The landscape of endocrine and renal medicine underwent a significant shift this week as two major pharmaceutical developments reached critical milestones. Bayer announced that the U.S. Food and Drug Administration (FDA) has granted approval for KERENDIA (finerenone) as the first new treatment in three decades for adults with chronic kidney disease (CKD) associated with type 1 diabetes (T1D). Simultaneously, Arrowhead Pharmaceuticals presented late-breaking Phase 3 data for plozasiran, a therapeutic candidate that demonstrated a substantial reduction in both triglycerides and the incidence of acute pancreatitis in patients with severe hypertriglyceridemia (sHTG). These developments address long-standing unmet needs in patient populations that have historically faced limited therapeutic options and high risks of organ failure or life-threatening inflammatory events.
Bayer’s KERENDIA: A Historic Shift in Type 1 Diabetes Management
On September 17, Bayer confirmed that the FDA approved a supplemental New Drug Application (sNDA) for KERENDIA, marking the first time in over 30 years that a new pharmacological intervention has been authorized specifically to address the progression of chronic kidney disease in the type 1 diabetes population. The approval is specifically indicated to reduce the urinary albumin-to-creatinine ratio (UACR) in adult patients. By lowering UACR, a key biomarker of renal stress and damage, the treatment is expected to mitigate the risk of sustained decline in the estimated glomerular filtration rate (eGFR) and the eventual onset of end-stage kidney disease (ESKD).
The FDA’s decision was facilitated through a Priority Review designation, a status reserved for drugs that offer significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. This regulatory acceleration underscores the urgency of the clinical need; while type 2 diabetes has seen a surge in new renal-protective therapies such as SGLT2 inhibitors over the last decade, the type 1 population has largely remained dependent on decades-old standard-of-care treatments, primarily ACE inhibitors and ARBs.
The FINE-ONE Clinical Trial and Evidence Base
The approval was underpinned by results from the FINE-ONE trial (NCT05901831), a pivotal, global, Phase 3 study. This randomized, double-blind, placebo-controlled multicenter trial enrolled 242 adult participants with CKD associated with T1D. The primary objective was to evaluate whether KERENDIA, administered at doses of 10 mg or 20 mg once daily, could outperform a placebo in reducing UACR over a six-month period when added to the existing standard of care.
Data presented at the American Society of Nephrology (ASN) Kidney Week 2025 and subsequently published in the New England Journal of Medicine revealed that KERENDIA met its primary endpoint with statistical significance. The trial demonstrated that reducing UACR is a viable surrogate for long-term kidney protection in this specific demographic. This "bridging" strategy allowed researchers to apply the established cardiovascular and renal outcome evidence from KERENDIA’s previous trials in type 2 diabetes (the FIDELIO-DKD and FIGARO-DKD studies) to the type 1 patient group.
Clinical Implications for Patients and Physicians
For decades, the medical community has struggled with the "residual risk" of kidney failure in T1D patients despite optimal blood pressure and glucose control. Dr. Janet McGill, Professor of Medicine at Washington University School of Medicine and Co-Chair of the study’s Executive Committee, noted that the approval represents a turning point for a population that has been clinically underserved. The ability of KERENDIA to function as a non-steroidal mineralocorticoid receptor antagonist (MRA) allows it to block the overactivation of the mineralocorticoid receptor, which is known to contribute to inflammation and fibrosis in the kidneys and heart.
Unlike older steroidal MRAs, KERENDIA exhibits a higher selectivity and a different distribution between the heart and kidneys, which may offer a more favorable safety profile regarding electrolyte imbalances like hyperkalemia. With this latest approval, KERENDIA is now the only MRA indicated for adults with CKD associated with both type 1 and type 2 diabetes, as well as for certain types of heart failure.
Arrowhead Pharmaceuticals: Plozasiran’s Impact on Severe Hypertriglyceridemia
In a parallel development within the lipidology sector, Arrowhead Pharmaceuticals presented groundbreaking results from its Phase 3 SHASTA-3 and SHASTA-4 clinical trials. The data, showcased during a "Hot Line" late-breaking session at the European Society of Cardiology (ESC) Congress 2026 in Munich, focused on plozasiran, an investigational RNA interference (RNAi) therapeutic designed to reduce the production of Apolipoprotein C-III (APOC3).
