Jonathan Barratt, PhD, FRCP: Sparsentan Full FDA Approval, Future IgAN Developments

Among the most active therapeutic pipelines of any rare disease in recent years is that of IgA nephropathy (IgAN), with the latest advancement being the full US Food and Drug Administration (FDA) approval of sparsentan (Filspari) for reducing the loss of kidney function.¹

In 2023, the nephrology community saw the first full FDA approval of a treatment for reducing the loss of kidney function in adults with primary IgAN with budesonide (Tarpeyo) delayed release capsules.² Less than a year later, sparsentan (Filspari) became the second IgAN therapeutic to demonstrate a significant impact on kidney function loss and subsequently earn full FDA approval.¹

“The treatments that we had available up until a year or so ago were essentially renin-angiotensin system inhibitors, general blood pressure control, and systemic glucocorticoids,” Jonathan Barratt, PhD, FRCP, Mayer Professor of Renal Medicine at the University of Leicester, said to HCPLive. “That's changed over the last couple of years. We now have the introduction of Nefecon and sparsentan, both of which have been shown to slow the rate of loss of kidney function in a much more effective way than what we've had for the last 30 years.”

He described this progress as “great news for patients” but was careful to note that “we’re not there yet” and more work is needed to prevent kidney failure in patients with IgAN. Currently, only budesonide and sparsentan have demonstrated an impact on reducing kidney function loss in clinical trials and are thus the only fully FDA-approved treatments for IgAN.

Reflecting on the recent full approval of sparsentan, Barratt emphasized the drug’s novel mechanism of action allowing for blockage of both the renin-angiotensin system and the endothelial system. Specifically, he pointed to phase 3 data from the PROTECT trial demonstrating the benefit of blocking both the renin-angiotensin system and the endothelial system with sparsentan as opposed to blocking the renin-angiotensin system alone with irbesartan.

Although not yet fully approved, 2024 has also seen the accelerated approval of iptacopan (Fabhalta) for proteinuria reduction in primary IgAN. With atrasentan in phase 3 development and a number of other agents in earlier stages of clinical development, the next few years show promise for more developments in IgAN.^3,4

“Having had no drugs approved for the past 50 years in IgA nephropathy, we now have 4 in the space of the last couple of years, which is fantastic,” Barratt said. “I would hope we're likely to have a couple more drugs approved each year for the next 2 or 3 years.”

Relevant disclosures of interest for Barratt included Argenx, Calliditas Therapeutics, Chinook Therapeutics, Galapagos NV, GSK, Novartis, and Travere Therapeutics.

References

1. ^{Brooks, A. FDA Approves Travere Therapeutics’ Sparsentan for Proteinuria Reduction in Adult Primary IgAN. HCPLive. September 5, 2024. Accessed September 6, 2024. https://www.hcplive.com/view/fda-approves-travere-therapuetics-sparsentan-for-proteinuria-reduction-in-adult-primary-igan}
2. ^{Brooks, A. FDA Awards Full Approval to Budesonide (Tarpeyo) in Treatment of IgA Nephropathy. HCPLive. December 20, 2023. Accessed September 6, 2024. https://www.hcplive.com/view/fda-awards-full-approval-to-budesonide-tarpeyo-in-treatment-of-iga-nephropathy}
3. ^{Campbell, P. Iptacopan Receives Accelerated Approval for Reducing Proteinuria in IgA Nephropathy. HCPLive. August 7, 2024. Accessed September 6, 2024. https://www.hcplive.com/view/iptacopan-receives-accelerated-approval-for-reducing-proteinuria-in-iga-nephropathy}
4. ^{Brooks, A. Atrasentan Achieves Positive Topline Results in Phase 3 Trial for IgA Nephropathy. HCPLive. October 30, 2023. Accessed September 6, 2024. https://www.hcplive.com/view/atrasentan-achieves-positive-topline-results-in-phase-3-trial-for-iga-nephropathy}