Sanofi has FDA approval for its acquired thrombotic thrombocytopenic purpura (aTTP) therapy Cablivi, the principle asset behind its €3.9bn acquisition of Belgian biotech Ablynx last year.
The US approval – which comes a few months after Cablivi (caplacizumab) was cleared in the EU – if for the use of Cablivi in combination with plasma exchange and immunosuppressive therapy in aTTP, a rare and life-threatening autoimmune disorder that causes blood clotting and can lead to strokes and heart attacks.
Cablivi will be launched in the US later this quarter at a price of $270,000 per aTTP treatment course, before any rebates and discounts, said the company. It is the first US drug approval for Sanofi’s rare blood disorders franchise, which also includes haemophilia drugs acquired along with Biogen spin-off Bioverativ in 2018.
At the moment, despite weeks of daily plasma exchange (PEX) that can involve hours rigged up to a machine and immunosuppressive drugs, people with aTTP are still a high risk of serious breakthrough attacks that can be fatal in around 20% of cases. The disorder is estimated to effect fewer than 2,000 adults per year in the US.
“Cablivi is the first targeted treatment that inhibits the formation of blood clots,” said the FDA’s acting director of the Office of Haematology and Oncology Products, Richard Pazdur. “It provides a new treatment option for patients that may reduce recurrences.”
In the phase 3 HERCULES trial, treatment with Cablivi resulted in a significantly shorter time to an improvement in platelet counts – the primary endpoint – as well as a significant reduction in aTTP-related deaths compared to PEX and immunosuppression. The proportion of patients with a recurrence of aTTP in the study was also lower in the Cablivi group (13%) compared to the placebo group (38%). The results were published in the New England Journal of Medicine last month.
Analysts at Jefferies have suggested that Cablivi could be a game-changer in aTTP treatment and generate sales of up to $500m a year. Prior to its takeover, Ablynx had suggested peak sales of more than €1bn were possible.
Cablivi works by neutralising the blood glycoprotein von Willebrand factor (vWF), which is involved in blood clotting. In patients with aTTP, there is an accumulation of vWF that leads to clot formation in small blood vessels, which causes platelet destruction, restricts the supply of oxygen to tissues, and can lead to organ damage.
It is the first drug to be approved for marketing based on Ablynx’s ‘nanobody’ technology, a new class of therapeutic proteins based on single-domain antibody fragments.
The approval is the second big development for Sanofi in haematology this week, coming after it reported positive phase 3 results with its multiple myeloma therapy isatuximab, setting up regulatory filings later this year.