What Really Moves The Needle In Primary Immunodeficiency Research And Treatment

By Nisha Jain, vice president of global clinical development and strategy, Kedrion Biopharma

Those working on clinical trials in rare disease know the journey is rarely straightforward. Primary immunodeficiency (PI) is a perfect example. It’s a condition that doesn’t just challenge patients and clinicians but also those designing and running the studies that bring new therapies to life. With more than 450 genetic disorders under the PI umbrella, and symptoms that can masquerade as anything from allergies to chronic fatigue, it’s no wonder that both diagnosis and research can feel like solving a puzzle with missing pieces.

For clinical trials professionals, the stakes are high. Every patient enrolled represents not just a data point but a person who’s often spent years searching for answers. The diagnostic odyssey for PI can stretch over a decade, and that delay ripples into every aspect of clinical research: from identifying eligible participants to selecting endpoints that truly represent meaningful results. Part of the challenge of continuing to innovate in this space is to find smarter, more patient-centered ways to move research forward so that new therapies reach the people who need them, faster.

Designing Trials Rare Disease Realities

Running a clinical trial in PI encompasses understanding patients’ experiences and the practical realities of rare disease research. The diversity of PI in terms of how it looks, feels, and progresses means there’s no such thing as a standard approach. There are many challenges of designing a trial for diseases that affect around one in 1,200 individuals, many unknowingly. Some of the greatest hurdles include:

• Finding the Right Patients: With PI’s subtle and overlapping symptoms, identifying eligible participants can feel like searching for a needle in a haystack. Building relationships with advocacy groups, leveraging patient registries, and using real-world data have all helped us ensure our trials reflect the true diversity of the PI community.
• Choosing Endpoints That Matter: For PI, endpoints such as the rate of serious bacterial infections are meaningful measures of how a therapy changes lives. Aligning our trial goals with what matters most to patients and regulators has been key.
• Embracing Flexibility: No two PI patients are exactly alike, and our protocols need to reflect this individuality. Whether it’s allowing for different infusion rates or accommodating comorbidities and lifestyle factors, adaptive designs and subgroup analyses have helped us capture the nuances that make each patient’s journey unique.
• Prioritizing Safety: Rare disease patients often have complex medical histories. Proactive safety monitoring and transparent communication about risks are best practices and essential for building trust with both patients and the broader clinical community.

QIVIGY: A Case Study In Patient-Centered Clinical Research

The recent FDA approval of QIVIGY (immune globulin intravenous, human – IFAS 10%) is a testament to what’s possible when clinical trials are designed with patients at the center. Throughout development, our team made intentional choices grounded in patient feedback and practical realities. For instance, we permitted higher infusion rates in the trial, which shortened infusion times and made participation less disruptive for patients’ daily lives. This was an adjustment that proved important for enrollment and retention. In designing the study, we focused on the absence of serious bacterial infections as our primary endpoint, reflecting a clinical outcome that is both meaningful to patients and aligned with regulatory expectations. We also prioritized enrolling a diverse group of participants, aiming to capture a range of ages, backgrounds, and disease severities so that our findings would apply broadly across the PI community.

Beyond the clinical data, we considered real-world challenges like supply chain stability early in the process, recognizing how critical consistent access is for rare disease therapies. Together, these decisions offer a practical framework for how clinical trials in rare diseases can be more responsive to patient needs while still meeting scientific and regulatory standards.

4 Factors To Make Rare Disease Trials Better

QIVIGY’s journey to approval has reinforced some important truths:

1. Engaging with regulators from the beginning helps align trial design with approval pathways and patient needs.
2. Using technology can make recruitment smarter and more inclusive, especially when the patient population is as tight as it is with something like PI.
3. Working with advocacy groups, clinicians, and patients leads to better-designed trials and more meaningful results.
4. Planning for access, supply, and real-world implementation needs to be part of every clinical development strategy.

As demand for immunoglobulin therapies grows and the rare disease landscape evolves, lessons learned from QIVIGY about flexibility, patient engagement, and forward-thinking trial design are shaping the future of rare disease research. By expanding the clinical trial toolbox and keeping patients at the heart of the work, we can help ensure that every person with PI has access to timely, effective, and personalized care.

About The Author:

Nisha Jain is the vice president of global clinical development and strategy at Kedrion Biopharma, a biopharmaceutical company that collects and fractionates blood plasma to produce and distribute plasma-derived therapies worldwide for use in treating and preventing rare and debilitating conditions.