NEJM reports positive phase III trial of Cablivi to treat thrombocytopenic purpura.- Sanofi

The New England Journal of Medicine (NEJM) published positive results of the Phase III trial of Cablivi (nejm ) in adults with acquired thrombotic thrombocytopenic purpura (aTTP). aTTP is a rare, life-threatening autoimmune blood disorder characterized by extensive clot formation in small blood vessels throughout the body, leading to severe thrombocytopenia (very low platelet count), microangiopathic hemolytic anemia (loss of red blood cells through destruction), ischemia (restricted blood supply to parts of the body) and widespread organ damage, especially in the brain and heart.

The current treatment for aTTP consists of daily plasma exchange, in which a patient's blood plasma is removed and replaced with donor plasma, and immunosuppression. Even with currently available treatments, patients continue to be at risk of developing acute blood clotting conditions, such as stroke and heart attack, as well as recurrence of disease.

Key findings of the HERCULES Phase III study of Cablivi include: On the primary endpoint, Cablivi significantly reduced the time to platelet count normalization (p=0.01). At any given time point during the study, patients receiving Cablivi were 1.55 times more likely to achieve normal platelet counts than patients on placebo. Treatment with Cablivi was associated with a 74 percent reduction in aTTP-related death, recurrence of aTTP, or at least one major thromboembolic event compared with placebo (p<0.001). during the overall study period patients receiving cablivi experienced a significantly lower number of attp recurrences 67 percent reduction compared to placebo p><0.001). refractory disease developed in 0 patients in the cablivi group versus 3 patients in the placebo group although this did not reach statistical significance p="0.06)." normalization of three organ-damage markers lactate dehydrogenase cardiac troponin i and serum creatinine occurred sooner in patients who received caplacizumab versus placebo p not tested due to hierarchical statistical testing. results showed a clinically meaningful reduction in the use of plasma exchange in patients treated with cablivi average 5.8 days 38 percent reduction versus placebo 9.4 days as well as a shorter stay in the intensive care unit 65 percent reduction and hospital 31 percent reduction.>

Cablivi demonstrated a safety profile consistent with what has been previously reported and in line with its mechanism of action; this included an increased risk of bleeding. The most frequently reported bleeding-related adverse events were epistaxis and gingival bleeding. HERCULES is a Phase III randomized, double-blind, placebo-controlled study of Cablivi in patients with aTTP. In the study, 145 patients were randomly assigned to Cablivi or placebo in conjunction with plasma exchange and immunosuppression.

Comment: Cablivi was approved by the European Commission in August 2018 for the treatment of adults experiencing an episode of aTTP. It is the first therapeutic specifically indicated for the treatment of aTTP. Additionally, the FDA has accepted for priority review the Biologics License Application for Cablivi for treatment of patients 18 years of age and older experiencing an episode of aTTP. The target action date for the FDA decision is February 6, 2019.

See--Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura"- DOI: 10.1056/NEJMoa1806311., Paul Coppo, M.D., Ph.D., Paul Kn�bl, M.D., et al., for the HERCULES Investigators-January 9, 2019 DOI: 10.1056/NEJMoa1806311.