Talphera's nafamostat gains KDIGO endorsement as NEPHRO CRRT trial nears completion
核心洞察
Talphera's Phase 3 NEPHRO CRRT study of nafamostat (Niyad (搜索)) has reached 75% enrollment of its 70-patient target, with completion expected by year-end 2026.
The draft 2026 KDIGO guidelines now cite nafamostat as an acceptable regional anticoagulant during CRRT, a positive change from prior recommendations.
Updated market research projects roughly 200,000 U.S. CRRT procedures in 2027, a 21% increase over prior estimates.
Talphera, Inc. (搜索) (Nasdaq: TLPH) has reached 75% enrollment in its Phase 3 registrational NEPHRO CRRT study of nafamostat (branded Niyad (搜索)), keeping the company on track for study completion by year-end 2026. The trial, which targets 70 adult patients undergoing continuous renal replacement therapy (CRRT), has now activated all 14 U.S. intensive care unit sites following a site realignment that had previously slowed momentum. With completion expected before year-end, a regulatory package could begin taking shape as soon as early 2027.
The more consequential development this quarter, however, lies outside the enrollment scoreboard. The draft 2026 KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for acute kidney injury (搜索) (AKI) and acute kidney disease (搜索) (AKD) now cite nafamostat as an acceptable regional anticoagulant during CRRT, a meaningful upgrade from prior language that offered no such endorsement. KDIGO guidance shapes clinical practice globally, and its inclusion of nafamostat before U.S. approval creates a form of pre-legitimacy that most drug developers spend years and millions trying to manufacture through medical affairs programs.
"Reaching 75% enrollment in the NEPHRO CRRT study keeps us on track for completion by year-end," stated Vince Angotti, CEO of Talphera. "Site realignment is complete, with all target clinical sites now activated. We are particularly pleased with the high level of engagement from our principal investigators and study site personnel."
Angotti further noted that the KDIGO 2026 Clinical Practice Guideline for AKI and AKD is currently pending final publication following the close of its public comment period in May, and that the guideline references nafamostat as an acceptable regional anticoagulant during CRRT — a positive change from KDIGO's last published AKI guidelines.
Unmet Need in CRRT Anticoagulation
Anticoagulation during CRRT remains a clinically managed problem. Citrate (搜索) received only an Emergency Use Authorization for use as a replacement solution during COVID-era shortages, while heparin carries well-documented bleeding risks in the critically ill patients this trial specifically targets — those who cannot tolerate heparin or are at elevated bleeding risk.
Nafamostat is a broad-spectrum, synthetic serine protease inhibitor with anticoagulant, anti-inflammatory and potential anti-viral activities. Niyad (搜索) is a lyophilized formulation of nafamostat currently being studied under an investigational device exemption (IDE) as an anticoagulant for the extracorporeal circuit, and it has received Breakthrough Device Designation status from the U.S. Food and Drug Administration (FDA).
Trial Design and Endpoints
The NEPHRO CRRT study is designed as a prospective, double-blinded trial conducted at up to 14 U.S. hospital intensive care units. It will enroll and evaluate 70 adult patients undergoing renal replacement therapy who cannot tolerate heparin or are at risk for bleeding.
The primary endpoint is mean post-filter activated clotting time using Niyad (搜索) versus placebo over the first 24 hours. Key secondary endpoints include the mean post-filter activated clotting time over 72 hours, filter lifespan, number of filter changes over 72 hours, number of transfusions over 72 hours, and dialysis efficacy (based on urea concentration) over the first 24 hours.
The trial's small, tightly scoped design with a device-style approach carries real regulatory efficiency, but it also concentrates risk. If the clotting-time endpoint does not translate cleanly into a compelling filter-lifespan or dialysis-efficacy story in the secondary data, the commercial narrative could become complicated quickly. The single endpoint most likely to determine whether nephrologists and intensivists actually change practice is filter lifespan across the 72-hour secondary window.
Market Opportunity and Financial Position
Talphera revised its addressable market estimate upward, projecting roughly 200,000 U.S. CRRT procedures in 2027, a 21% increase over the company's prior figures. An ICD-10 procedural code, XY0YX37, has been issued for the extracorporeal introduction of nafamostat, providing a specific and billable code to indicate the procedure.
The company reported cash and investments of $17.1 million as of June 30, 2026. Combined R&D and SG&A expenses for the second quarter of 2026 totaled $3.9 million, compared to $3.7 million for the second quarter of 2025, with the increase primarily driven by higher Niyad (搜索) development expenses reflecting increased enrollment. Net loss attributable to common shareholders for the second quarter of 2026 was $4.3 million, or $0.06 per basic and diluted share, compared to a net loss of $3.5 million, or $0.10 per basic and diluted share, for the second quarter of 2025.
Talphera also regained Nasdaq compliance with the $1 bid price rule. The company plans to host an investor event as enrollment nears completion to share these findings and discuss the commercial opportunity for nafamostat, if approved, including the potential favorable implications of the evolving KDIGO guidelines.