Transthyretin cardiac amyloidosis is a progressive disease in which a substance (amyloid protein) is deposited in the heart. This deposit causes the walls of the heart to be thicker and stiffer and patients suffer from fluid retention, fatigue and arrhythmias, which is why it is often called stiff heart syndrome. When it accumulates in the heart, it causes heart failure and ultimately death. It is known that it may have a genetic origin or be caused by age. Its prognosis is poor, and the median survival of patients without treatment is only 3 years.
But the results of a new study may radically change the scenario for this disease. The results of the first clinical trial with an amyloid-removing drug against transthyretin cardiac amyloidosis are very promising.
The study is the work of the team led by Dr. Pablo García-Pavía, Head of Familial Cardiopathies at the Puerta de Hierro University Hospital and researcher at the National Center for Cardiovascular Research (CNIC) and the Biomedical Network Research Center for Cardiovascular Diseases (CIBERCV), in Spain.
The study represents a great advance in a disease in which the treatments available to date, despite the fact that they prevent the accumulation of more amyloid protein and delay the progression of the disease, do not act against the amyloid that is already deposited in the heart.
Current treatment options include transthyretin stabilizing therapy and support to control cardiovascular complications, while heart transplantation is currently the only therapy capable of restoring heart function in this disease. Tafamidis, an oral transthyretin stabilizer recently marketed in Spain, is the only available drug targeted specifically for this disease and has been shown to improve survival and reduce the number of hospitalizations; however, it does not produce improvement in the disease.
The initial results of the study, in which 40 patients from France, the Netherlands, Germany and Spain have participated and which has been coordinated by Dr. García-Pavía at the Puerta de Hierro Hospital, show that the drug is safe and seems to reduce the amount of amyloid deposited in the heart.
Dr. Pablo Garcia-Pavia. (Photo: CNIC)
Developed by the Swiss company Neurimmune, the drug is an antibody with the ability to bind to the amyloid substance identified from the analysis of type B memory cells from healthy very old people.
In the study, the antibody was used to stimulate the defensive system of the patients and, thus, achieve the elimination of cardiac amyloid.
In the trial, the antibody was administered intravenously at progressively higher doses on a monthly basis for 12 months.
“Patients who received more doses of the drug apparently had a greater reduction in amyloid deposits in the heart and greater improvement in various cardiac parameters,” says Dr. García-Pavía.
In conclusion, this phase I proof-of-concept study demonstrates the safety profile of this drug in these patients and supports further clinical research with this compound to eventually reach patients.
Dr. García-Pavía is one of the world’s leading experts on this disease and is the leader of the document on the diagnosis and treatment of cardiac amyloidosis of the European Society of Cardiology, the recommendations that are followed internationally for the diagnosis and treatment of this disease.
His group at the Hospital Puerta de Hierro is one of the most prestigious internationally in this pathology and demonstrated years ago that this disease, which was previously considered very rare, is one of the most frequent causes of heart failure in people over the age of 65 years.
The study is titled “Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid.” And it has been published in the academic journal The New England Journal of Medicine (NEJM). Dr. García-Pavía has also recently presented the results of the clinical trial at the Heart Failure Congress of the European Society of Cardiology held in Prague (Czech Republic). (Source: CNIC)