Sparsentan is a first-in-class oral dual endothelin-angiotensin receptor antagonist. It’s shown clear promise in treating focal segmental glomerulosclerosis (FSGS), where it works to substantively reduce proteinuria. In recent clinical trials, Sparsentan demonstrated a marked benefit compared to the standard of care, irbesartan. This groundbreaking decision demonstrates Sparsentan’s promise to become an effective weapon in treating this devastating kidney disease.
The phase 2 DUET trial had shown impressive results for Sparsentan. It had a higher rate of partial remission of proteinuria, 64.7% vs 43.9% with irbesartan. Furthermore, the proportional hazard of attaining the endpoint of partial remission with Sparsentan was found to be 1.48 when compared to irbesartan. These results demonstrate that Sparsentan effectively lowers proteinuria. It improves the likelihood for positive outcomes in patients suffering from FSGS.
Only after eight weeks of treatment, patients treated with Sparsentan experienced a significant greater reduction in proteinuria. By contrast, patients who had been on irbesartan saw significantly less improvement. That’s why an early and aggressive response is so important. Reducing proteinuria has been shown to provide a dramatic increase of kidney survival rates in those with FSGS.
“Sparsentan led to partial or complete remission of proteinuria earlier and more often in patients with FSGS than did angiotensin receptor blockade alone with irbesartan,” stated James Tumlin, MD, emphasizing the drug’s enhanced efficacy.
During the trial, they saw a robust 18.5% rate of complete remission of proteinuria when patients were on Sparsentan. In comparison, only 7.5% went into remission with irbesartan. The relative risk of achieving complete remission was 2.47 for Sparsentan compared to its counterpart. Collectively, these results suggest Sparsentan may offer a more differentiated therapeutic alternative for patients who are challenged by FSGS.
The primary endpoint of the DUET trial, change from baseline in eGFR slope at 108 weeks, was not statistically different between Sparsentan and irbesartan. The pre-specified secondary analysis showed Sparsentan as having substantial benefits by reducing proteinuria. “The current results of the DUPLEX trial data reinforce the antiproteinuric benefits of the dual endothelin receptor blockade and the importance of reaching either complete or partial remission,” noted Sankar D Navaneethan, MD.
Safety profiles for Sparsentan were determined to be similar as compared to those of irbesartan. The most frequent treatment-emergent adverse events were COVID-19, hyperkalemia, peripheral edema, and hypotension. “Safety data – especially fluid retention, presented up to 108 weeks is reassuring,” added Dr. Navaneethan.
Sparsentan received orphan drug designation from the US Food and Drug Administration (FDA) for the treatment of FSGS. It has gained such designation from the European Medicines Agency (EMA), its EU-counterpart. Today, it is approved for treating immunoglobulin A nephropathy (IgAN). “Sparsentan is approved for IgAN management. We will await further studies and regulatory approval for considering the use of sparsentan for management of FSGS,” Dr. Navaneethan stated.
Dr. Tumlin underscored the urgency surrounding effective treatments for FSGS: “There remains an unmet need for safe and effective treatments that lower proteinuria and reduce the risk of kidney failure.” Sparsentan’s unique potential to accomplish significant, meaningful reductions in proteinuria could go a long way towards relieving this urgent concern.
Importantly, the study found that patients who attained partial or complete remission were able to meaningfully decrease their risk of advancing to kidney failure. Conversely, participants who did not achieve remission were at significantly greater risk. Supporting nephroprotective benefit of Sparsentan in FSGS patients This finding further reinforces the nephroprotective benefit of Sparsentan seen in FSGS patients.
In fact, after 108 weeks, the Sparsentan group achieved 2.5 times the number of patients attaining complete remission than the irbesartan group, reported the authors. This finding is extremely important as it strongly supports the potential impact of Sparsentan on improving patient outcomes.
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