Clinicians succeed in first test of drug for severe blood clotting disorder

A breakthrough in the treatment of immune thrombotic thrombocytopenic purpura (iTTP) has been achieved by a team from Massachusetts General Hospital, part of the Mass General Brigham healthcare system. The team successfully utilized a new drug to save the life of a patient suffering from this rare condition, marked by unchecked clotting in small blood vessels. This landmark case, which represents the first clinical application of the drug for iTTP, has been detailed in the New England Journal of Medicine.

The leading investigator, Dr. Pavan K. Bendapudi, an expert in the Division of Hematology and Blood Transfusion Service at Massachusetts General Hospital and an assistant professor at Harvard Medical School, explained the significance of the drug. The drug is a recombinant form of the enzyme ADAMTS13, which is deficient in patients with iTTP. In this particular case, it successfully reversed the patient's severe condition.

iTTP is triggered by an autoimmune response against ADAMTS13, an enzyme essential for breaking down a large blood-clotting protein. Traditional treatment involves plasma exchange, a process that eliminates harmful antibodies and supplements ADAMTS13. While plasma exchange can induce a clinical response in most patients, it only restores about half of the normal ADAMTS13 levels. The recombinant form of human ADAMTS13 (rADAMTS13), however, promises a more substantial increase in enzyme levels.

Originally, rADAMTS13 was approved for congenital thrombotic thrombocytopenic purpura, a genetic condition characterized by a complete lack of the ADAMTS13 gene. The effectiveness of rADAMTS13 in iTTP was uncertain due to the presence of inhibitory antibodies against ADAMTS13. Nevertheless, Dr. Bendapudi and his team were granted permission by the US Food and Drug Administration to use rADAMTS13 on compassionate grounds for a patient with iTTP who was unresponsive to other treatments.

Remarkably, the administration of rADAMTS13 rapidly countered the disease in the patient, challenging the prevailing belief that anti-ADAMTS13 antibodies would nullify the drug's effectiveness in iTTP. "We were the first in the United States to use rADAMTS13 for treating iTTP, and it successfully saved a young mother's life," Dr. Bendapudi stated.

The infused rADAMTS13 managed to overpower the inhibitory antibodies in the patient, reversing the thrombotic impacts of iTTP almost immediately—an outcome that daily plasma exchange had failed to achieve. Dr. Bendapudi highlighted the potential of rADAMTS13 to transform the standard care for acute iTTP, although he stressed the need for larger, well-structured clinical trials to validate these findings.

In pursuit of this goal, a phase 2b randomized clinical trial of rADAMTS13 in iTTP has recently commenced. This trial aims to provide more comprehensive data on the drug's efficacy and safety, potentially leading to a new standard of treatment for patients suffering from this life-threatening condition.