Grifols subsidiary Biotest has achieved a significant regulatory milestone with positive topline results from its AdFIrst phase 3 clinical trial evaluating fibrinogen concentrate BT524 for acquired fibrinogen deficiency (AFD), positioning the treatment for potential approval in a global market estimated at USD 800 million.
The prospective, active-controlled, multicenter phase 3 trial met its primary endpoint, demonstrating that BT524 is non-inferior to standard of care in reducing intraoperative blood loss in patients with acquired fibrinogen deficiency undergoing planned major spinal or abdominal surgery. Mean blood loss measured 1,444 mL in the BT524 group versus 1,735 mL in the standard of care group, resulting in a 291 mL reduction in patients treated with fibrinogen concentrate.
Clinical Trial Design and Results
The AdFIrst (Adjusted Fibrinogen Replacement Strategy) trial randomized patients with high blood loss during planned spinal or abdominal surgery 1:1 to treatment with BT524 or cryoprecipitate/fresh frozen plasma (FFP). The study evaluated efficacy by comparing further blood loss between both treatment options while maintaining an excellent safety profile for the fibrinogen concentrate.
"This successful clinical trial is a significant stride towards a potential therapy that could contribute to the care of patients who experience severe blood loss during major surgery," said Jörg Schüttrumpf, Grifols Chief Scientific Innovation Officer.
Addressing Unmet Medical Need
Acquired fibrinogen deficiency typically occurs during surgical procedures when there's insufficient fibrinogen to arrest bleeding. Current standard treatments include cryoprecipitate or fresh frozen plasma, both containing fibrinogen but also other unnecessary proteins and elements, requiring large volumes to ensure adequate fibrinogen levels. Additionally, both treatments need to be thawed in advance, which is time-consuming when lives are at risk.
Fibrinogen concentrate represents a precision medicine approach, allowing patients on the operating table to immediately receive only what's essential to curtail hemorrhaging. The defined amount of fibrinogen in the concentrate enables tailor-made, patient-specific and highly effective therapy.
Regulatory Timeline and Market Potential
BT524 will likely enter regulatory authorization processes in Q4 2024, starting in Europe and the United States. If approved, it would be the first fibrinogen concentrate approved for an AFD indication in the U.S., targeting a global market with an estimated potential of USD 800 million.
Fibrinogen, a plasma protein produced in the liver, plays a key role in stopping blood loss and wound healing. Grifols' experience with fibrinogen to manage surgical bleeding includes a fibrinogen-based fibrin sealant launched five years ago.
Strategic Innovation Impact
"The positive results for Biotest's fibrinogen are an important milestone and strengthen a Grifols innovation strategy that's diversified across plasma and non-plasma, balanced between internal and external investments, and includes both shorter- and longer-term development cycles," said Victor Grifols Deu, Grifols Chief Operating Officer.
The advancement of BT524 occurs alongside other Biotest innovations contributing to Grifols' growth. Biotest's immunoglobulin Yimmugo entered the European market in late 2022 and awaits U.S. authorization, while trimodulin, a polyvalent immunoglobulin with IgM, IgA and IgG, is currently in two phase 3 clinical trials for community-acquired pneumonia and severe community-acquired pneumonia.
Biotest has also developed the fibrinogen concentrate for congenital fibrinogen deficiency, completing a multinational phase I/III study in patients with this condition. Based on results from both successful clinical trials, Biotest has applied to the EMA and FDA for approval of fibrinogen concentrate for treatment of patients with both congenital and acquired fibrinogen deficiency.
Detailed results of the AdFIrst trial will be presented later this year.
