FDA Approves Cablivi for Rare Blood Clotting Disorder

The US Food and Drug Administration (FDA) has approved Cablivi (caplacizumab-yhdp) injection, which is indicated for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange and immunosuppressive therapy.

Cablivi is the first approved therapy specifically indicated for aTTP, a rare and life-threatening disorder that causes patients to develop blood clots throughout the body.

"Patients with aTTP endure hours of treatment with daily plasma exchange, which requires being attached to a machine that takes blood out of the body and mixes it with donated plasma and then returns it to the body," said Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, in a press release.

Pazdur added that despite days or weeks of plasma exchange and immunosuppressive treatment, patients with aTTP can still experience a recurrence.

"aTTP is a very severe, life-threatening disease. For those faced with this rare diagnosis, the treatment and care can be difficult and the threat of recurrence is ever-present," said Spero R. Cataland, MD, Professor of Internal Medicine, Division of Hematology, Wexner Medical Center at the Ohio State University, in a statement.

The approval decision was supported by data from a phase 3 study of caplacizumab. The study—HERCULES—randomized 145 participants with aTTP to receive either caplacizumab or placebo. Participants received an initial intravenous dose followed by daily subcutaneous injections for up to 6 months. All patients also received standard of care plasma exchange and immunosuppressive therapy.

Patients treated with Cablivi experienced a significantly shorter time to platelet count response compared to the placebo group (Hazard Ratio 1.55 [95% confidence interval 1.10 - 2.20] P = .01), meeting the primary endpoint.

The active treatment group also had significant reduction of events in a composite endpoint of aTTP-related death, recurrence of aTTP, or a major thromboembolic event during study drug treatment compared to the placebo treatment group (12.7% vs. 49.3%; P <.0001).

The most commonly reported adverse effects of Cablivi during HERCULES and a previous phase 2 clinical trial were epistaxis 29%, headache 21%, and gingival bleeding 16%.

"Cablivi provides new hope for adults in the US suffering with aTTP and provides a much-needed treatment option to help effectively manage aTTP episodes," added Cataland.

Cablivi had previously been granted Priority Review and Orphan Drug designations. The FDA approval was granted to Ablynx, which was acquired by Sanofi in 2018.

Sanofi expects Cablivi to be available in the US late in the first quarter 2019 and states that the cost for treating a typical episode of aTTP with Cablivi will be $270,000.