Today, Takeda announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval, under exceptional circumstances, of recombinant ADAMTS13 (rADAMTS13) for treating ADAMTS13 deficiency in both children and adult patients suffering from congenital thrombotic thrombocytopenic purpura (cTTP). The European Commission (EC) will take the CHMP’s positive opinion into account when considering the potential marketing authorization for rADAMTS13 across the EU. If greenlit, rADAMTS13 will mark the first and sole enzyme replacement therapy available in the EU for addressing cTTP.
Obi Umeh, M.D., M.Sc., Vice President, Franchise Global Program Leader at Takeda, emphasized the critical impact of this advancement: “People living with cTTP experience serious, potentially fatal health challenges and have limited treatment options in the European Union. With this positive opinion for recombinant ADAMTS13, we are one step closer to offering patients in the EU the first treatment specifically indicated for cTTP. We look forward to the European Commission’s decision as we aspire to transform the standard of care for cTTP for more patients around the world.”
cTTP, an ultra-rare, chronic blood clotting disorder, stems from a deficiency in the ADAMTS13 enzyme. It is associated with acute events and debilitating chronic symptoms, including thrombocytopenia, microangiopathic hemolytic anemia, renal manifestations, stroke, and abdominal pain. If left untreated, acute TTP events have a mortality rate exceeding 90%.
The CHMP’s positive opinion was based on comprehensive evidence, including interim analysis of efficacy, pharmacokinetic, safety, and tolerability data from the initial randomized, controlled open-label, crossover Phase 3 trial in cTTP. The results of this trial (NCT03393975) were published in The New England Journal of Medicine in May 2024. Additionally, rADAMTS13 is undergoing investigation in adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP), the acquired form of TTP, in an ongoing Phase 2b trial (NCT05714969).
Recombinant ADAMTS13 (rADAMTS13) stands as the premier and sole recombinant “A disintegrin and metalloproteinase with thrombospondin motifs 13” (ADAMTS13) enzyme replacement therapy formulated for cTTP treatment. Marketed as ADZYNMA in the U.S. and Japan, rADAMTS13 secured approval from the U.S. Food and Drug Administration (FDA) and Japanese Ministry of Health, Labour, and Welfare (MHLW) for prophylactic and on-demand treatment of cTTP patients.
rADAMTS13 received Orphan Drug Designation (ODD) by the U.S. FDA for treating and preventing TTP, along with Fast Track and Rare Pediatric Disease Designation. Takeda also obtained a Rare Pediatric Disease Voucher from the U.S. FDA for rADAMTS13 approval. Previously, rADAMTS13 earned ODD from the European Medicines Agency (EMA) and Japanese MHLW for TTP treatment.
Congenital thrombotic thrombocytopenic purpura (cTTP) represents an ultra-rare, chronic, and debilitating clotting disorder linked to life-threatening acute events and chronic symptoms. TTP, estimated to have a prevalence of 2-6 diagnosed cases per million, encompasses both inherited and acquired forms. The inherited variant, cTTP, arises from ADAMTS13 deficiency, leading to the accumulation of ultra-large von Willebrand factor (VWF) multimers in the blood. This accumulation prompts uncontrolled platelet aggregation and adhesion, culminating in abnormal clotting in the body’s small blood vessels, associated with microangiopathic hemolytic anemia and thrombocytopenia.
cTTP presents acute and chronic manifestations, including stroke, renal, and cardiovascular complications. If untreated, acute TTP events carry a mortality rate exceeding 90%, and cTTP can inflict widespread organ damage and other comorbidities due to the ADAMTS13-deficient state.
