Rare Daily Staff

The U.S. Food and Drug Administration has approved Sanofi’s Cablivi in combination with plasma exchange and immunosuppression for the treatment of the rare blood-clotting disorder acquired thrombotic thrombocytopenic purpura (aTTP) in adults.

Cablivi is the first FDA approved therapy specifically indicated for the treatment of aTTP, a rare, life-threatening, autoimmune disorder. Despite the current standard-of-care treatment, consisting of daily plasma exchange and immunosuppression, episodes of aTTP are still associated with a mortality rate of up to 20 percent, with most deaths occurring within 30 days of diagnosis. The European Commission approved Cablivi in August 2018.

Cablivi is the company’s first Nanobody-based medicine to receive approval and the first newly approved product that will be part of Sanofi Genzyme’s Rare Blood Disorders franchise. Ablynx, which Sanofi acquired in 2018, developed Cablivi. It targets von Willebrand factor, a protein in the blood involved in hemostasis. It is designed to inhibit the interaction between vWF and platelets.

“The U.S. approval of Cablivi provides a much-needed treatment option for people facing this challenging disease. There have been limited medicines available to treat aTTP until now,” said Olivier Brandicourt, CEO of Sanofi. “Cablivi marks the first U.S. approval in our newly formed rare blood disorders franchise, and we look forward to continuing to provide important medicines for people living with these very serious diseases.”

Cablivi received FDA Fast Track designation and was evaluated under Priority Review, which is reserved for medicines that represent significant improvements in safety or efficacy in treating serious conditions.

The approval of Cablivi in the United States is based on the results of the pivotal multicenter, randomized, double-blind, placebo-controlled phase 3 clinical study known as HERCULES. This trial evaluated the efficacy of Cablivi in combination with plasma exchange and immunosuppressive therapy versus placebo, plasma exchange, and immunosuppressive therapy in 145 adults experiencing an episode of aTTP.

In the HERCULES study, treatment with Cablivi in combination with plasma exchange and immunosuppression resulted in a significantly shorter time to platelet count response versus plasma exchange and immunosuppression alone, the study’s primary efficacy endpoint.

In secondary endpoints, Cablivi showed a significant reduction on a composite endpoint of aTTP-related death, recurrence of aTTP, or a major thromboembolic event during study drug treatment versus plasma exchange and immunosuppression alone (12.7 percent vs. 49.3 percent); and a significantly lower percentage of aTTP recurrences in the overall study period versus plasma exchange and immunosuppression alone (13 percent vs. 38percent). Results of this study were published in the New England Journal of Medicine in January 2019.

In the HERCULES and TITAN (Phase 2) clinical trials, the most frequently reported adverse reactions were epistaxis (bleeding from the nose) 29%, headache 21% and gingival (gums) bleeding 16%. In the placebo group, two deaths were reported in the TITAN study and three deaths in the HERCULES study. No deaths were reported during the study drug treatment period in the Cablivi group in the TITAN and HERCULES studies. However, one death was reported in the HERCULES study during the treatment-free follow up period, which was determined not to be Cablivi treatment related.

February 7, 2019
Photo: Olivier Brandicourt, CEO of Sanofi