The rare disease ecosystem demands a fundamentally different approach compared to traditional drug development and commercialization. Many companies have struggled in this space because they failed to adapt their models, applying conventional strategies that don’t fit the unique challenges of rare diseases. Success in rare disease requires an integrated approach, where development and commercialization are seamlessly connected, with patient access and partnerships as the primary focus from day one. Unlike broader indications, there is no clear boundary between development and commercialization—commercial success is built early by placing patient access at the core of the strategy.

Ahead of Rare Disease Day 2025, we spoke with Joris Pezzini, Executive Vice President of Biopharma at Alira Health, to explore how biotech companies can successfully implement this integrated approach in rare diseases.

Why does the rare disease space require a fundamentally different approach compared to drug development and commercialization in broader therapeutic areas?

For decades, the pharmaceutical industry has been structured around the blockbuster model—targeting indications with millions of patients and developing treatments designed for broad populations. This large-scale approach shaped every aspect of the ecosystem, from research and development to manufacturing and commercialization, optimized for efficiency at scale.

In recent years, medicine has become more patient-centric, with targeted therapies focusing on specific subpopulations to achieve better efficacy and safety profiles. While many pharma companies have adapted to this shift, rare diseases push the boundaries of this evolving model, taking the principles of personalized medicine even further. In fact, these diseases have now reached the point where the traditional model is no longer feasible for development and commercialization.

Every cog in the pharmaceutical machine—development, production, commercialization—was built for scale. Applying this framework to rare diseases is like trying to fly a jumbo jet at low speed just above the ground; the system simply isn’t designed for it.

Successfully addressing rare diseases requires a complete redesign of the approach:

• Scale: An oversized infrastructure cannot efficiently support small patient populations.
• Economics: Traditional development models often make the business case unviable.
• Engagement: Direct collaboration with patients is not just beneficial—it’s essential for both development and commercialization.

Rare disease innovation demands a tailored model that prioritizes agility, efficiency, and deep patient involvement. Only by reshaping the entire ecosystem can we unlock meaningful progress for these underserved communities.

What are the risks of applying conventional pharma strategies to rare disease, and how can companies avoid these pitfalls?

In rare diseases, the risks associated with drug development are often much more binary than in broader indications. By this, I mean that one failure can have a catastrophic impact on a program, leading to its rapid termination. While failures can also occur in more traditional indications, there is often more flexibility—companies can sometimes mitigate errors, and the program may still provide value to patients, albeit less than anticipated. In the rare disease space, however, any misstep in the development process can quickly derail the entire program.

Also, a traditional development plan for a rare disease treatment is not cost-effective and impactful enough to make a positive business case and secure funding. Investors simply won’t back the program, effectively ending the project.

Another risk lies in the clinical trial. Designing a trial without regard for patient locations or the emotional connection they have with their disease can cause major recruitment challenges, likely leading to early termination of the program. Also, incorrectly identifying the appropriate comparator or failing to leverage historical data to clearly demonstrate efficacy can result in clinical failure.

Finally, failing to anticipate commercial needs early in development can lead to either under- or over-investment in commercial infrastructure, creating a disconnect with patients and their communities, which may result in significant underperformance or, in the worst case, the program’s halt.

In rare diseases, the typical risks are magnified, and a single failure at any point can disrupt the entire pathway. Careful, strategic planning is essential at every stage, and involving patients, who are the only ones able to foresee potential challenges, in that planning is vital. Because rare diseases are not widely understood or described, patients’ insights are crucial for identifying risks early.

Since there’s no clear boundary between development and commercialization in rare diseases, how should companies redefine success throughout the process?

I actually think it’s easier to assess the potential for successful commercialization in rare diseases than in broader indications. Simply put, because the development and clinical trial environment closely mirrors the commercial conditions, you can gauge future success more directly through the progress in your program. In many cases, the number of patients in your clinical trial represents a significant portion of the entire patient population for that disease. The percentage of patients in the trial often corresponds to a high proportion of those who will eventually be treated during commercialization, making the link between development and commercialization very clear and reliable.

For example, if recruitment is progressing smoothly in your clinical trial, if patients are staying on protocol as expected, if you’ve identified the right centers and principal investigators in each country to drive recruitment, and if you’re collaborating with the right patient associations—these are all strong indicators of successful future commercialization. Additionally, if patients in the trial easily understand the medical value of your drug or device, that further strengthens  confidence in your ability to succeed commercially.

Ultimately, success in rare diseases isn’t just about regulatory approval—it’s about ensuring patients can access and benefit from the treatment. Companies that integrate patient needs into every stage of development and commercialization will truly make an impact.