Severe hypertriglyceridemia, defined as triglyceride levels exceeding 500 mg/dL, carries a significant risk of acute pancreatitis (AP), a painful and potentially fatal inflammation of the pancreas. Current treatments often fail to lower triglycerides sufficiently to eliminate this risk, leaving patients in a state of constant medical vulnerability.
Analysis of SHASTA-3 and SHASTA-4 Results
The SHASTA-3 and SHASTA-4 studies were global, double-blind trials evaluating a 25 mg dose of plozasiran administered subcutaneously once every three months. The trials involved 757 patients and achieved their primary and all prespecified secondary endpoints with high statistical significance (p<0.0001).
Key findings from the data include:
- Triglyceride Reduction: Patients treated with plozasiran experienced median reductions in triglycerides of 79% and 81% at the 12-month mark.
- Target Achievement: Over 90% of patients achieved triglyceride levels below the 500 mg/dL threshold, and more than half reached levels below 150 mg/dL, which is considered within the normal range.
- Pancreatitis Risk Mitigation: A pooled analysis showed that plozasiran reduced the rate of all acute pancreatitis events by 78% compared to the placebo group.
- High-Risk Population Benefit: Among patients with a prior history of AP and baseline triglycerides above 500 mg/dL, the treatment reduced the event rate by 91%. In this high-risk group, the "number needed to treat" (NNT) to prevent one pancreatitis event over one year was remarkably low, at just three patients.
Safety and Regulatory Pathway
The safety profile of plozasiran was reported as favorable, with treatment-emergent adverse events (TEAEs) being comparable between the drug and placebo groups (73%). While there was a slight imbalance in reports of worsening glycemic control (14.3% in the treatment group vs. 8.7% in the placebo group), mean HbA1c levels showed no significant worsening over time. Importantly, there were no clinically meaningful changes in platelet counts or liver enzymes, and no cases of systemic hypersensitivity were recorded.
Christopher Anzalone, PhD, CEO of Arrowhead, emphasized that the consistency of the data across two large pivotal studies supports the company’s plan to seek broad regulatory approval. Arrowhead has already purchased an FDA Priority Review Voucher for $150 million, intending to use it to accelerate the review process for plozasiran. The company expects to file a supplemental New Drug Application (sNDA) before the end of 2026.
Chronology of Therapeutic Progress
To understand the weight of these announcements, it is essential to view them within the timeline of recent pharmaceutical history:
- 2021: KERENDIA receives its first FDA approval for CKD associated with type 2 diabetes, based on the FIDELIO-DKD trial.
- July 2025: KERENDIA’s indication is expanded to include the reduction of cardiovascular death and hospitalization in patients with heart failure (LVEF ≥40%).
- August 2026: Arrowhead presents the SHASTA Phase 3 data at the ESC Congress, proving the efficacy of APOC3 inhibition.
- September 2026: Bayer announces the landmark approval for KERENDIA in type 1 diabetes, ending a 30-year drought in new therapies for this indication.
- Late 2026 (Projected): Arrowhead plans to submit plozasiran for FDA approval using a Priority Review Voucher.
Broader Medical and Economic Implications
The emergence of these therapies reflects a broader trend in medicine toward precision targeting—whether through non-steroidal receptor antagonism in the case of Bayer or RNA interference in the case of Arrowhead.
For the healthcare system, the implications of these approvals are twofold: clinical and economic. Chronic kidney disease and acute pancreatitis are among the most expensive conditions to manage. The progression of CKD to end-stage kidney disease necessitates dialysis or transplantation, both of which carry immense costs and significantly reduced quality of life. By providing a tool to slow this progression in T1D patients, KERENDIA could potentially save the healthcare system billions in long-term care costs.
Similarly, the reduction in acute pancreatitis hospitalizations offered by plozasiran addresses a high-acuity medical need. The data suggesting an NNT of 3 for high-risk patients is particularly striking to health economists, as it indicates a highly efficient intervention for preventing emergency room visits and intensive care admissions.
As these drugs move into standard clinical practice, the focus will shift to implementation and access. For physicians, the challenge will be identifying patients early enough in their disease progression to maximize the protective benefits of these new agents. For patients, these developments represent more than just new prescriptions; they represent a significant reduction in the "disease burden" and a measurable increase in the hope for long-term organ preservation and stability.
