Redefining Rare Disease Clinical Research: Inside Takeda’s Patient-Centered, Tech-Driven Approach

Patient-centered innovation and technology are reshaping rare disease clinical research.

With small patient populations, limited data and high unmet needs, success in rare disease clinical research often depends on collaboration and creativity across multiple fronts.

Researchers must balance scientific rigor with ethical responsibility, designing studies that are both feasible and meaningful for patients.

Building trust within rare disease communities and incorporating their voices early in development are now essential steps toward achieving equitable and impactful outcomes.

In this Xtalks Clinical Edge™ interview, Mike Denne, PharmD, Vice President of US Medical Affairs for Rare Disease and Plasma-Derived Therapies at Takeda, discusses how the field is evolving, from incorporating patient perspectives earlier in development to leveraging real-world evidence (RWE) and AI to reshape the way trials are designed and conducted.

Xtalks Clinical Edge: Issue 6 — Redefining Rare Disease Clinical Research: Inside Takeda’s Patient-Centered, Tech-Driven Approach

Xtalks Clinical Edge™ is a magazine for clinical research professionals and all who want to be informed about the latest trends and happenings in clinical trials. This magazine immerses you in a world where industry leaders, patient advocates and top researchers converge to provide the most insightful perspectives on clinical trials.

Designing Feasible, Inclusive, Patient-Centered Rare Disease Trials

Patient centricity is an important facet in clinical research today. However, it’s important to implement it strategically and authentically. Beyond being a regulatory checkbox or a marketing slogan, robust, organic integration of patient perspectives must be embedded throughout the trial lifecycle, from study design and recruitment to data interpretation and post-trial engagement.

Patient centricity ensures studies are designed around patients’ needs, preferences and daily realities, in addition to scientific and regulatory priorities. Importantly, it helps identify what patients are looking for in a trial and the things most important to them with respect to access, participation and improvement measures.

By involving patients early and meaningfully, trials become more inclusive and focused on outcomes that truly matter to those living with disease. Ultimately, this approach builds trust, improves data relevance and accelerates the development of therapies that deliver genuine value to patients and society.

It also improves trial feasibility and relevance to also build lasting trust between sponsors, investigators and the communities they aim to serve, creating strong networks and research ecosystems.

Dr. Denne emphasizes that engaging patients and advocacy groups early in the process helps researchers better understand disease experiences and trial expectations. The key is to get input early and from diverse sources.

“We’re always trying to make sure that we have the patient’s voice, the community’s voice, whether that’s researchers and advocacy groups, included in how we’re designing trials,” he explains. In some rare diseases, advocacy infrastructure is well established, while in others, researchers must find alternative ways to gather patient insights.

He also describes how teams actively partner with institutions that serve underserved or underrepresented communities, particularly when a study aims to target a diverse participant population. This outreach, he emphasizes, must be intentional and hands-on.

This helps improve the diversity of trials, not merely for the purposes of checking a box, but by understanding and addressing local needs.

Local site development is also an essential part of improving access and diversity in clinical studies. Building relationships with investigators and clinicians within underrepresented communities helps expand participation and ensure trials reflect real-world populations.

Navigating the Unique Challenges of Rare Disease Research

The rare disease space brings a unique set of challenges, smaller patient populations, heterogeneous symptoms and complex biology that make traditional trial models sometimes difficult to apply.

Ethical considerations are also paramount in rare disease trials, where withholding treatment or assigning placebo arms can be controversial. Dr. Denne acknowledges that decisions around control groups are rarely straightforward and often depend on multiple layers of input, from regulators and data safety boards to clinicians and patients themselves.

No two situations are ever the same, and there’s no one stakeholder who decides what’s ethical; it’s always a collective process with multiple approaches.

“We’ll often pick the leading approach, taking into account various factors and getting input from the regulatory bodies around the globe as to how they feel about a particular study design before we finalize the protocol,” explains Dr. Denne.

He adds that emerging data science tools are beginning to change the approach. With advances in generative and agentic AI, researchers can build synthetic control arms from existing datasets, reducing reliance on placebos and potentially speeding up access to treatments.

Building reliable controls without placebo arms in rare diseases is becoming more feasible, but regulators are still determining how to evaluate such approaches.

Aligning Science and Patient Needs in Medical Affairs

Medical teams play an integral role throughout the entire drug development journey, from the moment a drug is conceived to its approval, commercialization and later lifecycle stages. It sits at the intersection of science, clinical care and patient advocacy.

Dr. Denne says it’s an exciting time to be in medical affairs.

“We’re in touch with the scientific community, the clinical community and with advocacy organizations,” he explains. “That means we understand the entire patient journey, what’s impacting patients most and what they’re really looking for from their treatments.”

Medical affairs teams work closely with R&D from the very beginning, even at the stage of defining a target product profile. This early collaboration helps ensure that development plans align with patient needs and real-world priorities. And as programs move through Phases I, II and III, that influence extends further, encompassing considerations around patient access, equity and study design feasibility.

