Breakthrough Clinical Results
Travere Therapeutics announced it will present new data on FILSPARI (sparsentan) at the International Podocyte Conference. Data from the Phase 2 SPARTAN study shows FILSPARI's antifibrotic and anti-inflammatory effects in IgA nephropathy (IgAN), impacting B cell and complement pathways. The presented data includes biomarker analysis revealing rapid intrarenal anti-inflammatory and antifibrotic effects. Additional data will be presented on FILSPARI's effects in patients with Focal Segmental Glomerulosclerosis (FSGS) and its direct effects on the glomerular capillary wall. FILSPARI is currently approved to slow kidney function decline in adults with IgAN at risk for disease progression.
Key Highlights
- New biomarker data from the Phase 2 SPARTAN Study shows FILSPARI's rapid and sustained reductions in urinary BAFF and sC5b9, suggesting disease-modifying activity in IgA nephropathy.
- Data demonstrates FILSPARI's antifibrotic and anti-inflammatory action in IgA nephropathy.
- Presentations will cover FILSPARI's effects in patients with Focal Segmental Glomerulosclerosis (FSGS).
- FILSPARI's direct effects on the glomerular capillary wall to attenuate increased permeability in nephrotic syndrome models will be discussed.
Incidence and Prevalence
IgA Nephropathy (IgAN) Incidence and Prevalence:
Determining precise global incidence and prevalence of IgAN is challenging due to variations in diagnostic practices, access to healthcare, and research methodologies across different regions. While a single, definitive global estimate is not available in the provided PubMed articles, several studies offer valuable insights into IgAN epidemiology:
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United States: A 2021 U.S. study estimated an annual incidence of 2.1-2.2 per 100,000 and a prevalence of 59.9-62.7 per 100,000. Another U.S. study within a large health system reported a slightly lower standardized incidence of 1.4 per 100,000 person-years between 2010 and 2021. These studies highlight the variability even within a single country, depending on data source and methodology.
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Regional Variations: A systematic review of studies prior to 2015 indicated higher IgAN frequency in Asian populations (e.g., 45 cases per million population/year in Japan) compared to Caucasians (e.g., 31 cases per million population/year in France). This review emphasized the impact of systematic urine screening practices, which are more common in some Asian countries, leading to earlier detection and potentially higher reported incidence.
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Socioeconomic Factors: A study in West and Central Scotland found a higher likelihood of IgAN diagnosis in areas of socioeconomic deprivation, suggesting potential influences of environmental or lifestyle factors on disease development or access to diagnostic services.
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Challenges in Global Estimation: The available literature underscores the difficulties in establishing a truly global IgAN incidence and prevalence. Factors such as variations in biopsy practices, access to specialized renal care, and the underdiagnosis of asymptomatic or mild cases contribute to this challenge. Furthermore, differences in study methodologies, case definitions, and data sources (e.g., biopsy registries, insurance claims, electronic health records) can lead to discrepancies in reported estimates.
Future Directions:
To improve global IgAN epidemiology, future research should prioritize:
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Standardized diagnostic criteria and reporting: Consistent application of diagnostic criteria (e.g., Oxford classification) and standardized reporting of incidence and prevalence data are crucial for comparability across studies and regions.
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Increased research in understudied regions: More epidemiological studies are needed in low- and middle-income countries, as well as regions with limited data, to better understand the true global burden of IgAN.
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Exploration of risk factors: Investigating potential environmental, genetic, and lifestyle risk factors can provide insights into disease etiology and inform preventive strategies.
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Improved data collection and surveillance: Establishing robust surveillance systems and utilizing large, diverse datasets can enhance the accuracy and representativeness of IgAN epidemiological estimates.
By addressing these challenges, future research can provide a more complete and accurate picture of the global burden of IgAN, ultimately leading to improved patient care and targeted interventions.
Economic Burden
IgA Nephropathy (IgAN) Economic Burden:
USA:
A 2019 study estimated the total economic burden of rare diseases (RDs), including IgAN, in the US to be $997 billion. This included $449 billion in direct medical costs, $437 billion in indirect costs, $73 billion in non-medical costs, and $38 billion in uncovered healthcare costs. This study used a prevalence-based approach, combining prevalence data for 379 RDs with per-person direct and indirect costs. Claims data from Medicare, Medicaid, and Optum were used for prevalence and direct medical costs, while a primary survey provided estimates for indirect and non-medical costs.
Europe:
A 2023 study analyzed the clinical and economic burden of low back pain (LBP) in high-income countries (HICs), including several European nations. While this study did not focus specifically on IgAN, it provides insights into the broader economic burden of diseases in Europe. The study found that the average annual direct and indirect costs per population for LBP ranged from €2.3 billion to €2.6 billion and €0.24 billion to $8.15 billion, respectively. This study used a systematic review and meta-analysis of studies from America, Europe, and the Western Pacific. Direct and total costs of LBP per patient were also estimated.
A 2017 study estimated the economic burden of Huntington's disease (HD) in five European countries and the USA. While not specific to IgAN, it offers insights into the economic burden of a rare disease in Europe. The study found that the annual direct medical costs for HD were €12,663, non-direct medical costs were €2,984, and indirect costs were €47,576. Costs were higher in later stages of the disease. This study used a retrospective, cross-sectional design, collecting data via physician-completed case report forms and optional patient and caregiver questionnaires.
A 2021 study estimated the incidence and prevalence of IgAN in Europe using data from national registries. The estimated annual IgAN incidence was 0.76 per 100,000 people across 10 European countries. The corresponding pooled IgAN point prevalence was 2.53 per 10,000, ranging from 1.14 per 10,000 in Spain to 5.98 per 10,000 in Lithuania. Based on these figures, the number of expected prevalent IgAN cases in 2021 was estimated to be 47,027 across the 10 countries. This study focused on epidemiological data rather than economic burden.
Summary:
While precise, recent estimates of the economic burden of IgAN specifically within Europe are limited in the provided context, data on the broader economic burden of rare diseases and other conditions in Europe offer some perspective. The US data suggests a substantial economic burden associated with rare diseases, including IgAN. Further research focusing specifically on the economic impact of IgAN in Europe is needed to provide more accurate and detailed estimates.
Drug used in other indications
Sparsentan (FILSPARI) is also being developed for the treatment of focal segmental glomerulosclerosis (FSGS).
One study, DUET, was a phase 2, randomized, double-blind, active-control study. It compared sparsentan (200, 400, or 800 mg/d) to irbesartan (300 mg/d) for 8 weeks in patients with FSGS. After 8 weeks, patients transitioned to open-label sparsentan. The primary endpoint was the reduction in urinary protein-to-creatinine ratio (UP/C) at 8 weeks. Secondary endpoints included the proportion of patients achieving FSGS partial remission (UP/C ≤1.5 g/g and >40% reduction from baseline) and changes in blood pressure and estimated glomerular filtration rate (eGFR).
Another study, DUPLEX, is a phase 3, multicenter, international, randomized, double-blind, active-controlled study comparing sparsentan to irbesartan in patients with FSGS. Approximately 300 patients will be randomized to receive daily treatment for 108 weeks. The primary endpoint is the slope of eGFR from week 6 to week 108. A key secondary endpoint is the proportion of patients achieving FPRE at a planned interim analysis at week 36.