Why Sparsentan’s FDA Approval Marks a Turning Point in FSGS, With Howard Tratchman, MD

Sparsentan (Filspari)’s approval by the US Food and Drug Administration (FDA) marks a major milestone as the first therapeutic option to treat focal segmental glomerulosclerosis (FSGS).1

The April 13, 2026 decision was supported by data from the phase 2 DUET and phase 3 DUPLEX trials, 2 of the largest head-to-head interventional studies in adult and pediatric patients with FSGS.1,2

Sparsentan is a first-in-class dual endothelin and angiotensin II receptor antagonist that simultaneously targets endothelin type A (ETA) and angiotensin II type 1 (AT1) receptors. By inhibiting AT1, it reduces angiotensin II–mediated vasoconstriction and intraglomerular pressure. Simultaneously, by blocking the ETA receptor, sparsentan reduces inflammation, vasoconstriction, and fibrosis, and may help limit podocyte injury.1

Through dual pathway inhibition, sparsentan has been shown to reduce proteinuria beyond what is achievable with maximal renin–angiotensin system blockade alone, with clinical data suggesting potential long-term kidney protective effects, including slowing the progression of kidney function decline.1

Howard Trachtman, MD, an adjunct clinical professor of pediatrics at the University of Michigan, who served as a study investigator of the phase 3 DUPLEX trial, spoke about the implications and importance of this latest approval in an interview with HCPLive.

HCPLive: Sparsentan was approved yesterday as the first FDA-approved therapy for FSGS—what does this approval mean for the field and for patient care?

Trachtman: It’s really, it’s an important milestone. It’s the first drug. Historically, FSGS has been like a graveyard for drug development. It’s a difficult disease, its outcomes are bad, and there’s been really marginal understanding of the pathophysiology of the disease.

So it’s been—I mean, I’ve been at this for a very long time—and most sponsors are very, very reluctant to get into the space. Diabetic kidney disease just really dwarfed any activity with regard to the primary glomerular diseases.

So the fact that people are finally paying attention to the disease—it’s even though it’s uncommon, I hate the word rare, but it’s uncommon—the health burden is enormous.

So there were just no treatments, no documented therapies that people would rely upon, that they did at accurate dosing, they did the side effect profile, and they could confidently talk to patients and to their parents and caregivers and say, “Well, this is what I would expect to happen with this drug.”

It’s just really a fantastic accomplishment. The drug itself is interesting because it combines antagonism of two pathways. But in the work that I’m involved with, and people at Michigan, there may be people who have more pronounced activation of the endothelin pathway who may be really poised to respond even better than average.

But this is a renal protective therapy. It works in patients with FSGS to achieve an important biological effect, namely reduction in proteinuria.

And again, the last thing I think that’s so important is that the approval was based on an endpoint that really opens the door to engagement with pharmaceutical companies, so that they know they have a measure of efficacy that can be considered by regulators.

As we really accelerate the scientific understanding of the heterogeneity of FSGS, clearly more drugs are going to come to the clinic for testing. And this trial really sets a standard that it can be done.

HCPLive: You mentioned the trial opens the door for FSGS and more drugs being developed—can you tell us a little bit more about the data that leads you to believe in this positive future for the field?

Trachtman: With regard to the drug per se, again, what it is is a combination of the portion of the molecule that inhibits the renin–angiotensin system via angiotensin II type 1 receptor blockade, coupled with blockade of endothelin. Endothelin in and of itself is key. It’s documented to be a part of the pathophysiology of the disease.

And the fact that we know that these two injury pathways interact with one another, blocked simultaneously with a drug that, based on the coupled experience of DUET and DUPLEX, has a reassuring safety profile, is really, really valuable.

What the data show is that it causes an incremental reduction in proteinuria over and above what can be achieved with renin–angiotensin system blockade.

Knowing what we know about the data about the role of SGLT2 inhibitors in the context of FSGS—it’s a little bit inconclusive—it adds to what should I say, the elements of that renal protective box that can be offered to patients to lower proteinuria.

I think we’re learning that the better you do as clinicians lowering proteinuria, the better outcomes are for patients.

So I think what we’re seeing overall, depending on the different way that the FDA analyzed the data, is about a 20 to 25% incremental reduction in proteinuria over current standard of care.

HCPLive: As you’ve mentioned proteinuria reduction, can you talk a little bit more about the other clinical markers investigators have seen with sparsentan, particularly in the context of eGFR slope and long-term kidney outcomes?

Trachtman: It’s a great question. In the context of DUPLEX, and the open-label extension from DUET, the data would suggest that achieving these reductions in proteinuria at 2 years are clinically meaningful long term.

What PARASOL taught us was that it was implausible to document clinically meaningful changes in renal function preservation in a 2-year trial.

So with the DUPLEX data, all of it—whether it was the number of patients that had 40% decline in eGFR, 30% decline in eGFR, or who started to reach the endpoint of kidney failure—all of these endpoints trended towards a benefit of sparsentan.

None of them are statistically significant because the numbers are too small, the follow-up is too short, and the disease variability is high.

And in this study, there was a modest slowing in eGFR decline over the 2-year period.

But I think that, hopefully, as a community, we can organize and make sure that data is collected post-marketing. The nephrology community—we can get better at this. PARASOL shows that we actually can work together collegially and productively.

We can continue to monitor the long-term efficacy of sparsentan, showing that the proteinuria reduction and the clinical benefit will manifest 3, 4 years down the road in terms of preservation of kidney function and delaying the time that patients need to start dialysis or receive a kidney transplant.

HCPLive: Looking ahead, as you know, there are still plenty of unmet needs in FSGS management—what are the greatest unmet needs that remain, and what should be the next priorities to improve clinical care?

Trachtman: Again, a very good question. I think the most important thing is to enhance our understanding of the underlying mechanisms of glomerular and podocyte injury that lead to FSGS.

We know that it’s not a single disease entity, and it’s a reflection of injury to the podocyte based on genetic factors, immunological factors, metabolic factors, and different signaling pathways.

I think the thrust of the research effort should be to improve our understanding of these different pathways. Couple that with thoughtful, rational development of drugs that can target these pathways.

And then making sure that we target the right drug to the right patient with FSGS, knowing that they’re not all the same—they’re subtypes—and we need to refine our understanding, our ability to resolve those subtypes, and then therefore pair the patient with a subtype with the appropriate medication.

HCPLive: What do you hope to come out of this approval for the nephrology community?

Trachtman: I think the only other key thing is that this approval of sparsentan really represents an important accomplishment in the nephrology community, where you really did have alignment of all the critical forces.

Patients were advocating for this, doctors were doing the work, other clinical researchers were designing clinical trials that leveraged basic science.

And I think this needs to be really like a model, a paradigm for how the community has to work together—listen to the patient voice, define priorities in terms of treatments, and then husband industry resources and couple them with academic centers so progress can be made.

These are hard diseases to study, and cooperation and collaboration is going to be key to really move the ball forward consistently.

References

1. Hillenbrand A. FDA Approves Sparsentan for Focal Segmental Glomerulosclerosis. HCPLive. Published April 11, 2026. Accessed April 14, 2026. https://www.hcplive.com/view/fda-approves-sparsentan-for-focal-segmental-glomerulosclerosis

2. Johnson V. DUPLEX: Sparsentan Outperforms Irbesartan in Reaching Key Proteinuria Threshold in FSGS. HCPLive. Published 2025. Accessed April 14, 2026. https://www.hcplive.com/view/duplex-sparsentan-outperforms-irbesartan-key-proteinuria-threshold-fsgs