FDA Approves First Treatment for Patients With Rare Congenital Blood Disorder

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On November 9, the U.S. Food and Drug Administration (FDA) approved ADAMTS13, recombinant-krhn (Adzynma), the first genetically engineered protein product indicated for prophylactic or on-demand enzyme replacement therapy in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP), a rare and life-threatening blood-clotting disorder.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” said Peter Marks, MD, PhD, Director of the FDA’s Center for Biologics Evaluation and Research. “Without treatment, cTTP is ultimately fatal. [This] approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

More About cTTP

The very rare, inherited blood-clotting disorder called cTTP is caused by a disease-causing mutation in the ADAMTS13 gene, which is responsible for making an enzyme, also named ADAMTS13, that regulates blood clotting. A deficiency in this enzyme causes blood clots to form in the small blood vessels throughout the body.

It is estimated that cTTP affects fewer than 1,000 people in the United States. Symptoms typically develop in infancy or early childhood, but in some cases, may develop in adulthood and may first manifest during pregnancy. Individuals with cTTP may experience severe bleeding episodes, strokes, and damage to vital organs. If left untreated, the disease can be fatal. Treatment for cTTP typically involves prophylactic plasma-based therapy for individuals with chronic disease to reduce the risk of clotting/bleeding by replenishing the absent/low ADAMTS13 enzyme.

Novel Therapy: Mechanism of Action and Efficacy

The newly approved drug is a purified recombinant form of the ADAMTS13 enzyme that works by providing a replacement for the low levels of the deficient enzyme in patients with cTTP. For prophylactic enzyme replacement therapy, recombinant ADAMTS13 is administered to help reduce the risk of disease symptoms. The product may also be administered as an on-demand enzyme replacement therapy for treatment when the patient is experiencing an acute event. It is administered intravenously once every other week for prophylactic enzyme replacement therapy, and once daily for on-demand enzyme replacement therapy. 

The safety and effectiveness of recombinant ADAMTS13 were demonstrated in a global study evaluating prophylactic and on-demand enzyme replacement therapy with the agent compared to plasma-based therapies in patients with cTTP. Its efficacy in the prophylactic treatment of patients with cTTP was evaluated in 46 patients who were randomly assigned to receive 6 months of treatment with either recombinant ADAMTS13 or plasma-based therapies (period 1), then crossed over to the other treatment for 6 months (period 2). The efficacy was demonstrated based on the incidence of thrombotic thrombocytopenic purpura (TTP) events and TTP manifestations, as well as the incidence of the need for supplemental doses. 

The efficacy of on-demand enzyme replacement therapy was evaluated based on the proportion of acute TTP events responding to recombinant ADAMTS13 in both the prophylactic and on-demand cohorts throughout the duration of the study. All acute and subacute TTP events resolved after treatment with either recombinant ADAMTS13 or plasma-based therapies. 

The most common side effects associated with recombinant ADAMTS13 include headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness, and vomiting. During the clinical studies, no adverse events, including allergic reactions, were observed during the administration of recombinant ADAMTS13.

The application was awarded a Rare Pediatric Disease Priority Review Voucher and granted Priority Review, Fast Track, and Orphan Drug designations.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.