The European Commission has approved PiaSky® (crovalimab), a novel recycling monoclonal antibody, for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) in adults and adolescents aged 12 years or older weighing at least 40 kg. This approval marks a significant advancement in PNH treatment, offering patients the first monthly subcutaneous option with self-administration capabilities.
PNH is a rare and life-threatening blood disorder characterized by the destruction of red blood cells by the complement system, a component of the innate immune system. The condition causes symptoms including anaemia, fatigue, and blood clots, with potential progression to kidney disease.
Reducing Treatment Burden Through Innovation
The approval addresses a significant challenge faced by PNH patients who typically require frequent intravenous infusions and regular clinic visits for treatment. Professor Alexander Röth, Head of Classical Haematology and Haemostasis at the West German Cancer Centre, University Hospital Essen, emphasized the impact on patients' lives: "People with PNH are often burdened with life-long, frequent intravenous infusions with time-consuming clinic visits, meaning that their lives, as well as their caregivers' and families' lives, may revolve around the demands of their treatment."
PiaSky's monthly subcutaneous administration represents a marked improvement over current standard treatments like eculizumab, which requires intravenous infusions every two weeks. Following adequate training, patients can self-administer PiaSky, potentially reducing disruption to their daily lives.
Innovative Recycling Antibody Technology
Developed by Chugai Pharmaceutical and commercialized by Roche, PiaSky employs proprietary Recycling Antibody® technology that enables a single antibody molecule to bind with the C5 protein multiple times. This innovation allows the medication to remain effective longer in the body while requiring only a small volume of medicine.
"PiaSky advances complement inhibition through its innovative recycling technology, which enables monthly SC administration by allowing the medicine to bind and inhibit the C5 protein multiple times and to act longer in the body with a small volume of medicine," explained Dr. Osamu Okuda, Chugai's President and CEO.
The antibody also binds to C5 at a different site than existing treatments, potentially offering an option for patients with specific C5 gene mutations who don't respond to current therapies. This mutation appears in approximately 3.2% of Japanese PNH patients.
Clinical Evidence Supporting Approval
The European approval is based primarily on results from the Phase III COMMODORE 2 study, which evaluated PiaSky in patients who had not previously received C5 inhibitor treatment. The trial demonstrated that PiaSky administered subcutaneously every four weeks achieved disease control comparable to intravenous eculizumab given every two weeks.
Key findings showed PiaSky was non-inferior to eculizumab in controlling hemolysis (destruction of red blood cells) and avoiding the need for transfusions. The safety profile was similar between the two treatments, with adverse event rates of 78% for PiaSky and 80% for eculizumab.
The application included supportive data from two additional Phase III studies: COMMODORE 1, which evaluated patients switching from currently approved C5 inhibitors, and COMMODORE 3, conducted in China with patients new to C5 inhibitor treatment.
Global Regulatory Status and Future Applications
PiaSky has already received approval in multiple territories worldwide, including the United States, Japan, and China. The treatment is being investigated in a broad clinical development program that includes five Phase III studies and three earlier-phase studies for complement-mediated diseases beyond PNH, including atypical haemolytic uremic syndrome and sickle cell disease.
"The PiaSky approval brings a new option to the PNH treatment landscape, combining the disease control achievable through C5 inhibition with a cutting-edge recycling technology that enables monthly subcutaneous administration," said Levi Garraway, M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product Development.
Treatment Protocol
PiaSky treatment begins with an initial intravenous infusion followed by weekly subcutaneous loading doses during the first month. Patients then transition to monthly subcutaneous maintenance doses. After appropriate training, patients have the option to self-administer the medication, potentially reducing the need for frequent clinic visits.
This approval represents a significant advancement in PNH management, offering patients greater flexibility and potentially improving quality of life while maintaining effective disease control.
