FDA Approves Recombinant Enzyme to Treat Rare Blood Clotting Disorder

The U.S. Food and Drug Administration recently approved Adzynma, the first recombinant protein product indicated for prophylactic or on-demand enzyme replacement therapy (ERT) 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. Today’s approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

The FDA awarded Takeda Pharmaceuticals U.S.A. Inc. a Rare Pediatric Disease Priority Review Voucher and granted Adzynma Priority Review, Fast Track, and Orphan Drug designations.

What happens in congenital thrombotic thrombocytopenic purpura?

cTTP is a very rare, inherited blood clotting disorder caused by a mutation in the ADAMTS13 gene, which is responsible for making an eponymous enzyme 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, stroke, and damage to vital organs. If left untreated, the disease can be fatal. Treatment for individuals with chronic cTTP typically involves prophylactic plasma-based therapy to reduce the risk of clotting/bleeding by replenishing the absent/low ADAMTS13 enzyme.

Adzynma is a purified recombinant form of the ADAMTS13 enzyme. It compensates for the deficiencies caused by mutated ADAMTS13 in patients with cTTP. For prophylactic ERT, Adyznma is administered to help reduce the risk of disease symptoms. The product may also be administered as an on-demand ERT for treatment when the patient is experiencing an acute event. Adzynma is administered intravenously once every other week for prophylactic ERT, and once daily for on-demand ERT.

Safety and effectiveness of Adzynma 

The safety and effectiveness of Adzynma were demonstrated in a global study evaluating prophylactic and on-demand ERT with Adzynma compared to plasma-based therapies in patients with cTTP.

The efficacy of Adzynma in the prophylactic treatment of patients with cTTP was evaluated in 46 patients who were randomized to receive six months of treatment with either Adzynma or plasma-based therapies (Period 1), then crossed over to the other treatment for six months (Period 2). The efficacy was demonstrated based on the incidence of thrombotic thrombocytopenic purpura (TTP) events and TTP manifestations, as well as the need for supplemental doses. 

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

The most common side effects associated with Adzynma include headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness, and vomiting. During the clinical studies, no adverse events and/or allergic reactions were observed when Adzynma was administered.

- This press release was originally published on the U.S. Food and Drug Administration website