Grifols’ BT524 Fibrinogen Therapy Shows Promise in Phase 3 Trial Published in The Lancet’s eClinicalMedicine
Grifols, a globally recognized healthcare company and a leader in the production of plasma-derived therapies, has marked a significant advancement in the treatment of acquired fibrinogen deficiency (AFD). The company recently announced the publication of positive Phase 3 clinical trial results for its investigational fibrinogen concentrate, BT524, in eClinicalMedicine, a prestigious peer-reviewed medical journal that is part of The Lancet Discovery Science Suite.
This milestone publication adds scientific credibility to Grifols’ ongoing research and regulatory efforts, potentially setting the stage for a new standard of care in managing bleeding episodes associated with low fibrinogen levels, particularly in surgical settings.
The Clinical Context: Understanding Acquired Fibrinogen Deficiency and BT524
Acquired fibrinogen deficiency is a condition where the body lacks sufficient levels of fibrinogen, a vital plasma protein produced by the liver. Fibrinogen plays an essential role in the coagulation cascade by facilitating blood clot formation and aiding in wound healing. During events such as major surgeries, trauma, or postpartum hemorrhage, patients may experience critically low levels of fibrinogen, compromising the body’s ability to control bleeding.
Traditionally, clinicians have addressed AFD with standard-of-care treatments such as fresh frozen plasma (FFP) or cryoprecipitate, both of which are blood products containing varying and often unpredictable concentrations of fibrinogen. These treatments also carry logistical and safety challenges, including blood type compatibility requirements, thawing delays, and risk of pathogen transmission.
Grifols’ BT524, developed by its subsidiary Biotest, offers a more standardized and potentially safer alternative. BT524 is a lyophilized, virus-inactivated fibrinogen concentrate that can be reconstituted and administered rapidly, ensuring a more controlled delivery of the needed clotting protein.
Phase 3 Trial Overview and Design
The pivotal Phase 3 clinical trial was designed to evaluate the efficacy and safety of BT524 compared to traditional therapies in patients with acquired fibrinogen deficiency undergoing elective major spinal or abdominal surgery. These procedures typically carry a high risk of bleeding, making them ideal scenarios to test interventions aimed at managing hemorrhage effectively.
The trial’s primary objective was to demonstrate that BT524 is non-inferior to the current standard of care—namely, cryoprecipitate or fresh frozen plasma—in reducing intraoperative blood loss. The study employed a randomized, controlled design, enrolling patients across multiple clinical sites in Europe.
Key Results: Non-Inferiority Demonstrated with Added Safety Benefits
The trial met its primary endpoint, confirming that BT524 is non-inferior to FFP/cryoprecipitate in reducing clinically significant intraoperative bleeding. According to the published results, the adjusted mean volume of blood loss during surgery was 1,381 mL (95% confidence interval [CI]: 1,187–1,574) in the BT524 group, compared to 1,660 mL (95% CI: 1,461–1,860) in the FFP/cryoprecipitate group. This translates into a mean difference of 279 mL in favor of BT524, demonstrating its effective hemostatic function.
But beyond efficacy, BT524 also stood out for its safety profile. Notably, the treatment group experienced a statistically significant lower incidence of thromboembolic events (TEEs), a common and serious complication associated with procoagulant therapies. This reduced risk could make BT524 a more attractive option in high-risk surgical patients or those with underlying cardiovascular issues.
Expert Perspectives: Clinical Significance and Future Implications
Dr. Jörg Schüttrumpf, Chief Scientific Innovation Officer at Grifols, emphasized the significance of this publication in advancing bleeding management. “The trial results, now featured in this prestigious clinical medicine journal, support the potential of BT524 to be considered for patients with clinically relevant uncontrolled bleeding,” he said. “We look forward to finalizing regulatory approval processes in Europe and the United States as soon as possible.”
The company’s plans to pursue regulatory approvals on both sides of the Atlantic suggest that BT524 may soon become a viable commercial option, pending review by agencies such as the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA). If approved, BT524 would strengthen Grifols’ existing portfolio of hemostatic and critical care therapies and offer clinicians a highly purified, reliable, and easy-to-administer fibrinogen replacement option.
Niels Rahe-Meyer, M.D., the lead clinical investigator for the study and a specialist at Hannover Medical School’s Department of Anesthesiology and Intensive Care Medicine in Germany, echoed the sentiment. “We look forward to sharing the results of the AdFIrst study more broadly with the medical community as part of the research publication and at ISTH,” he said, referring to the upcoming International Society on Thrombosis and Haemostasis (ISTH) meeting. “These data could represent a breakthrough in our understanding of hemorrhage management with fibrinogen.”
The AdFIrst (Acquired Fibrinogen Deficiency Intervention First) trial now serves as a cornerstone for BT524’s clinical development program and could redefine transfusion protocols in surgeries where bleeding is anticipated.
The Advantages of Fibrinogen Concentrates Over Conventional Blood Products
One of the key reasons BT524 is generating enthusiasm in the hematology and surgery communities is its potential to address the limitations of traditional therapies. Cryoprecipitate, while rich in fibrinogen, has variable potency, is pooled from multiple donors, and requires freezing, thawing, and compatibility checks. Fresh frozen plasma is similarly logistically complex and contains lower concentrations of fibrinogen.
In contrast, BT524 offers:
- Standardized dosing: Each vial contains a precisely measured amount of fibrinogen, reducing variability.
- Improved safety: The product undergoes viral inactivation and purification processes.
- Rapid reconstitution: Allows timely administration in urgent situations.
- No blood type matching: Simplifies logistics and enables universal administration.
Such attributes are especially beneficial in emergency settings like trauma centers, operating rooms, and intensive care units where rapid and reliable control of bleeding is essential.
Regulatory Outlook and Commercial Potential
With positive Phase 3 data in hand and peer-reviewed publication now achieved, Grifols is in a strong position to engage regulatory authorities. The company has not yet specified a timeline for submissions, but statements from executives indicate that filings with the EMA and FDA are imminent.
If approved, BT524 could compete directly with other fibrinogen concentrates already available in certain markets, such as RiaSTAP (CSL Behring). However, BT524’s robust data from a controlled Phase 3 study may give it an edge, especially if supported by real-world evidence post-launch.
Moreover, the market for fibrinogen therapies is expected to expand. As surgical practices evolve and awareness of fibrinogen’s role in bleeding control grows, demand for faster, safer, and more predictable fibrinogen supplementation is likely to increase.
A Potential Breakthrough in Hemostasis
Grifols’ latest announcement and the associated eClinicalMedicine publication represent a pivotal moment in the development of BT524 and in the broader field of hemostatic therapies. The successful Phase 3 trial not only confirms the clinical utility of BT524 but also introduces a potentially superior option for managing acquired fibrinogen deficiency in surgical patients.
As Grifols prepares to move into the regulatory phase, the medical community will be closely watching for approval decisions and additional clinical data. Should BT524 receive the green light, it could revolutionize bleeding management protocols and offer new hope to patients facing complex surgeries with high bleeding risks. In doing so, Grifols reaffirms its leadership in plasma-derived innovations and its commitment to advancing patient care through scientific excellence.
