Oncology: in Italia the drug against the genetic disease that induces ten tumours

Managing one patient with von Hippel-Lindau disease (VHL) is like managing 10 at the same time, as there are so many possibilities for the same person to develop tumours, both benign and malignant, in different organs of the body. It is a rare, complex and almost unknown condition. The average age of diagnosis is 26 years and it affects about 1,100 people in Italia.

In the absence of systemic therapy, the management of patients to date has been based on two cornerstones: surveillance and repeated surgery to remove the different tumours. In the course of their lives, approximately 70% of patients with VHL develop clear cell renal cell carcinomas, 60-80% central nervous system haemangioblastomas and approximately 5-10% pancreatic neuroendocrine tumours with consequent disabilities such as reduced or lost vision, motor or neurological impairment and renal failure.

100 years after the first article that described this disease, the Italian Medicines Agency has given the green light for the reimbursability of belzutifan, the first systemic drug for von Hippel-Lindau syndrome. "For patients, we have gone from hope to a concrete therapeutic opportunity that can change the history of the disease: I see every day that it works," emphasises Alfonso Massimiliano Ferrara, an endocrinologist at the Hereditary Tumours Unit of the Irccs Istituto Oncologico Veneto in Padua, who points to an emblematic datum: before the drug's introduction in 2018, studies showed that 92% of patients underwent surgery, after only 3%.

The research goes back a long way: in 1993 the VHL gene was identified, in 2013 the first experimental inhibitors were developed and in 2019 the three researchers William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza for their discoveries on hypoxia also closely linked to the VHL gene. 'The important and exciting thing for those who manage this disease,' Ferrara continues, 'is that patients are now able to use a word that used to hurt to talk about: future.

With the go-ahead from Aifa and the publication of reimbursability in the Official Gazette, the manufacturer of belzutifan, the US multinational Msd, will have to stop supplying the drug for compassionate use. "Our hope," emphasises Nicoletta Luppi, president and CEO of Msd Italia, "is that the regions will make the drug available to patients as soon as possible, also so as not to interrupt ongoing therapies. At the moment, six regions have already authorised the drug and identified the reference centre, but the waiting lists are still close to 100 days. Too long for a drug approved in 2021 by the US Food and drug administration, in 2025 by the European Medicines Agency, and today by Aifa.