Rare Disease Day 2026: Accelerating Rare Disease Drug Development Through Cross-Functional Innovation

We asked our experts how their work is driving innovation and advancing rare disease treatments. Here's what they had to say. From your expertise in regulatory strategy, what do you see as the biggest challenges and opportunities in regulatory environment for rare diseases, and how can innovative approaches help address these challenges and leverage opportunities? There are multiple challenges and opportunities in the regulatory environment for rare diseases. In the interest of time, I want to focus on two major challenges, diversity of treatment that are being developed and imbalance in the treatment development. I intentionally using word of treatment because it implies to drugs, biologics, combinations products, and so on so. So those challenges, by the way, are also creating a lot of opportunities that I would like to discuss. Let's talk about diversity of treatments for rare diseases. The landscape of rare disease drug development is enormous, and the range of treatment developments is huge. On one end of this range is repurposing of the drugs that are already approved and are often approved for the treatment of common disease and as such, have a proven safety and efficacy profile, at least for one indication. But on the opposite end of this development range is individual gene cell therapy treatments that could be developed for individual patients and will have unknown safety and efficacy profile. So and as I mentioned, the other challenge is imbalance in treatment development. Meaning, there is a pipeline of drugs being developed for some rare diseases such as rare cancers or neurological diseases. And for some other rare diseases, for example, mixed connective tissue diseases or autoimmune lymphoproliferative symptoms, there are very limited development. So those two major challenges, the diversity of treatment development and imbalance in treatment development, are also present opportunities. And I'm afraid I will not be able to provide one size fields all solutions. However, in my opinion, the way to expedite and find the solutions to these challenges could be first by increasing collaborative efforts of different stakeholders, such as patients groups, health care providers, researchers, companies, and regulators. We already see this happening, but this should start happening on the international level across different jurisdictions. And I would like to see regulators working collaboratively in developing a regulatory alliance approach to development and approval of treatments for rare diseases globally. So the company doesn't duplicate the efforts and save time from going from one jurisdictions to another. And then the second solutions is in interpretations of innovative approaches in development. For example, including of nontraditional approaches to selections of biomarker biomarkers and endpoints, leveraging of modeling and bio simulations to accelerate drug development, increased collaborations between the regulatory agencies and health technology assessment agencies. And for my personal experience, I was fortunate to work in the area of rare diseases for almost ten years. I've been volunteering at Canadian organizations for rare diseases and for also at the International Rare Disease Research Consortium. And I've been supporting multiple developments of drug for rare diseases. And I can tell you that in the last two, three years, the development is really, really growing, which is fantastic. For example, just last year, our Sertara teams of regulatory strategy provided regulatory strategy support for almost fifteen treatments development. And, it's really enjoyable to see how the progress is being made in the development and how those development are expediting. So and I'm really hoping that this trend will continue.

We asked our experts how their work is driving innovation and advancing rare disease treatments. Here's what they had to say. How does your work with regulatory submissions impact the development of rare disease therapies, and what changes have you seen in the development of rare disease therapies? Hello, I'd like to start with a little context for rare diseases. FDA's core definition of a rare disease is any condition that affects fewer than two hundred thousand people in the US, which is less than one percent of the population. It's estimated that there are as many as ten thousand different rare diseases, but only about five percent of those have an FDA approved treatment. Interestingly, the majority of rare diseases are genetic central nervous system disorders that are neurodegenerative and produce debilitating and often fatal muscle problems. I've been working in drug development for more than thirty years. During that time, I've had the opportunity to play a key role in the development and approval of many products, including some of which you may be familiar, such as Nexium. Unfortunately, for much of my career, companies would not pursue treatments for rare diseases due to the small number of individuals with each rare disease and the difficulty defining the development program needed to gain approval. I remember talking with a father whose son had Friedreich's ataxia, a rare inherited neurodegenerative disorder that primarily affects the central nervous system and leads to impaired muscle control. Only about five thousand people in the US have this condition at any one time. This father's young son required a wheelchair and had a life expectancy of only about thirty five years, yet no treatments existed and no companies were pursuing a treatment for it. Because of this, he had started a patient group for the disease and was lobbying pharmaceutical companies to take on the search and development of possible treatments. Thankfully, drug development and the regulatory environment have changed dramatically over the past two decades to better support development of drugs for rare diseases and there are now hundreds of programs ongoing across dozens of rare diseases. With that said, developing a treatment for a rare disease is still an extremely difficult task. From a development standpoint, one of the biggest challenges is identifying gaining regulatory authority agreement on how best to measure the treatment's effect of the on the patient's unmet medical need. From the perspective of how we write up and present it to the regulatory authorities, the very small number of patients available for study is the biggest difficulty. Specifically, that requires presenting results by each individual patient rather than using statistical tests or averages across a large number of patients. I'm very proud to have had a lead or support role on a number of rare disease marketing applications over the years for products that then got approved and made a difference in those patients' lives. I'm even more proud that our Certara regulatory writing team has now supported more than one hundred and ten rare disease submissions, covering more than seventy unique rare diseases. It's amazing to be a part of supporting those programs and especially gratifying to see ones we've supported prove effective in helping these patients and get approved for use. In fact, just last year, eleven of the marketing applications we've supported for rare diseases were approved across the US, Europe, and Japan. I hope you'll join us in celebrating Rare Disease Day on February twenty eighth as we continue efforts to address the unmet medical needs of the people suffering from these rare conditions. Thank you.

