First Treatment Approved for Genetic Clotting Disorder

The FDA approved a recombinant ADAMTS13 protein product (Adzynma) as a prophylactic or on-demand enzyme replacement therapy for patients with congenital thrombotic thrombocytopenic purpura (cTTP).

The extremely rare, chronic blood clotting disorder is caused by a mutation in the ADAMTS13 gene that leads to deficiency in the ADAMTS13 enzyme, which causes blood clots to form in the small blood vessels throughout the body. Patients may experience severe bleeding episodes, strokes, and damage to vital organs.

According to the agency, cTTP affects fewer than 1,000 people in the U.S.

“Without treatment, cTTP is ultimately fatal,” Peter Marks, MD, PhD, director of FDA’s Center for Biologics Evaluation and Research, said in a statement. “Today’s approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

Approval of the ADAMTS13 product was based on results from a randomized open-label crossover phase III trial, as well as data from the continuation trial, that demonstrated reductions in acute and subacute TTP events compared with plasma-based therapy.

“Adzynma provides patients with a treatment option that replaces their deficient ADAMTS13 enzyme and offers a favorable efficacy and safety profile and reduced administration time and volume compared to current plasma-based therapies,” investigator Spero Cataland, MD, of the Wexner Medical Center at Ohio State University in Columbus, said in a press release from drugmaker Takeda.

In the phase III study, patients received 40 IU/kg of the recombinant ADAMTS13 product intravenously or plasma-based therapy every other week or weekly based on their regimen at enrollment for months 1 to 6 (period 1), crossing over to the alternate therapy for months 7 to 12 (period 2), with all patients receiving the protein product for months 13 to 18 (period 3).

No acute TTP events occurred among the 37 patients who received the recombinant therapy as prophylaxis, while there was one among the 38 patients receiving plasma-based therapy. And no subacute TTP events were reported in patients receiving the recombinant form of ADAMTS13 during periods 1 and 2, compared with five subacute TTP events in four patients receiving plasma-based therapies.

In the continuation period (period 3), two patients receiving the protein product as prophylaxis had two subacute events.

The mean annualized event rate of thrombocytopenia manifestations was 2.0 for patients receiving the recombinant therapy compared with 4.44 with the plasma-based therapies. Nine of 37 patients versus 19 of 38, respectively, experienced a manifestation.

The most common adverse events (5% or more) associated with the recombinant ADAMTS13 product were 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 the recombinant protein product.

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