“It’s not enough to get a product approved,” says Dr. Denne. “We also have to make sure patients who need it can access it.”

Once a therapy reaches the market, medical affairs continues to generate RWE to fill in the gaps left by clinical trials, exploring how a treatment performs in diverse populations and in everyday settings.

This evidence generation doesn’t stop after approval; it evolves as science and treatment paradigms change, addressing new questions and opportunities such as combination therapies or personalized approaches.

Building a Global, Trust-Based Ecosystem

Rare disease research is increasingly global, but local realities, from healthcare infrastructure to cultural and geopolitical factors, often shape what is possible. Dr. Denne explains that trial design must account for these variations while still aiming for data that can support global access.

“You want to design studies that answer globally relevant questions,” he says, “but also consider standards of care and what’s practical and appropriate in specific regions.”

That balance, he adds, is central to improving equitable access to therapies across geographies.

Dr. Denne says that Takeda’s longstanding global presence helps foster connections with different stakeholders, helping his team to understand where the greatest unmet needs are and how to deliver medicines to those places by engaging with stakeholders in a diverse way.

“I think some of the things that might be unique to Takeda that give us a really good edge, and maybe particularly in rare diseases, is that we’ve been working in rare disease for decades and building trust in relationships with the rare disease communities.”

He reflects that, “as a result, sometimes we can even reactively learn things without even reaching out because we have this great two-way communication going with the rare disease communities. They’re not shy in telling us if we’re doing something that’s not exactly the way they would want it or if there’s something that they’d like to see us explore that we’re not exploring.”

None of this is possible without collaboration. From patient advocacy groups to clinicians and scientists, medical affairs serves as a central connector between all stakeholders in the drug development ecosystem.

“The inclusion of the patient voice has evolved tremendously in the past decade,” says Dr. Denne. “It’s not just medical affairs, R&D and even regulatory bodies are now engaging directly with patients and caregivers to shape better decisions.”

Equally important is the global scale of that engagement. Takeda’s international footprint allows it to work with patients and investigators across geographies and cultures, fostering diversity and ensuring that insights reflect the realities of different populations. “Some of this work has to happen at the local level,” he explains.

RWE and Evolving Data Strategies

RWE has become a valuable complement to traditional clinical data, particularly in rare diseases where trial populations are limited. Dr. Denne notes that RWE can not only inform trial design but also support regulatory submissions and label updates.

He points to Takeda’s von Willebrand factor replacement therapy as an example of how clinical and real-world data (RWD) were combined to expand the therapy’s label. RWE helped fill data gaps for subtypes not well represented in initial trials, he explains, showcasing a growing role for RWD in bridging evidence gaps and supporting broader regulatory decisions.

Regulators, especially the FDA, are also rethinking how they evaluate treatments for rare conditions. Dr. Denne says there is growing openness to using surrogate endpoints, accelerated approvals and platform-based development, all of which can help reduce timelines and bring therapies to patients faster.

At the same time, he cautions that this evolving environment requires careful scientific and ethical stewardship. “There’s a lot of innovation happening,” he says, “but also a responsibility to make sure we’re advancing the most meaningful and transformative ideas.”

AI and the Future of Clinical Research

Dr. Denne believes technology, particularly AI, will continue to transform trial design and execution. Predictive models could one day help researchers refine study parameters and enrollment in real time, improving both speed and precision.

The future of rare disease research lies at the intersection of patient insight, ethical trial design and data-driven innovation. Progress in the space depends not only on new technologies but also on a commitment to collaboration and building trust across all stakeholders, from researchers and regulators to patients and their families.

He explains that Takeda consults multiple expert groups when designing studies, including data safety specialists, clinicians treating the condition and, importantly, patients themselves. All of these perspectives help determine the most ethical study design.

For instance, in bleeding disorder research, a key question is whether it’s appropriate to compare a prophylaxis arm with one where treatment is only given after a bleeding event.

Technology will also be a powerful driver in trial design.

Dr. Denne notes that technology is transforming how control groups are built. With advances in generative and agentic AI, researchers can now create synthetic control arms using existing data or even adjust enrollment dynamically based on participants already in the study. This makes it increasingly possible to conduct rigorous, well-controlled rare disease trials without relying on traditional placebo arms, though regulatory acceptance still varies case by case.

Its predictive capabilities can help identify optimal trial designs and even adapt enrollment strategies in real time, creating a far more dynamic research environment.

The result, he notes, will be studies that are as rigorous, or better, while being completed more efficiently and getting treatments to patients sooner.

Looking ahead, he predicts that in a decade the industry will look back and recognize just how transformative these technological advancements have been for drug development.

“Maximizing what technology can do for us in drug development is going to be key. In 10 years, we’ll look back at what we’ve been doing prior to now and think, wow, we’ve come a long way. That is a major prediction I have.”