Summary

The sparsentan Phase 3 DUPLEX trial is the largest interventional focal segmental glomerulosclerosis (FSGS) trial to date¹*

Background

Focal segmental glomerulosclerosis (FSGS) is defined as a histological lesion characterized by segmental accumulation of the glomerular extracellular matrix.² This results in capillary obliteration and glomerular scarring.²

Patients with FSGS often present with nephrotic syndrome and a varying degree of proteinuria.² Patients with FSGS are typically treated with renin angiotensin-aldosterone system (RAAS) inhibitors in combination with immunosuppressive regimens.^3,4 But there is still an unmet need for more tolerable and effective treatments.⁵

Sparsentan is a non-immunosuppressive, single-molecule dual endothelin and angiotensin receptor antagonist.^6,7

Aim

The objective of the Phase 3 DUPLEX study is to evaluate the long-term efficacy and safety of sparsentan compared with the active comparator irbesartan in FSGS.¹ This manuscript aims to describe the baseline characteristics of the enrolled patients.¹

Approach

DUPLEX is a large, international, randomized, double-blind, interventional Phase 3 study of sparsentan in FSGS.¹ Patients were randomized to receive sparsentan 800 mg or irbesartan 300 mg.¹ Key eligibility criteria included¹:

Those with a known secondary cause of FSGS or serological test findings diagnostic of another primary or secondary glomerular disease were excluded.¹

Baseline characteristics were analyzed, including by race and geographic region.¹ Evaluating by race and geography may help characterize differences in FSGS presentation.¹ Analysis also included genotype testing and mapping of pathogenic variants in podocyte proteins associated with FSGS.¹

Findings

Demographic and clinical baseline characteristics

The enrolled population (N=371) primarily consisted of White adults (73%, 271/371) from North America (38.8%, 144/371) and Europe (36.1%, 134/371) with a median age of 42 years (range: 27.0-56.0).¹

The median age at diagnosis was 37 years (interquartile range: 23.0-51.0).¹ Key baseline clinical and laboratory assessments included¹:

There was a wide distribution across eGFR ranges corresponding to chronic kidney disease (CKD) stages 1 to 3b.¹

Clinical and laboratory findings varied by race and geographic regions.¹

Genetic baseline characteristics

Of the 352 patients with evaluable samples, 9.4% (33/352) had pathogenic or likely pathogenic (P/LP) variants of genes essential to podocyte structural integrity and function.¹

P/LP variants of collagen genes were identified in 7.7% (27/352) of patients, and 4.0% (14/352) of patients had APOL1 high risk variants.¹

Key takeaway

Baseline characteristics were geographically broad and clinically diverse.¹ The sparsentan phase 3 DUPLEX trial will identify the treatment effect of sparsentan across a heterogeneous FSGS patient population.¹

Footnotes

As of July 2024, sparsentan is not FDA approved for the treatment of FSGS.

CKD, chronic kidney disease; DEARA, dual endothelin and angiotensin receptor antagonist; eGFR, estimated glomerular filtration rate; FDA, Food and Drug Administration; FSGS, focal segmental glomerulosclerosis; IgA, immunoglobulin A; P/LP, pathogenic or likely pathogenic; RAAS, renin angiotensin-aldosterone system; UPCR, urine protein-to-creatinine ratio.

*As of July 2024.

MA-SP-24-0055 | August 2024