NEJM Study Shows Positive Results of Sanofi’s Drug for Rare Blood Disorder

Rare Daily Staff

A study published in The New England Journal of Medicine showed positive results of the phase 3 trial of Cablivi, Sanofi’s treatment for adults with acquired thrombotic thrombocytopenic purpura, a rare, life-threatening autoimmune blood disorder.

Acquired thrombotic thrombocytopenic purpura (aTTP) is characterized by extensive clot formation in small blood vessels throughout the body, leading to very low platelet count, loss of red blood cells through destruction, 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, along with immunosuppression. Despite 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.

Cablivi stops the formation and accumulation of the micro-clots that cause the thrombocytopenia, tissue ischemia, and organ dysfunction in aTTP. Cablivi was developed by Ablynx, a Sanofi company.

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 U.S. Food and Drug Administration has accepted for priority review the application to market Cablivi in the United States for treatment of patients 18 years of age and older experiencing an episode of aTTP. The agency is expected to act by February 6.

The phase 3 randomized, double-blind, placebo-controlled study of Cablivi in patients with aTTP included 145 patients who were randomly assigned to Cablivi or placebo in conjunction with plasma exchange and immunosuppression.

The result show Cablivi significantly reduced the time to platelet count normalization. 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. During the overall study period, patients receiving Cablivi experienced a significantly lower number of aTTP recurrences (67 percent reduction) compared to placebo.

The study saw normalization of three organ-damage markers (lactate dehydrogenase, cardiac troponin I, and serum creatinine) occurred sooner in patients who received Cablivi versus placebo. Results also showed a clinically meaningful reduction in the use of plasma exchange in patients treated with Cablivi.

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 bleeding from the nose and gums.

“aTTP is a life-threatening disease, and the current treatment options do not fully halt the extensive clot formation in small blood vessels throughout the body, leaving patients at risk for significant morbidity and early death,” said Marie Scully, professor of hematology at University College London Hospitals, and lead author of the study. “These results demonstrate that Cablivi has the potential to address a major unmet medical need and to help those facing the potentially devastating consequences of this disorder.”

January 10, 2019
Photo: Marie Scully, professor of hematology at University College London Hospitals, and lead author of the study