FDA Approves the First Drug Specifically Indicated for aTTP

On February 6, the FDA approved caplacizumab-yhdp (Cablivi), the first therapy specifically indicated for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP) in adults. The drug is approved for use in combination with plasma exchange and immunosuppressive therapy.

Patients with aTTP, a rare, life-threatening autoimmune blood disorder, experience blood clots in small blood vessels throughout the body. These clots can block vessels and decrease or stop blood flow to organs, causing neurological problems, fever, abnormal kidney function, abdominal pain, and heart problems.

Episodes of aTTP typically occur suddenly and last for days or weeks, and up to 20% of patients die from aTTP epidoses, with most deaths occurring within 30 days of diagnosis.

While aTTP is typically treated with plasma exchange and immune suppressants, relapses occur in up to 60% of patients who have aTTP. Caplacizumab, which is administered at the start of plasma exchange, targets von Willebrand factor (vWF), a protein in the blood that is involved in hemostasis. The drug, which is one of a novel class of therapeutic proteins based on single-domain antibody fragments, is designed to inhibit the interaction between vWF and platelets.

"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 in the division of hematology at the Wexner Medical Center at the Ohio State University, in a statement. "Cablivi provides new hope for adults in the [United States] suffering with aTTP and provides a much-needed treatment option to help effectively manage aTTP episodes."

Approval of caplacizumab was based on results of the HERCULES phase 3 clinical study in 145 adult patients with aTTP that evaluated the drug in combination with plasma exchange and immunosuppressive therapy versus placebo in combination with plasma exchange and immunosuppressive therapy.

In the study, patients who received the drug had a significantly shorter time to platelet count response versus the placebo group. Caplacizumab also showed a significant reduction on a composite end point of aTTP-related death, recurrence of aTTP, or a major thromboembolic event during the study versus plasma exchange and immunosuppression alone.

During the HERCULES study and the phase 2 TITAN study, the most frequently reported adverse events were bleeding from the nose, headache, and bleeding from the gums.

Sanofi, the maker of the drug, says that it expects the drug to launch in the late first quarter of 2019. The list price for the treatment of a single episode of aTTP will be $270,000, and Sanofi says that it will soon launch a patient support program and will provide eligible patients with financial assistance.