chain to make it both more sustainable and affordable.
David Fischer, Ph.D., Chief Technology Officer (Early Discovery), Charles River Laboratories
Sustainable rare disease drug development demands a hybrid approach that integrates human-relevant and animal models to optimize precision, scalability, and safety. Human-relevant models, especially patient-derived induced pluripotent stem cells (iPSCs), are now central to efficacy testing, offering disease-specific insights, especially for neurological and systemic conditions, and enabling personalized therapeutic approaches.
While human cell models are essential for evaluating targeted and personalized therapies, animal models remain indispensable for safety pharmacology, toxicology, and mechanistic studies. They help uncover dose-response relationships, delivery challenges, and potential toxicities, particularly in gene and CRISPR-based therapies. Recent regulatory shifts, such as the move toward one-species toxicology for ultra-rare oligonucleotide therapies, reflect growing confidence in hybrid data strategies.
To ensure sustainability, developers must invest in parallel validation frameworks: human cell models for precision and scalability, animal models for depth and safety. Industry-wide collaborations are expanding access to validated models for conditions like ALS, Huntington’s, and Duchenne muscular dystrophy, supporting more efficient and ethical development pipelines.
As rare disease programs become increasingly personalized and platform-based, sustainability will depend on adaptive testing frameworks, strategic model selection, and continued regulatory innovation that supports both scientific rigor and patient safety.
