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First FSGS Drug Hits FDA Delay After 8-Year Clinical Journey

First FSGS Drug Hits FDA Delay After 8-Year Clinical Journey

Sparsentan approval extended to April as FDA requests more data on clinical benefit

Overview

No FDA-approved treatment for focal segmental glomerulosclerosis has ever existed. For the 40,000 Americans with this rare kidney disease—which drives half of patients to kidney failure within a decade—the only options have been off-label immunosuppressants with mixed results. On January 13, 2026, that was supposed to change. Instead, the FDA extended its review of sparsentan by three months, requesting more data on clinical benefit.

The delay centers on a fundamental question in kidney drug development: whether reducing protein in urine (proteinuria) actually prevents kidney failure. Sparsentan cut proteinuria by 50% in trials but failed to slow the rate of kidney function decline—the traditional gold standard. If the FDA approves sparsentan for FSGS based on proteinuria data alone, it would validate a faster pathway for future kidney drugs. If rejected, it could set back rare kidney disease drug development by years.

Key Indicators

40,000+
U.S. patients with FSGS
No FDA-approved treatment currently exists for this population.
0
FDA-approved FSGS drugs
FSGS remains without any specifically indicated treatment.
50%
Proteinuria reduction
Sparsentan achieved 50% reduction vs. 32% for comparator irbesartan at 108 weeks.
67-77%
Lower kidney failure risk
Patients achieving remission showed substantially reduced risk of end-stage kidney disease.
-33%
Stock drop on news
Travere shares fell as much as 33% intraday following the FDA extension announcement.

People Involved

EP
Eric Dube, Ph.D.
President and CEO, Travere Therapeutics (Leading company through FDA review process)

Organizations Involved

Travere Therapeutics
Travere Therapeutics
Biopharmaceutical Company
Status: Awaiting FDA decision on sparsentan for FSGS

Rare disease-focused biopharma company that developed sparsentan, the first non-immunosuppressive treatment for IgA nephropathy.

U.S. Food and Drug Administration
U.S. Food and Drug Administration
Federal Regulatory Agency
Status: Reviewing sparsentan sNDA with new April 13, 2026 PDUFA date

Federal agency responsible for approving drugs and determining whether surrogate endpoints like proteinuria predict clinical benefit.

Timeline

  1. FDA Extends Review by Three Months

    Regulatory

    FDA classifies Travere's responses to data requests as a Major Amendment, extending PDUFA date to April 13, 2026. No safety or manufacturing concerns cited.

  2. FDA Cancels Advisory Committee

    Regulatory

    FDA determines advisory committee review is no longer necessary for sparsentan FSGS application.

  3. FDA Accepts FSGS Application

    Regulatory

    FDA accepts sparsentan sNDA for traditional approval in FSGS with original PDUFA date of January 13, 2026.

  4. FDA Holds FSGS Endpoint Workshop

    Regulatory

    FDA convenes scientific workshop to discuss proteinuria and GFR as clinical trial endpoints specifically for FSGS drug development.

  5. Full IgA Nephropathy Approval Granted

    Regulatory

    FDA converts sparsentan's accelerated approval to traditional approval based on confirmatory two-year kidney function data from PROTECT trial.

  6. DUPLEX Primary Endpoint Misses

    Clinical Trial

    Two-year results show sparsentan failed to significantly slow eGFR decline (the primary endpoint) compared to irbesartan, despite achieving greater proteinuria reduction.

  7. FDA Grants Accelerated Approval for IgA Nephropathy

    Regulatory

    Sparsentan receives accelerated approval for reducing proteinuria in IgA nephropathy, becoming the first non-immunosuppressive treatment for this related kidney disease.

  8. 36-Week Interim Results Show Proteinuria Benefit

    Clinical Trial

    DUPLEX interim analysis demonstrates sparsentan achieves statistically significant proteinuria reduction at 36 weeks compared to irbesartan.

  9. DUPLEX Enrollment Complete

    Clinical Trial

    Travere announces completion of patient enrollment with 371 patients randomized across study sites worldwide.

  10. DUPLEX Trial Enrollment Begins

    Clinical Trial

    Travere initiates enrollment in the Phase 3 DUPLEX study, comparing sparsentan to irbesartan in patients with biopsy-proven FSGS. The trial would become the largest interventional study in FSGS history.

