FDA Approves Takeda’s Treatment for Rare Blood Clotting Disorder

The FDA has approved Takeda’s Adzynma as the first genetically engineered protein medication for the preventative treatment or for on-demand enzyme replacement therapy in patients with congenital thrombotic thrombocytopenic purpura (cTTP).¹

The FDA granted the application for Adzynma with a Rare Pediatric Disease Priority Review Voucher, as well as Priority Review, Fast Track, and Orphan designations. cTTP affects fewer than 1,000 individuals in the United States.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,” said FDA Director of the Center for Biologics Evaluation and Research Peter Marks, MD, PhD, in a press release.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.”

In patients with cTTP, a rare and life-threatening blood disorder, blood clots form in small blood vessels throughout the body, with symptoms typically manifesting during infancy or early childhood; however, some cases do not develop until patients are adults.² The symptoms of cTTP, which may include fatigue, paleness, jaundice, shortness of breath, and a rapid heart rate, typically result from hemolytic anemia, low platelets, and neurologic dysfunction, according to the National Institutes of Health.²

Abnormal clotting can cause nervous system issues that include personality changes, headaches, confusion, and seizures, as well as abnormal renal function, cardiovascular and gastrointestinal issues. In addition to developing during infancy or early childhood, cTTP can develop during adulthood and during pregnancy. The disease is caused by alterations in the ADAMTS13 gene, which produces an enzyme that regulates blood clotting.²

A deficiency in that enzyme, also called ADAMTS13, leads to blood clots that develop in small blood vessels throughout the body. If cTTP goes untreated, it can lead to death.

Patients with cTTP may suffer from severe bleeding episodes, strokes, and may experience damage to vital organs. cTTP is normally treated by prophylactic plasma-based therapy for patients who have chronic disease to lower the risk of clotting and bleeding by replenishing either absent or low levels of the ADAMTS13 enzyme.

Adzynma, a purified recombinant form of the ADAMTS13 enzyme, acts as a replacement for low enzyme levels in patients with cTTP. Adyznma can also be administered as an on-demand enzyme replacement therapy when patients experience an acute event. The medication is administered intravenously once every other week for prophylactic enzyme replacement therapy or once daily for on-demand enzyme replacement therapy.¹

Adzynma demonstrated both safety and efficacy in a global study that analyzed its use both as a prophylactic and for on-demand enzyme replacement therapy as compared with other plasma-based treatments for cTTP.¹

The study included 46 patients who were randomly assigned to receive six months of treatment with Adzynma or plasma-based treatments before crossing over to the other treatment for six months. Efficacy was established based on the incidence of TTP events and manifestations, and based on the need for supplemental doses of the drug.¹

Adzynma’s effectiveness as on-demand enzyme replacement therapy was analyzed based on the proportion of acute TTP events that responded to the drug in the both the prophylactic and the on-demand patient cohorts during the study. Acute and subacute TTP events were shown to resolve following administration of Adzynma or plasma-based treatments.¹

In terms of safety, the most common adverse events (AEs) associated with Adzynma included headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness, and vomiting. There were no observed AEs, such as allergic reactions, observed during the administration of Adzynma during clinical trials.¹

References

1. FDA Approves First Treatment for Patients with Rare Inherited Blood Clotting Disorder. FDA. News release. November 9, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-rare-inherited-blood-clotting-disorder

2. Congenital thrombotic thrombocytopenic purpura. Genetic and Rare Disease Information Center. Webpage. Accessed November 9, 2023. https://rarediseases.info.nih.gov/diseases/9430/congenital-thrombotic-thrombocytopenic-purpura