We asked our experts how their work is driving innovation and advancing rare disease treatments. Here's what they had to say. Do you see as the biggest challenges and opportunities in advancing gene therapy in rare diseases, and how can innovative approaches in the field help address these challenges? Gene therapy is finally starting to deliver on its potential. After decades of talk about the promise of gene therapy, but little tangible progress, we are now actually seeing novel treatments reaching patients. Rare diseases are at the forefront of this and illustrate the transformative potential of gene therapy. We have examples of diseases that were literally death sentences but now can, for the first time, be managed if not cured. The expectation is that treatments for more and more rare diseases will emerge. And while the scientific challenges shouldn't be underestimated, the biggest hurdle I see is financial. Healthcare systems don't have unlimited resources, and not every new treatment can be funded. The challenge, therefore, is how to bring down the costs of development of gene therapies so that companies don't have to charge huge prices in order to make a new medicine commercially viable for small populations. This is where innovative approaches are key. For example, using computer modelling and simulation methods to streamline clinical development. This can help significantly reduce the cost and time to run clinical studies. It is even possible to extrapolate information from other sources to avoid having to run some studies at all. We hope that by working with companies in this way, we could help make future gene therapies for rare diseases more affordable and thereby more accessible.

We asked our experts how their work is driving innovation and advancing rare disease treatments. Here's what they had to say. What is the role of biosimulation in the development of rare disease therapeutics? There are several challenges specific to drug development for rare diseases that require innovative solutions and technology. By definition, the number of patients with the disease, and therefore, the number of participants in a clinical trial, is very low. Sometimes literally only a few individuals. So the interpretation of such trials cannot rely on conventional statistical approaches, also because the variability in response between patients can be very pronounced. In addition, it is often not possible to include a placebo group in the trial. And finally, treatments for rare diseases often involve innovative novel modalities such as gene therapy for which there are no conventional translational approaches available to, for example, define a first in human starting dose. Now this is where biosimulation or quantitative system pharmacology, QSB, comes in. And this is illustrated very nicely in a recent paper we published in Clinical Pharmacology and Therapeutics with Sanofi on the development of a so called virtual or digital twin model for Pompe disease. Pompe disease is a rare genetic condition in which a complex sugar called glycogen builds up in the body cell due to lack of a specific enzyme called GAA. It causes severe muscle weakness and the disease can be fatal. With our partners at Sanofi, we developed a QST model, which allowed us to not only replicate actual clinical trial data, but more importantly, also to simulate new trials for untested scenario, such as new dosing regimens, which have not been tested in actual clinical studies yet. In such virtual trials, we can, of course, generate many more patients than we can study in real life, which allows us to explore much better, for example, the question why individuals response differently and how we can personalize treatments. Indeed, with our model, we can create a so called virtual twin on the computer for each actual patient, which allows us to optimize dose and treatments for each individual in the best possible manner. There is also increasing interest to use this technology to replace or complement placebo groups in clinical trials in rare diseases, where each patient receives treatments and its virtual twin acts as the placebo control.

