Interview with Prof. Iacopo Olivotto
di Francesca Conti
Professor Olivotto, how has the therapeutic approach to rare heart diseases evolved in recent years?
“I have been working on these diseases for 30 years and, until about 25 years ago, there were no significant new pharmacological advances. However, in the last 5 years we have seen a real change: many initiatives have emerged and the pharmaceutical industry has also started to take a serious interest in these diseases. This has led to the birth of start-ups engaged in the development of new molecules, some of which are aimed at extremely rare diseases, such as Danon disease. For the latter, gene therapy represents hope, even if it is still in an early stage. On the other hand, for less rare diseases, such as Hypertrophic Cardiomyopathy, we have more concrete and advanced approaches thanks to specific molecules.”
What are the most significant innovations in Hypertrophic Cardiomyopathy?
“An innovative drug has been developed for this pathology, the Mavacamten. It is a myosin inhibitor that acts directly on the heart's contractile apparatus, normalizing the excess contraction that is the basis of the disease. This drug is the first specific for hypertrophic cardiomyopathy and was approved by the American FDA in 2020 and by the European EMA in July 2023. In Italy, we have had the opportunity to participate in clinical studies and, subsequently, to offer the drug through an early access program (Early Access Program or “compassionate use”) guaranteed by the manufacturer. Unfortunately, this program has been interrupted while waiting for the reimbursement of the drug. While in much of Europe it is already available, in Italy we do not yet have a precise date, which is a cause for concern. We have many patients with significant symptoms who could greatly benefit from this treatment.”
How do international guidelines position themselves with respect to this drug?
“The 2023 European guidelines assign to the Mavacamten a class 2 indication, while the more recent American ones (2024) promote it to class 1, and this means a very strong indication. This reflects the international recognition of the importance of the drug. Furthermore, Mavacamten has received prestigious awards, such as the one for the innovative drug of the year in England. It represents a valid alternative to surgery, which does not guarantee optimal results if it is not performed by cardiac surgeons with great experience in its execution. This is an important turning point for a pathology that can have a significant impact on the quality of life.”
Do you think that the role of patient associations could be crucial in this context?
“We hope not, because it should not be necessary to involve a patient association to obtain access to a drug that has already been approved and recognized as innovative in Europe. I think the delay may depend on the process of negotiating the relatively high price, requested by the manufacturing company. Although Mavacamten is an expensive drug, the price requested is not comparable to that of some cancer treatments or drugs for other rare diseases, which can even exceed hundreds of thousands of euros per year. We hope that a compromise will be reached soon, because patients cannot afford to wait. This drug represents a concrete and immediate hope for many people.”
Prof. Iacopo Olivotto is the Chief of the Cardiology Unit at Meyer University Children's Hospital, Chief of the Cardiomyopathy Service at Careggi University Hospital, and Professor of Cardiovascular Medicine at the University of Florence, Italy. Over the past two decades, his primary clinical and research interests have included various aspects of cardiomyopathies, with a particular focus on the translational investigation of hypertrophic cardiomyopathy. Prof. Olivotto has pioneered the design and execution of randomized clinical trials in genetic cardiomyopathies, including Explorer HCM (as lead authors) and the Sequoia HCM trials involving cardiac myosin inhibitors for symptomatic obstructive hypertrophic cardiomyopathies. He has co-authored over 400 articles in international peer-reviewed journals. Prof. Olivotto is a co-founder of The Sarcomeric Human Cardiomyopathy Registry (Share), ICON (International Cardiomyopathy Network), and the Hypertrophic Cardiomyopathy Medical Association.