FDA Approves First Therapy for Rare Blood-Clotting Disorder

February 18, 2019

On Wednesday, February 6th, FDA approved the Cablivi®(caplacizumab-yhdp) injection, the first product approved in combination with plasma exchange and immunosuppression specifically for adults with acquired thrombotic thrombocytopenic purpura (aTTP).

What is aTTP?

aTTP is the development of extensive blood clots in the small blood vessels throughout the body of a patient. These clots can cut off oxygen and blood supply to major organs and cause strokes and heart attacks that can lead to brain damage or death. The disorder can be developed in patients suffering from certain conditions such as cancer, HIV, pregnancy, lupus or infections, or after having surgery, a bone barrow transplant, or chemotherapy. An estimated 20% of patients die from aTTP episodes, with most deaths occurring within 30 days of diagnosis. In the United States it is reported that aTTP affects fewer than 2,000 adults each year.

In a recent statement, Dr. Richard Pazdur, 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 stated that “patients with aTTP endure hours of treatment involving 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.” In this release, Dr. Pazdur also points out that “even after days or weeks of this treatment, as well as taking drugs that suppress the immune system, many patients will have a recurrence of aTTP.”

Cablivi Clinical Trial

The Cablivi injection was evaluated in the pivotal multi-center, randomized, double-blind, placebo-controlled Phase 3 clinical trial known as HERCULES. The trial involved 145 patients who randomly received either Cablivi or a placebo, and all patients received the current standard care of plasma exchange and immunosuppressive therapy. The overall study period included the drug treatment period plus a 28-day follow up period after discontinuation of the treatment.

The results of the clinical trials displayed:

  • Patients’ platelet counts improved faster when treated with Cablivi compared to the placebo
  • A lower total number of patients experiencing aTTP-related death and recurrence of aTTP during the treatment period, “or at least one treatment-emergent major thrombotic event, where blood clots form inside a blood vessel and may then break free to travel throughout the body,” was reported with treatment with Cablivi
  • Recurrence of aTTP during the overall study period was lower in the Cablivi group (13%) than the placebo group (38%), which proved to be statistically significant

Common side effects that were reported by patients during the trials were nose bleeds (29%) or gingival (gums) bleeding (16%) and headache (21%). When administering Cablivi, health care providers are advised to monitor for bleeding in patients who currently take anticoagulants.

Cablivi Approval

FDA granted Priority Review and Orphan Drug Designation to Ablynx for Cablivi, which provides incentives to assist and encourage the development of drugs for rare diseases.  Cablivi is expected to be available in the United States late in the first quarter of 2019.

Are you in the process of developing an Orphan drug or other FDA-regulated product? We can help determine if your product is eligible for priority review, Orphan Drug Designation, or any of FDA’s other expedited approval programs.  To learn more about our services and how we can help you achieve successful interactions with the FDA, contact us today.



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