Caplacizumab-yhdp (Cablivi): the first therapy for the treatment of aTTP

Last Updated on

February 07, 2019 – The American Food and Drug Administration (FDA) just approved Caplacizumab-yhdp (Cablivi), the first therapy specifically indicated, in combination with plasma exchange and immunosuppressive therapy, for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), a rare and life-threatening disorder that causes blood clotting.

aTTP is a blood disorder that results in blood clots forming in small blood vessels throughout the body. This results in a low platelet count, low red blood cell count due to their breakdown, and often kidneys, heart, and brain dysfunction. Symptoms may include large bruises, fever, weakness, shortness of breath, confusion, and headacheRepeated episodes may occur.

In about half of cases a trigger is identified, while in the remainder the cause remains unknown. Known triggers include bacterial infections, certain medications, autoimmune diseases such as lupus, and pregnancy. Moreover, patients can develop aTTP because of conditions such as cancer, HIV, or after having surgery, bone marrow transplantation or chemotherapy. The underlying mechanism typically involves antibodies inhibiting the enzyme ADAMTS13, the von Willebrand factor-cleaving protease (VWFCP ). This results in decreased break down of large multimers of von Willebrand factor (vWF) into smaller units. Less commonly TTP is inherited from a person’s parents, known as Upshaw–Schulman syndrome, such that ADAMTS13 dysfunction is present from birth. Diagnosis is typically based on symptoms and blood tests. It may be supported by measuring activity of or antibodies against ADAMTS13. About 1 per 100,000 people are affected. Onset is typically in adulthood and women are more often affected.

With plasma exchange the risk of death has decreased from more than 90% to less than 20%. However, plasma exchange is an ordeal in its own right. Patients with aTTP endure hours of treatment with daily plasma exchange, which requires being attached to a machine that takes blood out of the body and mixes it with donated plasma and then returns it to the body. Even after days or weeks of this treatment, as well as taking drugs that suppress the immune system, such as glucocorticoids and rituximab, many patients will have a recurrence of aTTP.

Caplacizumab-yhdp (Cablivi) is the first targeted treatment that inhibits the formation of blood clots. It provides a new treatment option for patients that may reduce recurrences. Caplacizumab-yhdp (Cablivi) is a bivalent VHH designed an an anti-von Willebrand factor humanized immunoglobulin. It acts by blocking platelet aggregation to reduce organ injury due to ischemia.

The efficacy of Caplacizumab-yhdp (Cablivi) was studied in a clinical trial of 145 patients who were randomized to receive either Caplacizumab-yhdp (Cablivi) or a placebo. Patients in both groups received the current standard of care of plasma exchange and immunosuppressive therapy. The results of the trial demonstrated that platelet counts improved faster among patients treated with Caplacizumab-yhdp (Cablivi), compared to placebo. Treatment with Caplacizumab-yhdp (Cablivi) also resulted in a lower total number of patients with either aTTP-related death and recurrence of aTTP during the treatment period, or at least one treatment-emergent major thrombotic event (where blood clots form inside a blood vessel and may then break free to travel throughout the body).The proportion of patients with a recurrence of aTTP in the overall study period (the drug treatment period plus a 28-day follow-up period after discontinuation of drug treatment) was lower in the Caplacizumab-yhdp (Cablivi) group (13 percent) compared to the placebo group (38 percent), a finding that was statistically significant.

Common side effects of Caplacizumab-yhdp (Cablivi) reported by patients in clinical trials were bleeding of the nose or gums and headache. The prescribing information for Caplacizumab-yhdp (Cablivi) includes a warning to advise health care providers and patients about the risk of severe bleeding. Health care providers are advised to monitor patients closely for bleeding when administering Caplacizumab-yhdp (Cablivi) to patients who currently take anticoagulants.

See this patients journey:

Print Friendly, PDF & Email

 

Tags: , , , , , , , ,
About the Author
Joseph Gut - thasso Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

Your opinion

Comment

@peepso_user_1(thassodotcom) This is difficult to endure.
@peepso_user_3(20urbain05) Great post.
1 year ago 1 year ago

thasso: conditions

thasso: newest tweets

thasso: recent comments

View my Flipboard Magazine.

thasso: categories

thasso: archives

thasso: simple chat

You must be a registered user to participate in this chat.

  • Metabolomics meets genomics to improve patient diagnosis July 7, 2020
    A patient and family walk into a doctor's office. They hope that the latest tests will reveal what is causing the patient's illness and end the diagnostic odyssey they have been going through for years. Having an accurate diagnosis also means that maybe there is a treatment that at least can alleviate the patient's condition.
  • Researchers develop new approach to study the genetics of human disease July 7, 2020
    Many heritable immune diseases such as rheumatoid arthritis and blood-cell related traits derive from critical proteins not being made or not functioning correctly. But exactly how a person's genes, the regulation of these genes and how the resulting proteins interact to cause disease is not widely understood.
  • Common inherited genetic variant identified as frequent cause of deafness in adults July 6, 2020
    A common inherited genetic variant is a frequent cause of deafness in adults, meaning that many thousands of people are potentially at risk, reveals research published online in the Journal of Medical Genetics.
  • Rsearchers create an analytic tool that opens a new frontier of cancer discovery July 6, 2020
    Gene coding regions constitute 2% of the human genome. St. Jude Children's Research Hospital scientists have developed a computational tool to identify alterations that drive tumor formation in the remaining 98% of the genome. The method will aid discovery of oncogenes and advances in precision medicine for children and adults with cancer.
  • Discovery of new disease-susceptibility gene for steroid-sensitive nephrotic syndrome July 3, 2020
    An international research collaboration, including Professor Iijima Kazumoto et al. (of the Department of Pediatrics, Kobe University Graduate School of Medicine) has revealed that NPHS1 is a disease-susceptibility gene for steroid-sensitive nephrotic syndrome in children. The NPHS1 gene encodes nephrin, a component protein for the renal glomerulus slit diaphragm, which prevents protein from being passed […]
  • Hearing and visual impairments linked to elevated dementia risk July 8, 2020
    Older adults with both hearing and visual impairments--or dual sensory impairment--had a significantly higher risk for dementia in a recent study published in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring.
  • Certain jobs linked to higher risk of knee osteoarthritis July 8, 2020
    Workers in jobs that typically involve heavy lifting, frequent climbing, prolonged kneeling, squatting, and standing face an increased risk of developing knee osteoarthritis. That's the conclusion of a new analysis published in Arthritis Care & Research.
  • Bacteria in infants' first stool may indicate their risk of obesity July 8, 2020
    Meconium--the earliest stool of an infant -- is composed of materials ingested during the time the infant spends in the uterus. A new study published in Pediatric Obesity found that the types of normal bacteria found in the meconium may predict an infant's likelihood of later developing obesity.
  • New trial results question standard treatment plan for rheumatoid arthritis July 8, 2020
    In a clinical trial of patients with rheumatoid arthritis, treatment with a drug called upadacitinib provided greater benefits than methotrexate, the most commonly used initial therapy for rheumatoid arthritis.
  • Early clinical trial tests treatment strategy for pancreatic cancer July 8, 2020
    Pancreatic cancer carries a poor prognosis, and it often goes undetected until advanced stages. A new BJS (British Journal of Surgery) study indicates that a certain cocktail of chemotherapy drugs may be a safe and effective treatment option for patients with a metastatic form of the disease.
Top