FDA approves first tx for rare, deadly clotting disorder

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“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,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

A version of this article first appeared on Medscape.com.