Sanofi's Cablivi, the World’s First Nanobody Drug, Approved in Canada for Acquired Thrombotic Thrombocytopenic Purpura (aTTP)

March 5, 2020 News /BioValleyBIOON/ -- Sanofi recently announced that Health Canada has approved through the Priority Review pathwayNanoCablivi (caplacizumab), an antibody drug, in combination with plasma exchange and immunosuppressive therapy, is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP). aTTP is a rare blood disorder that causes blood clots to form in small vessels throughout the body, potentially leading to damage to vital organs and life-threatening complications. Cablivi is the first drug specifically approved in Canada for the treatment of aTTP.

Cablivi is the first globally approvedNanoAntibody drug, and also the first drug specifically for the treatment of aTTPCablivi prevents the formation of microthrombi (blood clots) in the body, enabling faster patient recovery, reducing some complications associated with aTTP, and lowering the rate of disease recurrence.。

Cablivi was developed by the Belgian biotechnology company Ablynx, which Sanofi acquired in January 2018 for $4.8 billion. Cablivi received approval in the European Union in August 2018 and in the United States in February 2019. In both the US and the EU, Cablivi was granted orphan drug designation for the treatment of aTTP, and in the US, it also received Fast Track designation and Priority Review status. Currently, Cablivi is part of the rare hematology franchise under Sanofi Genzyme, the global specialty care business unit of Sanofi.

aTTP is a life-threatening, based onAutoimmunitycoagulation disorder characterized by the formation of numerous blood clots in small vessels throughout the body, leading to severe thrombocytopenia (extremely low platelet count) and microangiopathic hemolyticAnemia(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-of-care regimens, including once-daily plasma exchange (PEX) and immunosuppressive therapy, patients remain at high risk for thrombotic complications, relapse, and death; acute thrombotic thrombocytopenic purpura (aTTP) episodes are still associated with a mortality rate of up to 20%, with most deaths occurringDiagnosisWithin the following 30 days.

Cablivi’s active pharmaceutical ingredient is caplacizumab, a potent, selective bivalent anti-von Willebrand factor (vWF)NanoThe antibody, which blocks the interaction between ultra-large von Willebrand factor (ULvWF) multimers and platelets, has an immediate effect on inhibiting platelet aggregation and the subsequent formation and accumulation of microclots. In patients with acquired thrombotic thrombocytopenic purpura (aTTP), these microclots can lead to severe thrombocytopenia, tissue ischemia, and organ dysfunction. Cablivi’s immediate effect (i.e., instant efficacy) helps dismantle the underlying disease process while protecting aTTP patients from developing clinical manifestations of the disease.

The approval of Cablivi was based on data from the Phase III clinical study HERCULES (NCT02553317). This study was a randomized, double-blind, placebo-controlled trial that enrolled a total of 145 adult patients with acquired thrombotic thrombocytopenic purpura (aTTP). In the study, patients were randomly assigned to receive either Cablivi or placebo, in addition to standard of care (plasma exchange and immunosuppressive therapy).

Study results showed: (1) For the primary endpoint, compared with placebo plus standard of care, Cablivi combined with standard of care significantly shortened the time to platelet count normalization (p=0.01); at any specific time point during the study, patients in the Cablivi group were 1.55 times more likely to achieve normal platelet counts than those in the placebo group. (2) Throughout the study period, compared with placebo plus standard of care, Cablivi combined with standard of care significantly reduced aTTP-related death, aTTP recurrence, or at least one major thromboembolic event by 74% (p<0.001). (3) Throughout the study period, compared with placebo plus standard of care, Cablivi combined with standard of care significantly reduced the number of aTTP recurrences by 67% (p<0.001). (4) Throughout the study period, there were 0 cases of refractory disease in the Cablivi group and 3 cases in the placebo group, although this difference did not reach statistical significance (p=0.06). (5) Compared with the placebo group, patients in the Cablivi group experienced earlier normalization of three markers of organ damage (lactate dehydrogenase, cardiac troponin I, and serum creatinine) (p-values for significance were not assessed due to hierarchical statistical testing). (6) Compared with the placebo group, the Cablivi group showed a clinically meaningful reduction in the use of therapeutic plasma exchange (mean 5.8 days vs. 9.4 days, a 38% reduction) and shorter stays in the intensive care unit (65% reduction) and hospital (31% reduction). (7) The safety profile of Cablivi 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. (Bioon.com)

Original Source: Cablivi (caplacizumab)approved by Health Canada for adults living with acquired thrombotic thrombocytopenic purpura (aTTP)