Adzynma Engineered ERT Therapy Approved for Prophylactic, On-Demand cTTP Treatment

The FDA has approved Takeda Pharmaceuticals’ Adzynma (TAK-755) as a prophylactic or on demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).¹

“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, Center for Biologics Evaluation and Research, FDA, said in a statement.¹ “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.”

cTTP is a rare and life-threatening blood clotting disorder caused by mutations in the ADAMTS13 gene, the encoded enzyme from which regulates blood clotting. The disease involved severe bleeding episodes, strokes and damage to vital organs and can be fatal when untreated. Current treatments for people with chronic disease include prophylactic plasma-based therapy to replenish the absent or low ADAMTS13 enzyme.

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Adzynma is an intravenous infusion of genetically engineered ADAMTS13 enzyme that may be administered once every other week as prophylactic ERT to help reduce the risk of disease symptoms or as an on-demand ERT for treatment of an acute event.

The most recent data on Adzynma were from a phase 3 trial (NCT04683003) presented in June 2023 from 46 patients who were randomized to receive 6 months of treatment with either Adzynma or plasma-based therapies and then crossed over to the other treatment for 6 months. No patient had an acute TTP event while receiving prophylactic treatment and the incidence of thrombocytopenia, the most frequently observed TTP manifestation, was reduced by 60%, as compared to plasma-based therapy (95% CI, 0.3-0.7). Investigators observed a favorable safety and tolerability profile, with 10.3%of treated patients ages 12-68 experiencing treatment-emergent adverse events (TEAEs) compared with to 50% of patients receiving plasma-based therapy.²

“These findings suggest that recombinant ADAMTS13 is a promising innovative investigational treatment for patients with cTTP,” Marie Scully, MD, Department of Hematology, University College London Hospitals, London, United Kingdom, said in a statement at that time.² “Given the high burden of illness these patients experience, complicated by unpredictable acute episodes and multiple disease-related complications, this is a much-needed option, supported through a first-of-its-kind clinical trial.”

REFERENCES
1. FDA approves first treatment for patients with rare inherited blood clotting disorder. News release. FDA. November 9, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-rare-inherited-blood-clotting-disorder
2. Pivotal phase 3 data presented at ISTH 2023 Congress spotlight TAK-755 prophylaxis for patients with congenital thrombotic thrombocytopenic purpura (cTTP). News release. Takeda Pharmaceuticals. June 25, 2023. https://www.businesswire.com/news/home/20230622882569/en/Pivotal-Phase-3-Data-Presented-at-ISTH-2023-Congress-Spotlight-TAK-755-Prophylaxis-for-Patients-with-Congenital-Thrombotic-Thrombocytopenic-Purpura-cTTP