Sanofi's Cablivi, the World’s First Nanobody Drug, Receives FDA Approval for Rare Thrombotic Disorder aTTP

Source:Bioon 2019-02-12 10:21

2019Year02Month12Daily News/BioValleyBIOON/ --French pharmaceutical giant Sanofi (Sanofi) recently announced that the U.S. Food and Drug Administration (FDA) Approved Nanobody DrugsCablivi（caplacizumab), combined with plasma exchange and immunosuppressive therapy, for acquired thrombotic thrombocytopenic purpura (aTTP) for the treatment of adult patients. This approval enablesCabliviThe first in the U.S. market specifically for treatingaTTPmedications.

CabliviSanofi's Massive Spending Spree48Acquire Belgian Biotech for Hundreds of Millions of US DollarsAblynxlater obtained, the drug was2018Year8Approved by the EU at the end of the month for use in patients who have previously undergone oneaTTPadult patients with episodes. This approval enablesCabliviBecame the first nanobody drug approved globally, and also the first specifically for the treatment ofaTTPdrugs. In the United States and the European UnionCabliviAll were granted treatmentaTTPorphan drug designation, and was granted Fast Track designation and Priority Review designation in the United States.

aTTPIt is a life-threatening, autoimmune-based coagulation disorder characterized by the formation of numerous blood clots in small vessels throughout the body, leading to severe thrombocytopenia (extremely low platelet count), microangiopathic hemolytic anemia (red blood cell loss due to hemolytic destruction), tissue ischemia (restricted blood supply to parts of the body), and extensive organ damage, particularly to the brain and heart. Despite receiving current standard care regimens, including once-daily plasma exchange (PEX) and immunosuppressive therapy, but patients still face a high risk of thrombotic complications, recurrence, and death,aTTPSeizures still occur in up to20%associated with mortality, with most deaths occurring after diagnosis30within days.

CabliviThe active pharmaceutical ingredient iscaplacizumab, a potent selective bivalent anti-von Willebrand factor (vWF) nanobodies, capable of blocking ultra-largevWFPolymer (ULvWF) interaction with platelets, targeting platelet aggregation and subsequent formation of microthrombi (microclot) has an immediate effect on the formation and accumulation. InaTTPIn patients, these microthrombi can lead to severe thrombocytopenia, tissue ischemia, and organ dysfunction.Cablivisuch instantaneous effects (immediate effect, i.e., immediate effect) while deconstructing the underlying disease process, it can protectaTTPThe patient presents with clinical manifestations of the disease.

Cablivi's approval is based onIIIPhase I Clinical StudyHERCULES（NCT02553317) data. This study was a randomized, double-blind, placebo-controlled trial that enrolled a total of145ExampleaTTPAdult patients. In the study, patients were randomly assigned toCablivior placebo, while receiving the standard of care (plasmapheresis and immunosuppressive therapy).

The research results show: (1) In terms of the primary endpoint, compared with placebo+Compared with the standard care regimen,CabliviThe combined standard care regimen significantly shortened the time to normalization of platelet count (p=0.01); at any specific time point during the study period,CabliviThe likelihood of the treatment group achieving a normal platelet count was that of the placebo group.1.55times. (2) Throughout the study period, compared with placebo+Compared with the standard care regimen,CabliviCombined Standard Care ProtocolaTTPRelated deaths,aTTPSignificant Reduction in Recurrence or at Least One Major Thromboembolic Event74%（p＜0.001）。（3) throughout the study period, compared with placebo+Compared with the standard care regimen,CabliviCombined Standard Care ProtocolaTTPSignificantly Reduced Recurrence Rate67%（p＜0.001）。（4) throughout the study period,CabliviTreatment group experienced0cases of refractory disease, occurred in the placebo group3cases of refractory disease, although no statistically significant difference was observed (p=0.06）。（5) Compared with the placebo group,CabliviPatients in the treatment group3Organ injury markers (lactate dehydrogenase, cardiac troponinI, serum creatinine) normalized earlier (due to stratified statistical testing,p(no significance detected). (6) Compared with the placebo group,CabliviThe use of plasma exchange in the treatment group showed a clinically significant reduction (mean5.8Dayvs 9.4Days, reduced38%), and in the intensive care unit (reducing65%) and hospitals (reduce31%) Shorter residence time. (7）CabliviThe safety profile was consistent with previous reports and aligned with its mechanism of action, including an increased risk of bleeding; the most common bleeding-related adverse events were epistaxis and gingival bleeding.

HERCULESChief Investigator of the Study, Professor of Haematology at University College London HospitalsMarie ScullyPreviously stated, “aTTPis a life-threatening disease. Current treatment regimens cannot completely prevent widespread thrombosis in systemic small vessels, thereby exposing patients to the risk of severe morbidity and premature death. Our research demonstrates thatCablivi"has the potential to address significant unmet medical needs in this field and help patients facing potentially devastating consequences." (Bioon)Bioon.com）

Original Source:Sanofi: FDA approves Cablivi? (caplacizumab-yhdp), the first Nanobody?-based medicine, for adults with acquired thrombotic thrombocytopenic purpura (aTTP)