An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *
Bayer’s KERENDIA® (finerenone) Receives FDA Approval as the First New Treatment in 30 Years for Adults with Chronic Kidney Disease (CKD) and Type 1 Diabetes
KERENDIA® (finerenone), a non-steroidal mineralocorticoid receptor antagonist (MRA), is the first new treatment in more than 30 years approved by the FDA for adult patients with chronic kidney disease (CKD) associated with type 1 diabetes.
On Sept. 17, Bayer announced that the U.S. Food and Drug Administration (FDA) approved KERENDIA® (finerenone) to reduce urinary albumin-to-creatinine ratio (UACR), which is expected to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline and end-stage kidney disease in adults with chronic kidney disease (CKD) associated with type 1 diabetes (T1D), following the agency’s Priority Review of the supplemental New Drug Application (sNDA).
Key Facts
- The FDA approved KERENDIA to reduce UACR, which is expected to slow chronic kidney disease progression in adults with CKD associated with T1D. This approval is important for patients, as it is the first proven therapeutic advance in CKD associated with T1D in more than 30 years.
- Approval was supported by data from the Phase III FINE-ONE clinical trial in adult patients with CKD associated with T1D. It was also supported by Phase III data from the FIDELIO-DKD and FIGARO-DKD trials in adults with CKD associated with type 2 diabetes (T2D).
- Approximately 20-30% of people in the U.S. with T1D also have CKD, which puts them at risk of kidney disease progression and kidney failure.
- KERENDIA is also approved to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adult patients with CKD associated with T2D.
- In addition, KERENDIA is approved to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adult patients with heart failure with left ventricular ejection fraction (HF LVEF) ≥40%.
Why This FDA Approval Matters for Patients and Physicians
“For more than three decades, people with chronic kidney disease and type 1 diabetes have had limited options to address the risk of kidney disease progression,” said Dr. Janet McGill, Professor of Medicine in the Division of Endocrinology, Metabolism, and Lipid Research at Washington University School of Medicine in St. Louis, and Co-Chair of the study’s Executive Committee. “The approval of KERENDIA to reduce UACR, which is expected to slow chronic kidney disease progression in adults with type 1 diabetes, provides an important new treatment option for a population that has continued to face substantial unmet need.”
KERENDIA, a once-daily, oral treatment option, is the only MRA indicated for adults with CKD associated with either T2D or T1D.
“This approval builds on evidence linking reductions in UACR with improved kidney outcomes in KERENDIA’s clinical trial program in chronic kidney disease associated with type 2 diabetes,” said Carolina Aldworth, M.D., MSc, Executive Medical Director at Bayer. “KERENDIA’s third indication validates the breadth of its clinical trial program across cardiovascular and kidney diseases, helping a patient population that has historically been clinically underserved.”
FINE-ONE Clinical Trial Results
FINE-ONE (NCT05901831) was a pivotal, global, randomized, prospective, double-blind, placebo-controlled, multicenter, Phase III study in adult patients with CKD associated with T1D. FINE-ONE enrolled 242 adult participants with the primary objective to demonstrate whether the addition of KERENDIA, 10 mg or 20 mg once daily, to standard of care was superior to placebo in reducing UACR over six months (averaged over months 3 and 6). UACR is an important marker of CKD progression.
The results showed:
- KERENDIA significantly reduced UACR vs. placebo over 6 months (p=0.0001). Reductions in UACR were observed as early as Month 3 and were sustained through Month 6.
- At Month 3, KERENDIA reduced UACR compared to placebo by 22% (ratio of Least Square Geometric Mean Ratio [LSGMR] of 0.78; 95% CI: 0.68, 0.90).
- At Month 6, KERENDIA reduced UACR compared to placebo by 28% (ratio of LSGMR of 0.72; 95% CI: 0.60, 0.86).
- Safety and tolerability were consistent with the existing evidence for KERENDIA in adults with CKD associated with T2D.
- The rate of treatment-emergent adverse events was 47.1% for those treated with KERENDIA and 49.2% for placebo.
- The rate of treatment-emergent serious adverse events was 11.8% for KERENDIA and 11.5% for placebo.
- Hyperkalemia, an adverse event of special interest, was observed more frequently with KERENDIA (10.1%) compared to placebo (3.3%). The rate of treatment discontinuation due to hyperkalemia was 1.7% and 0%, respectively.
Detailed FINE-ONE trial results were presented at the American Society of Nephrology (ASN) Kidney Week 2025 and published in the New England Journal of Medicine.
Why Managing UACR Matters
UACR is a modifiable risk factor associated with chronic kidney disease progression.2In the FIDELIO-DKD and FIGARO-DKD trials, reductions in UACR with KERENDIA were shown to be associated with improved kidney outcomes in adults with CKD and T2D. Together with the FINE-ONE results, this evidence supported the use of UACR to bridge KERENDIA’s established kidney outcomes evidence from CKD associated with T2D to patients with CKD associated with T1D.
KERENDIA’s Approved Indications
Since 2021, KERENDIA has been approved by the FDA to reduce the risk of cardiovascular death, hospitalization for HF, non-fatal myocardial infarction, sustained eGFR decline and end-stage kidney disease in adult patients with CKD associated with T2D.
In July 2025, KERENDIA received FDA approval to reduce the risk of cardiovascular death, hospitalization for heart failure and urgent heart failure visits in adults with HF LVEF ≥40%.
Now, KERENDIA is also approved by the FDA to reduce UACR, which is expected to reduce the risk of sustained eGFR decline and end-stage kidney disease in adults with CKD associated with T1D.
