Rare diseases, Aifa ok for reimbursement of a new monoclonal antibody for atypical Seu

2023-05-16 15:50:19

The Italian Medicines Agency (AIFA) has approved the reimbursement of ravulizumab for the treatment of atypical haemolytic uremic syndrome (HUS). The therapy, a complement protein C5 inhibitor, can be prescribed to patients (adults or children) both naïve to complement inhibitors and already treated with eculizumab for at least 3 months and who have shown a response to the treatment. Alexion, AstraZeneca Rare Disease, announced it today during a press conference in Milan.

The new monoclonal antibody works by inhibiting the activity of the C5 protein in the terminal complement cascade, a part of the immune system. When activated in an uncontrolled way, the complement cascade overreacts, causing the body to attack its own healthy cells. Ravulizumab, the first and only long-acting C5 complement inhibitor, offering immediate, complete and sustained complement inhibition, increases the frequency of treatment administration from every 2 weeks to every 2 months, improving the quality of life of all patients affected by the disease.

Atypical HUS is a rare disease that affects more than 600 patients in Italy, both adults and children. It is characterized by chronic and uncontrolled activation of the complement system, which can cause progressive damage to vital organs, mainly the kidneys, through damage to blood vessel walls and blood clots. “This anomaly – underlines Gaetano La Manna, full professor of Nephrology at the University of Bologna and director of the Operational Unit of Nephrology, dialysis and transplantation at the Sant’Orsola Polyclinic in Bologna – leads to a state of chronic inflammation that causes damage to the blood vessel walls. This leads to an accumulation of platelets and leukocytes which greatly increases the risk of thrombus formation. The first organ to be damaged is usually the kidney, but damage can extend to the heart, lungs, brain and gastrointestinal system” . About 50% of patients with the syndrome require dialysis, suffer permanent kidney damage, or die within the first year.

Although atypical HUS is a pathology on a genetic basis for 50-70% of cases (the genes involved are Chf, Chf3r, Mcp, Cfi, Cfb And Cr) – the note continues – an event is often necessary to unleash evident symptoms , technically called a ‘trigger’, such as pregnancy, malignant hypertension, an organ transplant, kidney disease, an autoimmune disease, cancer, an infection or the abuse of certain drugs. In the past, plasma exchange or infusion was used to manage the disease, but this strategy has never really proved effective.

The new monoclonal antibody approved by Aifa has been tested in two multi-centre phase 3 clinical trials. The first, single-arm, involved naïve adult patients. The second, conducted on pediatric patients, was developed in a double arm involving both naïve patients and patients already treated with complement inhibitors. The new therapy demonstrated immediate, complete and sustained inhibition of C5 in all patients. In particular, the efficacy of ravulizumab was evaluated in terms of response to the treatment of thrombotic microangiopathy which represents the most evident clinical manifestation of the disease. “In adults treated with ravulizumab – reports Giuseppe Castellano, director of Complex Structure, associate professor of Nephrology at the University of Milan – 53% had a complete response to thrombotic microangiopathy in the initial evaluation period, equal to 26 weeks, and 61% in the first 12 months. Ravulizumab in the pediatric population achieved 94.4% complete response rate and 100% discontinued dialysis.”

“The benefits of lengthening the time between one infusion and another are important – remarked Paolo Chiandotto, president of the patient association Alice Project Association for the fight against Seu – First of all it means going to the hospital less times. In employed adults it means lose fewer hours of work, and the same thing goes for the parents of children affected by the disease.For children, who fortunately are a small percentage, this means missing fewer days of school.Overall, these advantages translate into greater general well-being since one feels less ‘connected’ to the hospital”. Anna Chiara Rossi, VP & General Manager Italy at Alexion, AstraZeneca Rare Disease, declares: “Since our inception, our research goal has been to develop innovative therapies capable of significantly improving the quality of life of people with rare diseases and their families. All this was possible thanks to the collaboration and continuous exchange of experiences with patients and clinicians. Being able to create an antibody capable of further improving both treatment and people’s daily lives is a source of great pride for us”.