The Science of Targeting Multiple Immune Components in ITP: Q&A with Dr. Srikanth Nagalla

Sometimes, new therapies require researchers to look at a condition from a new perspective.

Dr. Srikanth Nagalla, MD, MS, is the chief of benign hematology at Herbert Wertheim Cancer Institute, where he’s working on a new treatment paradigm for immune thrombocytopenia (ITP). According to him, the condition has traditionally been viewed as a platelet disorder.

However, he says when he looked at ITP from the patient experience, he viewed new ways to view its impacts. This includes persistent fatigue, emotional and cognitive health impacts, and reduced productivity.

He spoke with Pharmaceutical Executive about his research and new treatment approach, which he says goes beyond just symptom management. According to him, this has created new ways in which treatment is defined and measured.

Pharmaceutical Executive: How is the field reconciling the gap between clinical measurement and patient experience?
Dr. Srikanth Nagalla: There is growing recognition that traditional clinical endpoints do not always capture the full burden of immune-mediated diseases. In ITP, platelet count remains an essential measure of bleeding risk, but it does not always reflect how patients feel or function. Some patients continue to experience fatigue, cognitive difficulties, anxiety, and reduced quality of life even when platelet counts improve. As a result, clinical research and practice are increasingly incorporating validated patient-reported outcome measures alongside laboratory and disease activity endpoints. The goal is not to diminish the importance of platelet counts, but to develop a comprehensive measure of disease experience and control that reflects both clinical outcomes and the outcomes that matter to patients.

PE: What is required from a drug development standpoint to target several components of the immune system simultaneously?

Nagalla: From a drug-development standpoint, targeting several components of the immune system at once requires a very clear map of the disease biology, so you know which innate and adaptive pathways are driving pathology and which are downstream consequences. The goal is not broad immunosuppression; it is to rebalance immune signaling in a manner that engages multiple relevant pathways while preserving normal immune function. That also means incorporating translational biomarkers early in development to demonstrate target engagement and pathway modulation in preclinical models and then carry those insights into disease-specific clinical programs.

PE: What are the safety considerations when developing therapies that hit multiple parts of the immune system?

Nagalla: The primary safety consideration is achieving meaningful immune modulation without compromising normal immune function. Developers must carefully evaluate infection risk, cytopenias, thrombotic and bleeding events, and off-target effects in organs such as the liver and heart, while also understanding whether the therapy preserves normal immune-cell populations and physiologic functions. As with any immunomodulatory therapy, long-term studies remain essential to fully characterize safety across broader patient populations.

PE: How do you build clinical trial endpoints around symptoms such as fatigue or cognitive function?

Nagalla: Endpoints such as fatigue or cognitive function should be incorporated prospectively using validated patient-reported outcome instruments and functional assessments alongside traditional clinical measures. In ITP, there is increasing recognition that patients may continue to experience fatigue, psychomotor impairment, and a negative impact on their quality of life even when platelet counts improve, highlighting that laboratory values alone do not fully reflect disease burden.

PE: What benchmarks beyond platelet count should be measured for ITP?
Nagalla: Platelet count will always remain a fundamental measure in ITP because it reflects bleeding risk, but it is increasingly viewed as only one component of disease control. Other important benchmarks include bleeding events, need for rescue medication, durability of platelet response, physical fatigue, health-related quality of life, and patient-reported measures of daily functioning and emotional well-being. As our understanding of ITP has evolved from a disorder defined primarily by thrombocytopenia to one driven by complex immune dysregulation, these broader measures provide a more complete assessment of whether treatment is meaningfully improving patients' lives.