First Medicine for a Rare Blood Clotting Disorder Receives FDA Approval
In this article
On 9 November 2023, the FDA (US Food and Drug Administration) approved Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children with congenital thrombotic thrombocytopenic purpura (TTP), a rare, life-threatening blood clotting disorder.
Adzynma is the first recombinant protein medicine used for preventive and on-demand enzyme replacement in people with this blood clotting disorder.
Congenital thrombotic thrombocytopenic purpura (TTP) is a rare inherited disease caused by a mutation in the gene producing ADAMTS13, an enzyme controlling blood clotting.
Its incidence is 1-2 per 100,000 births.
People with this genetic disorder often receive preventive plasma-based treatment supplying ADAMTS13 to reduce clotting and bleeding risks. Untreated disease can be fatal.
Congenital TTP usually appears within the first few months after birth, although it may emerge later. Symptoms include:
- Petechiae (small red spots on the skin)
- Purpura (purplish skin patches)
- Bleeding, for example from the nose, gums, gastrointestinal or urinary tract
- Headache
- Fatigue
- Weakness
- Loss of consciousness
- Seizures
- Heart attack
- Stroke
Treatment replaces the ADAMTS13 enzyme through plasma exchange or cryoprecipitate. Plasma exchange removes the liquid part of a patient’s blood and replaces it with healthy plasma. Cryoprecipitate is a plasma fraction containing high concentrations of ADAMTS13.
Inherited diseases pass from parents to children and result from mutations in parental genes.
Congenital TTP results from ADAMTS13 gene mutations disrupting production or function of the ADAMTS13 enzyme.
It is autosomal recessive, meaning children who inherit a mutated gene from each parent develop the disease.
If one parent carries a mutated gene, the child’s disease risk is 25%.
Its inherited nature can complicate treatment because people at risk need to be identified in advance and treatment started.
The First Biological Product for TTP Treatment
Adzynma is a purified recombinant form of ADAMTS13 designed to restore normal enzyme levels in congenital TTP. The FDA approval provides for preventive use against disease symptoms and on-demand use during an acute health problem.
Approval was based on a global phase 3 study in 46 patients comparing Adzynma with plasma-based therapy. For six months, patients were randomly assigned intravenous Adzynma or plasma-based therapy as preventive enzyme replacement every two weeks, or daily in an acute episode. They then crossed over to the other treatment for a further six months.
Early results showed that
- Adzynma reduced the most common congenital TTP symptom, thrombocytopenia, by 60% compared with plasma-based therapy.
According to Takeda, no patients receiving preventive Adzynma experienced an acute TTP episode during treatment.
Many plasma-treated patients experienced more adverse events than those receiving Adzynma. The most common Adzynma-associated effects were headache (31.3%), diarrhoea (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 recorded during treatment.
*
Image caption: The illustration was created by ChatGPT 4.0 using this prompt: “An abstract work featuring platelets and other blood cells and a landscape”
Sources
Was this article helpful?
Your feedback helps us improve our content.
Reader comments
Share your comment
Your name and comment are published only after administrator approval. Your email address is never shown to visitors.
Be the first to comment.