Hereditary Angioedema: Unlocking Earlier Diagnosis

Leveraging Quest Diagnostics Data and Prognos Health Algorithms

Hereditary angioedema (HAE) is a rare and debilitating genetic condition affecting an estimated 1 in 50,000 individuals. Characterized by unpredictable, recurrent episodes of painful and sometimes life-threatening swelling in various body parts, including the airway, HAE presents a significant burden of disease. A key aspect of this burden lies in the underdiagnosis that plagues the HAE community. Many individuals endure years of debilitating symptoms, often misdiagnosed with more common conditions, leading to a reported average time to diagnosis of 7-10 years. This diagnostic odyssey not only impacts patients' quality of life but also delays access to effective therapies.

The landscape of HAE treatment has been rapidly evolving, with the development of several targeted therapies for both acute attacks and prophylaxis. These include C1INH concentrates (Cinryze, Haegarda, Berinert), recombinant C1INH (Ruconest), the bradykinin B2 receptor antagonist icatibant (Firazyr), and the plasma kallikrein inhibitor ecallantide (Kalbitor). The availability of these life-changing therapies underscores the critical need for timely and accurate diagnosis to ensure patients receive the best possible care. Commercial teams play a pivotal role in bridging this gap, ensuring access to these essential treatments.

The Diagnostic Labyrinth of HAE

Diagnosing HAE remains a complex undertaking. Its symptoms can mimic other forms of angioedema, necessitating specific laboratory testing for confirmation. Key clinical indicators that should raise suspicion for HAE include:

• Recurrent episodes of angioedema without urticaria (hives), typically lasting 2-5 days.
• A lack of response to high-dose antihistamines and corticosteroids.
• The absence of common angioedema triggers such as ACE inhibitors, NSAIDs, or allergies.

When clinical suspicion for hereditary angioedema (HAE) arises, evaluation typically begins with the most critical diagnostic indicators: SERPING1 gene analysis, C1 esterase inhibitor (C1INH) protein level, and C1INH functional activity. These markers are central to identifying the majority of HAE cases, particularly types I and II. However, these tests are susceptible to pre-analytical and analytical variability and require careful specimen handling and expert interpretation.

Additional markers such as C4—often reduced in affected individuals—and broader genetic testing for mutations in F12, PLG, and other genes including ANGPT1, KNG1, MYOF, and HS3ST6 can help identify rare forms of HAE with normal C1INH, collectively referred to as nC1-INH-HAE. Broad reference ranges and potential interference from medications can further obscure the diagnostic picture, highlighting the need for a comprehensive and nuanced approach.

The Power of Quest Data and Prognos Algorithms in Patient Identification

Quest Diagnostics, a national leader in laboratory testing, healthcare data, and analytics processed more than 1.1 million tests across approximately 840,000 patients were identified for C4 esterase, C1 inhibitor protein level, C1 inhibitor function, and C1q esterase from January 2025 through March 2026. This generates an unparalleled wealth of real-world data.

Prognos Health leverages its cutting-edge, proprietary algorithms to analyze de-identified data from Quest. By identifying specific patterns and combinations of key laboratory markers—particularly abnormal C1INH protein levels or functional activity, often accompanied by persistently low C4—Prognos can effectively identify individuals with a high likelihood of having hereditary angioedema (HAE). Importantly, this identification can occur even before a formal clinical diagnosis has been made.

By incorporating Quest data into its algorithms, Prognos is able to identify HCPs that may have potential HAE patients. This proactive identification capability empowers pharmaceutical companies with a significant opportunity to engage with the right physicians.

Empowering Pharma with Actionable Insights

The collaboration between Quest's comprehensive de-identified lab data and Prognos's sophisticated analytics delivers significant advantages for pharmaceutical commercial teams:

• Enhanced Patient Identification: Prognos's algorithms meticulously analyze Quest's de-identified lab data to identify individuals exhibiting lab profiles strongly suggestive of HAE, including those yet to receive a formal diagnosis. This enables targeted outreach and educational initiatives to HCPs who may be unaware that their patients may have HAE.
• Understanding the Burden of Disease: By analyzing the prevalence of specific lab markers associated with HAE within the Quest de-identified data, Prognos provides valuable insights into the true burden of this underdiagnosed condition within specific geographies and patient populations.
• Navigating the Evolving Treatment Landscape: Access to longitudinal lab data can help commercial teams understand how diagnostic patterns and treatment initiation are changing over time, allowing for more informed strategies in a dynamic therapeutic environment.
• Data-Driven Engagement: Prognos's insights into patient journeys, from initial lab tests to potential diagnosis, can inform marketing strategies, sales force deployment, and the development of educational materials for both patients and healthcare providers.
• Streamlined Operations: By identifying potential HAE patients earlier in their diagnostic journey, commercial teams can focus their resources more efficiently, accelerating the connection between HCPs and the therapies needed for their patients.

Furthermore, the Prognos Marketplace offers the unique ability to add additional relevant datasets, including other national and regional reference labs, academic and community labs, and specialty genomics labs, enriching the understanding of the patient journey and providing a more holistic view of individuals with HAE.

Collaborating to Expedite the HAE Patient Journey

Prognos Health and Quest Diagnostics are committed to empowering commercial teams in their mission to improve the lives of individuals affected by HAE. By providing access to lab data insights and sophisticated analytical tools, we aim to:

• Significantly reduce the time to diagnosis for HAE patients.
• Increase awareness of HAE and the benefits of timely treatment.
• Facilitate quicker access to life-changing therapies for those who need them.
• Ultimately alleviate the burden of this challenging condition.

"The collaboration between Quest Diagnostics' extensive HAE-related deidentified laboratory data and Prognos Health's advanced analytical capabilities," explains Parag More, Executive Director, Healthcare Analytics Solutions at Quest Diagnostics, "represents a significant step forward in addressing the underdiagnosis of this rare condition. By working together, we can find individuals with a high likelihood of HAE before a formal diagnosis, which may be crucial for enabling earlier therapeutic intervention and mitigating the burden of this debilitating condition."

If you are interested in learning more about how our data-driven solutions can help your commercial team effectively identify and support HAE patients, we invite you to talk with us further.