EU Approves Sanofi's Cablivi as First Targeted Therapy for Rare Blood Clotting Disorder aTTP

Key Insights

• The European Commission has authorized Cablivi (caplacizumab) as the first specific treatment for acquired thrombotic thrombocytopenic purpura (aTTP), a rare and life-threatening blood clotting disorder.
• Clinical trials involving 220 adults demonstrated Cablivi significantly reduced platelet count normalization time and decreased aTTP-related complications when added to standard care, with no deaths reported in the treatment group.
• The approval marks a significant advancement in aTTP treatment, where current standard therapy still carries up to 20% mortality rate, with Cablivi also under priority review by the FDA.

The European Commission has granted approval for Sanofi's Cablivi (caplacizumab), marking a significant breakthrough as the first therapeutic specifically indicated for treating adults with acquired thrombotic thrombocytopenic purpura (aTTP), a rare and potentially fatal blood clotting disorder.

Disease Impact and Current Treatment Challenges

aTTP affects approximately one in 250,000 people and is characterized by extensive blood clot formation in small vessels throughout the body. The condition can lead to severe complications including thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and widespread organ damage, particularly affecting the brain and heart. Current standard treatment, consisting of daily plasma exchange (PEX) and immunosuppression, is associated with a mortality rate of up to 20%, with most deaths occurring within the first month of diagnosis.

Clinical Trial Results Demonstrate Significant Benefits

The approval is supported by robust clinical evidence from the phase II TITAN and phase III HERCULES studies, which evaluated the drug in 220 adult patients. The HERCULES trial showed that Cablivi, when added to standard care, achieved several crucial outcomes:

• Significant reduction in time to platelet count response
• Decreased incidence of aTTP-related death and recurrence
• Reduced risk of major thromboembolic events during treatment
• Notable reduction in plasma exchange requirements
• Shorter stays in intensive care units and hospitals

Importantly, while no deaths were reported in the Cablivi treatment groups across both studies, two fatalities occurred in the placebo group.

Expert Perspective on Treatment Impact

Professor Marie Scully of University College London Hospitals emphasized the significance of this approval: "aTTP is a devastating disease. Many patients undergoing current standard of care treatment continue to be at risk of developing acute thrombotic complications, including stroke and heart attack, recurrence of the disease, lack of treatment response and death."

She added that Cablivi's approval "provides an important addition to the standard of care treatment for patients with aTTP in Europe because it can significantly reduce time to platelet count normalisation and induce a clinically meaningful reduction in recurrences."

Innovation and Future Availability

As the first nanobody-based medicine from Sanofi's pipeline to receive regulatory approval, Cablivi will be integrated into Sanofi Genzyme's Rare Blood Disorders franchise. The company is now working with relevant authorities to ensure availability across Europe.

The drug's potential impact may soon extend beyond Europe, as the U.S. Food and Drug Administration (FDA) has accepted a priority review for caplacizumab in treating adult aTTP patients, with a decision expected in February of the following year.