Retrophin Announces Enrollment of First 190 Patients in Pivotal Phase 3 Study

Retrophin, Inc. recently announced that the first 190 patients have been enrolled in the pivotal Phase 3 DUPLEX Study evaluating the safety and efficacy of sparsentan in focal segmental glomerulosclerosis (FSGS). The DUPLEX Study protocol provides for a pre-specified interim analysis to evaluate the proteinuria efficacy endpoint in the first 190 patients after 36 weeks of treatment. Successful achievement of this 36-week proteinuria endpoint is expected to serve as the basis for submission of filings for accelerated approval in the US and Europe. Topline efficacy data from the 36-week proteinuria endpoint analysis are expected in the first quarter of 2021.

“Many people living with FSGS face a progression to kidney failure with no FDA or EMA approved medicine indicated for their condition,” said Noah Rosenberg, MD, Chief Medical Officer of Retrophin. “Our continued collaboration with investigators and the FSGS community has generated recent momentum in the DUPLEX Study. Achieving 190 patients enrolled allows us to update the timing for topline data from the 36-week proteinuria analysis to the first quarter of next year, and brings us one step closer to realizing our goal for sparsentan to potentially shape the treatment paradigm for FSGS, if approved.”

DUPLEX is a global, randomized, multicenter, double-blind, parallel-arm, active-controlled Phase 3 clinical trial expected to enroll approximately 300 patients with FSGS. Patients are randomized to receive either sparsentan or irbesartan, the active control. The proteinuria efficacy endpoint is the proportion of patients achieving FSGS partial remission of proteinuria (FPRE), which is defined as urine protein-to-creatinine ratio (Up/C) ≤1.5 g/g and a >40 percent reduction in Up/C from baseline, at Week 36. The confirmatory endpoint of the study is the slope of estimated glomerular filtration rate (eGFR) from Week 6 to Week 108, in approximately 300 patients.

FSGS is a rare kidney disorder that is estimated to affect up to 40,000 patients in the US with similar prevalence in Europe. The disorder is defined by progressive scarring of the kidney and often leads to end-stage renal disease (ESRD). FSGS is characterized by proteinuria, where protein is found in the urine due to a breakdown of the normal filtration mechanism in the kidney. Other common symptoms include swelling in parts of the body, known as edema, as well as low blood albumin levels, abnormal lipid profiles and hypertension.

Reduction in proteinuria appears to be beneficial in the treatment of FSGS and may be associated with a decreased risk of progression to ESRD. Achieving FPRE appears to be associated with long-term preservation of renal function in patients with FSGS. Symptoms of FSGS are currently managed with angiotensin receptor blockers, angiotensin converting enzyme inhibitors, steroids, or calcineurin inhibitors.

Sparsentan is an investigational product candidate in Phase 3 clinical development that has a dual mechanism of action combining endothelin receptor type A blockade with angiotensin receptor blockade. Retrophin is developing sparsentan for the treatment of FSGS, as well as for IgA nephropathy (IgAN), rare kidney disorders that often lead to ESRD. In several forms of chronic kidney disease, such as FSGS and IgAN, endothelin receptor blockade has been shown to have an additive beneficial effect on proteinuria in combination with renin-angiotensin blockade via angiotensin receptor blockade or angiotensin converting enzyme inhibitors. Sparsentan has been granted orphan drug designation for the treatment of FSGS by the FDA and European Commission.

Retrophin is currently enrolling the pivotal Phase 3 DUPLEX Study of sparsentan for the treatment of FSGS (FSGSduplex.com), as well as the pivotal Phase 3 PROTECT Study of sparsentan for the treatment of IgAN (IgANprotect.com). Both studies contain 36-week proteinuria-based endpoints, which if achieved, are expected to serve as the basis for submission of a New Drug Application (NDA) under the Subpart H accelerated approval pathway in the US as well as an application for Conditional Marketing Authorization (CMA) consideration in Europe. If approved, sparsentan could potentially be the first medicine approved for FSGS and IgAN.

Retrophin is a biopharmaceutical company specializing in identifying, developing, and delivering life-changing therapies to people living with rare disease. The company’s approach centers on its pipeline featuring sparsentan, a product candidate in late-stage development for focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN), rare disorders characterized by progressive scarring of the kidney often leading to end-stage renal disease. Research in additional rare diseases is also underway, including partnerships with leaders in patient advocacy and government research to identify potential therapeutics for NGLY1 deficiency and Alagille syndrome, conditions with no approved treatment options. Retrophin’s R&D efforts are supported by revenues from the company’s commercial products Chenodal, Cholbam, Thiola, and Thiola EC. For more information, visit Retrophin.com.