Arowhead Pharmaceuticals Presents Phase 3 SHASTA-3 and SHASTA-4 Data Demonstrating Plozasiran Reduced Acute Pancreatitis Events in Patients with Severe Hypertriglyceridemia
On August 30, Arrowhead Pharmaceuticals, Inc., presented results from the pivotal Phase 3 SHASTA-3 and SHASTA-4 studies of plozasiran in adults with severe hypertriglyceridemia (sHTG) during a Hot Line Late-Breaking Science session at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany.
SHASTA-3 and SHASTA-4 met their primary and all prespecified secondary endpoints and demonstrated deep and durable reductions in triglycerides (TG), with median reductions from baseline of 79% and 81%, respectively at Month 12 (p<0.0001 in both studies). In a prespecified pooled analysis, plozasiran also significantly reduced acute pancreatitis (AP) events across the broad sHTG study population, with greater absolute benefit observed among patients at higher risk of AP. More than 90% of plozasiran-treated patients in both studies achieved TG levels below 500 mg/dL (<5.65 mmol/L) at Month 12, and more than half achieved TG levels below 150 mg/dL (<1.69 mmol/L).
“These SHASTA-3 and -4 results build on the compelling topline data we reported in July and further strengthen our view that plozasiran has the potential to fundamentally change how severe hypertriglyceridemia is treated,” said Christopher Anzalone, PhD, president and chief executive officer at Arrowhead. “The depth and consistency of triglyceride lowering across two large pivotal studies are impressive, but what may be most important for patients and physicians is the significant reduction in acute pancreatitis. The benefit was particularly pronounced among patients with a prior history of pancreatitis, a population with substantial ongoing risk. Combined with quarterly dosing and a favorable safety and tolerability profile, we believe these data demonstrate a highly differentiated profile for plozasiran and unequivocally support our plans to seek regulatory approval for the broader sHTG population. Our purchase of a U.S. FDA Priority Review Voucher, announced earlier this month, will potentially accelerate our goal of getting this important new medicine to patients.”
James Hamilton, MD, MBA, chief medical officer and Head of R&D at Arrowhead, added, “SHASTA-3 and SHASTA-4 enrolled a broad population that reflects the heterogeneity and substantial disease burden seen in patients with severe hypertriglyceridemia. Plozasiran produced deep and durable reductions in triglycerides and other atherogenic lipoproteins, and more than 90% of treated patients achieved triglyceride levels below the severe hypertriglyceridemia threshold at Month 12. Importantly, the reduction in acute pancreatitis events was observed across the pooled population and became increasingly more meaningful in patients at higher risk. We believe the totality of these data provides strong evidence supporting APOC3 reduction in the liver with plozasiran as a potentially important treatment approach for patients with sHTG.”
Arrowhead intends to leverage data from the Phase 3 SHASTA-3, SHASTA-4 and MUIR-3 studies to seek marketing authorization for plozasiran in the broader sHTG population in multiple global geographies, beginning with a planned supplemental New Drug Application (sNDA) with the U.S. Food and Drug Administration (FDA) before the end of 2026. On August 4, 2026, the company announced it had purchased an FDA Priority Review Voucher, which it intends to utilize for this application.
SHASTA-3 and SHASTA-4 Phase 3 Results
SHASTA-3 and SHASTA-4 were global, randomized, double-blind, placebo-controlled Phase 3 studies evaluating plozasiran 25 mg administered subcutaneously once every three months in adults with sHTG. Across the two studies, 757 patients were randomized to receive plozasiran or placebo.
In a prespecified pooled analysis of AP events from SHASTA-3 and SHASTA-4:
Plozasiran reduced the rate of all AP events by 78% versus placebo (RR 0.22; 95% CI: 0.07, 0.67; p=0.008), corresponding to a 4.1% absolute risk reduction and a number needed to treat to prevent one AP event over one year (NNT), of 24.
Plozasiran significantly reduced the risk of a first AP event (HR 0.26; 95% CI: 0.09, 0.78; p=0.016).
Among patients with TG ≥ 500 mg/dl (5.65 mmol/L) any prior history of AP, plozasiran reduced the AP event rate by 91% versus placebo (RR 0.09; 95% CI: 0.02, 0.41; p=0.002), corresponding to a 34% absolute risk reduction and NNT over one year, of 3.
Safety and Tolerability
Plozasiran demonstrated a favorable safety and tolerability profile in SHASTA-3 and SHASTA-4. Overall treatment-emergent adverse events (TEAEs) were reported in 73% of patients in both the pooled plozasiran and placebo groups. Serious TEAEs occurred in 8.3% of patients receiving plozasiran and 10% receiving placebo. TEAEs leading to study drug discontinuation were uncommon, occurring in 1.4% of plozasiran-treated patients and 0.8% of placebo-treated patients.
The most common TEAEs occurring in at least 5% of plozasiran-treated patients included worsening glycemic control (14.3%) and diarrhea (5.6%), compared with 8.7% and 3.2%, respectively, in placebo-treated patients. Despite the imbalance in reported glycemic control-related TEAEs, mean HbA1c showed minimal to modest absolute change from baseline with no worsening of mean HbA1c over time.
Injection-site reactions occurred in 3.2% of plozasiran-treated patients and 2.0% of placebo-treated patients. There were no cases of anaphylaxis or systemic hypersensitivity. No clinically meaningful changes in platelet counts or meaningful elevations in ALT or AST relative to placebo were observed, and no cases met Hy’s law criteria. In a prespecified MRI-PDFF sub study, there was no statistically significant treatment-emergent increase in hepatic fat fraction (p=0.70).
Three fatal events occurred in plozasiran-treated patients, consisting of two cardiovascular deaths and one death due to chronic myelomonocytic leukemia. All three were attributed to pre-existing cardiovascular or hematologic disease and assessed as unrelated to study treatment.
