Sanofi on Tuesday announced results from the Phase III CARDINAL study at the American Society of Hematology (ASH) annual meeting, with data showing that sutimlimab significantly boosted haemoglobin levels in patients with primary cold agglutinin disease. The company noted that the experimental C1s inhibitor could potentially become the first approved therapy for the disorder, with global R&D head John Reed saying "we are eager to share these results with regulatory authorities beginning with the…FDA" in the first quarter of 2020, possibly leading to clearance in the third quarter.
In the trial, 24 adults with cold agglutinin disease who received a recent blood transfusion were administered a fixed weight-based dose of sutimlimab via intravenous infusion on day zero, day seven and then once every other week up to week 26. The study's main goal was a responder rate based on a composite of an increase in haemoglobin of at least 2 g/dL from baseline or reaching a haemoglobin level of at least 12 g/dL at the 26-week treatment assessment timepoint and the absence of transfusions from weeks five to 26.
Results showed that 54% of patients met the composite endpoint criteria, while 62.5% of subjects achieved a haemoglobin level of at least 12 g/dL or an increase of at least 2 g/dL and 71% of participants remained transfusion-free after week five. The study showed an overall mean increase in haemoglobin of 2.6 g/dL at the treatment assessment timepoint, with 83% of patients achieving a significant mean haemoglobin improvement of at least 1 g/dL.
Sanofi said haemoglobin improved rapidly, with a mean increase from baseline of at least 1 g/dL by week one and at least 2 g/dL by the third week, after which levels were maintained at over 11 g/dL, "demonstrating a sustained effect throughout the remainder of the treatment period." Furthermore, total bilirubin reached near normal levels after the first week of treatment, with normalised levels remaining steady from the third week onward.
In terms of safety, Sanofi noted that 22 patients experienced one or more treatment-emergent adverse events. In addition, seven patients suffered at least one treatment-emergent serious adverse event (TESAE), while two had at least one TESAE of infection, although none of these were considered to be related to sutimlimab. Further, no patient discontinued sutimlimab due to infection and there were no meningococcal infections reported.
Sanofi acquired sutimlimab, previously known as TNT009 and BIVV009, last year through the $11.6-billion takeover  of Bioverativ. The drug has been granted breakthrough therapy status by the FDA for cold agglutinin disease, and has also received orphan drug designations from regulators in the US, Europe and Japan. Aside from CARDINAL, sutimlimab is being investigated in the Phase III CADENZA trial  of patients with primary cold agglutinin disease who have not recently had a blood transfusion. Sutimlimab is also in early-stage testing as a potential treatment for immune thrombocytopaenic purpura, with a Phase III study in this indication expected to begin in the first half of 2021.
For additional analysis, see ViewPoints: Sanofi's complement win adds to its orphan supplement plan .