Scenarios

1

FDA Approves Sparsentan as First FSGS Treatment

Discussed by: Stifel analysts, nephrology researchers, Kidney Health Initiative

FDA grants traditional approval based on proteinuria reduction and remission data, accepting that patients achieving remission showed 67-77% lower kidney failure risk. This would validate proteinuria as a regulatory endpoint for FSGS and open the pathway for competing drugs in development.

2

Complete Response Letter Requires Additional Trials

Discussed by: Stifel analysts, BioPharma Dive

FDA issues a Complete Response Letter citing insufficient evidence that proteinuria reduction translates to kidney function preservation in FSGS. The primary endpoint miss on eGFR slope becomes the deciding factor. Travere would need to conduct additional studies, potentially delaying approval by years.

3

Accelerated Approval with Confirmatory Trial Requirement

Discussed by: FDA regulatory analysts, rare disease advocacy groups

FDA grants accelerated approval based on proteinuria as a surrogate endpoint, contingent on confirmatory trials demonstrating kidney function benefit. This mirrors the pathway used for IgA nephropathy drugs and would get treatment to patients faster while requiring continued evidence generation.

4

Narrow Approval for Specific FSGS Subpopulation

Discussed by: Clinical nephrologists, trial investigators

FDA approves sparsentan for a subset of FSGS patients—potentially those with genetic mutations in podocyte proteins or those achieving complete remission—where clinical benefit evidence is strongest. This would limit commercial potential but establish a treatment foothold.

Historical Context

Tarpeyo IgA Nephropathy Approval (2021-2023)

December 2021 - December 2023

What Happened

Calliditas Therapeutics' Tarpeyo (budesonide) became the first drug approved for IgA nephropathy in December 2021 under accelerated approval, based solely on proteinuria reduction. The FDA required confirmatory data showing kidney function benefit.

Outcome

Short Term

Patients gained access to first indicated treatment while long-term data collection continued.

Long Term

Two-year data showed 50% less kidney function decline versus placebo. FDA granted full approval December 2023, validating the surrogate endpoint approach.

Why It's Relevant Today

Demonstrates FDA willingness to accept proteinuria as a pathway to accelerated approval in rare kidney disease, though FSGS differs in that sparsentan is seeking traditional (not accelerated) approval.

Eteplirsen Duchenne Approval Controversy (2016)

September 2016

What Happened

FDA granted accelerated approval to eteplirsen for Duchenne muscular dystrophy based on a tiny increase in dystrophin protein (0.28% of normal levels) in just 12 patients. An advisory committee voted against approval. Two FDA reviewers resigned in protest.

Outcome

Short Term

CDER director Janet Woodcock overruled FDA scientific staff to grant approval. Patients gained access to treatment priced at $300,000 annually.

Long Term

As of 2025, confirmatory trials remain incomplete. FDA approved three more DMD drugs using the same surrogate endpoint. The case became emblematic of tension between patient access and evidence standards.

Why It's Relevant Today

Illustrates the stakes when surrogate endpoints lack clear connection to clinical outcomes. Sparsentan's situation differs: proteinuria-to-kidney-failure link is better established, but the primary eGFR endpoint failure raises similar questions about evidence thresholds.

FDA Accelerated Approval Reforms (2022)

December 2022

What Happened

Congress passed reforms requiring drug companies to complete confirmatory trials more quickly and giving FDA clearer authority to withdraw accelerated approvals when trials fail or aren't completed. The FDA also began withdrawing approvals for cancer drugs that failed to confirm benefit.

Outcome

Short Term

Multiple accelerated approvals were voluntarily withdrawn by manufacturers when confirmatory trials failed.

Long Term

FDA established stricter standards for surrogate endpoints and confirmatory trial timelines, raising the bar for new accelerated approvals.

Why It's Relevant Today

Creates context for FDA's careful approach to sparsentan FSGS approval. The agency faces pressure to ensure surrogate endpoints truly predict clinical benefit before granting approval, even as patients await treatment.

9 Sources:
+3
Business Wire New England Journal of Medicine Travere Therapeutics Investor Relations HCPLive U.S. Food and Drug Administration Kidney International Reports (PMC) Travere Therapeutics The Cardiology Advisor BioPharma Dive