We asked our experts how their work is driving innovation and advancing rare disease treatments here's what they had to say: How has the regulatory acceptance of computer simulations evolved, and is there a standardised framework for these submissions? We have moved beyond using modern informed drug development, or MIDD, as a mere supportive sidecar. It is now a primary quantitative framework. The finalisation of the ICH M15 guidance is a significant milestone. This provides the global harmonisation we have needed, standardising the principles for model development, validation and reporting across different regulatory regions. It reduces the regulatory risk of using predictive models by ensuring that a model validated in one region meets the evidentiary standards of another. This should accelerate global filing timelines. Beyond general PKPD, which specific modelling architectures are effectively replacing traditional paediatric trials? In paediatrics we are leveraging several specific pillars to bypass the small adult fallacy. Mechanistic PBPK models these integrate age dependent physiological changes like organ maturation and enzyme ontogeny to refine dose selection through knowledge based extrapolation rather than simple allometric scaling. Quantitative systems pharmacology, QSP, can be used to extend PBBK frameworks by integrating the pharmacodynamic impact on tissues and organs. Population PK or POP PK is crucial for quantifying inter individual variability in sparse data environments, allowing us to identify covariates that actually drive clinical outcomes in And lastly disease progression and digital twins. By modelling the natural history of a rare disease we can create in silico comparators. This allows us to reduce or occasionally eliminate placebo arms by comparing treated patients against simulated disease trajectories. Beyond these models, there are some exciting AI machine learning paradigms on the horizon. Ultimately, how does this quantitative approach change the patient experience in rare disease research? The impact is clinical, but also deeply ethical. Over fifty percent of rare diseases affect paediatric populations. MIDD allows us to maximise the informativeness of every single data point. By using model based extrapolation we minimise invasive procedures, reduce the number of blood draws and limit the number of children exposed to sub therapeutic doses or placebos. We aren't just making trials smaller but we are increasing the statistical certainty and ethical rigour. MIDD isn't just a tool, it's the bridge between data scarcity and clinical certainty.

We asked our experts how their work is driving innovation and advancing rare disease treatments. Here's what they had to say. What are the main opportunities for using real world evidence to support regulatory decision making and market access for rare disease therapies? I'll speak briefly today about the opportunities for use of real world evidence, or RWE to support regulatory decision making and market access for rare disease therapies. And from a real world evidence perspective, rare diseases are unique in that they often lack a standard diagnosis definition, which makes the analysis of heterogeneous real world data sources and development of RWE from them challenging. I think reducing barriers to development and use of RWE in rare diseases is is critical because RWE presents a major opportunity to improve research by supporting regulatory approval and market access of therapeutics for new drugs. I think these opportunities loosely fall into three major baskets, integrating real world evidence into model informed drug development, fostering greater acceptance by stakeholders, and using advanced analytics to speed throughput and and processing. First, think that RWE has largely unrealized potential to date, to inform model informed drug development approaches. Early predictions of comparative effectiveness, generation of external or synthetic control arms to supplement data from randomized controlled trials, or integrating RWE into classical PK and pharmacometrics models, all can complement available gold standard RCT evidence to support regulatory and payer decision making. Second, from both the FDA and EMA are devoting time to better framing workflows for acceptance and integration of RWE into standard approval processes. And furthermore, the joint clinical assessment or JCA in the EU offers another high profile framework for which consideration and integration of RWE is is essential for success with payers. Finally, machine learning methods and judicious application of generative AI tools can help identify and extract more meaningful insights from small heterogeneous datasets in emerging rare disease indications like chimeric antigen t cell receptor therapy, more rapidly than can be done with traditional methods. So overall, I think, in light of all of these factors, RWE offers a substantial opportunity to improve rare disease research, drug approvals, and patient care, and I'm personally looking forward to Sartara's involvement in making these opportunities a reality.

We asked our experts how their work is driving innovation and advancing rare disease treatments. Here's what they had to say. CMC plays a critical role in ensuring the safety, quality, and scalability of rare disease therapies. How does Certara's expertise in CMC strategy help biopharma companies navigate regulatory and manufacturing challenges and accelerate the development of life changing treatments for rare disease patients? New drug approvals in rare disease field are on the rise, which is great news for the patients. Because of the high unmet need and lack of effective therapies, global regulatory agencies are assigning accelerated or expedited regulatory pathway for these therapies. While it is a welcome and necessary step for the benefit of the patients, it does bring more pressure on CMC to deliver the product in a shortened time frame while maintaining the same quality standards as expected for traditional therapies. To add further to the complexity, rare disease therapies cover a diverse set of modalities and delivery systems for small molecules, monoclonals, oligos, siRNA, cell and gene therapies, all of which require specialized manufacturing processes. Smaller patient population can lead to slow recruitment requiring agile manufacturing approach for delivering clinical supplies. It also requires the ability to manufacture both clinical and commercial supplies with limited amounts in smaller batch size with quality by design built in. You also need a streamlined supply chain approach targeted for the small fraction of patient populations spread across diverse geographies. So in terms of the CMC strategy to tackle these challenges, first step is to fully understand the molecule you are working on and the ideal product requirements for the target patient population. This will help you select a face appropriate API and formulation strategy with the ability to quickly transition into late stage clinical and commercial manufacturing. An early development team of cross functional experts can go a long way in developing this understanding. In silico modeling tools can also help further to assess the impact on product performance as a result of these formulation or manufacturing changes which are bound to happen during development of these products. One also needs to identify appropriate CDMOs and develop a strong working relationship and understanding with those CDMOs so that they can adapt to on demand manufacturing strategy to deliver the needed clinical or commercial supplies in a flexible and agile manner. Finally, an early and data driven dialogue with regulatory agencies will also go a long way in assessing if you're on the right track for your CMC strategy. The agencies understand the complexities associated with accelerated pathways and are developing guidances and programs to help sponsors overcome these challenges. So in conclusion, a deep understanding of your product, patient unmet needs, and a collaborative approach can go a long way in developing a quality product or in delivering a quality product in a timely manner. Thank you.

We asked our experts how their work is driving innovation and advancing rare disease treatments. Here's what they had to say. Over the years, I have had the opportunity to work with teams on blockbuster drugs, drugs for rare CNS disorders, and drugs for neglected tropical diseases such as malaria, onchosercosis, and sleeping sickness, among others. Each new drug product required the best multidisciplinary interactions as a team to achieve a successful new product. The development process, in my experience, was accelerated in each and every instance by model informed drug development principles to ensure that, as a function of dose, we were delivering the right concentration of active drug for the right amount of time to the appropriate target, no matter who the patient is. Developing new drugs or biologics for neglected tropical diseases that may be rare in higher income countries, but common in regions with resource limitations, means that we have to unite to meet the challenges that arise as a function of global health resource disparities. Despite these disparities, we can celebrate success stories of teams that have persevered and overcome these disparities. One example of a successful new product is moxidectin, which has been approved for the treatment of onchocercosis, otherwise known as river blindness, by the US FDA, and more recently, has received approval by the Ghana Food and Drugs Authority for the treatment of river blindness in adults and children aged four years and older. This approval precedes the use of moxiductin for community based mass drug administration in regions endemic for river blindness. According to Mark Sullivan, the managing director of medicines development for global health, Moxiductin is a great example of the reason that MDGH exists, to bring life changing new medicines to communities affected by neglected diseases where market driven models have failed. There are other examples of public private partnerships that unite talented individuals across the globe to leverage the best of drug development science to bring new products to treat and potentially eliminate neglected tropical diseases. Just recently, the World Health Organization announced that Guinea has eliminated human African trypanosomiasis, otherwise known as sleeping sickness, as a public health problem. Drugs for Neglected Disease Initiative, DNDI, which is a public private partnership, has been at the forefront of developing new treatments for sleeping sickness, leveraging the best science for the most neglected. Although the successful development of a blockbuster drug can be financially rewarding for the investors, there is a different sense of reward as new products for global health have an impact on lives of those suffering with neglected tropical diseases. And so we do our best to leverage our best in this process.