Who Owns Abbokinase?

Urokinase is a serine protease found naturally in the human body, specifically in urine and kidney tissue. The enzyme activates plasminogen to plasmin, which breaks down fibrin, the structural component of blood clots. Unlike streptokinase, which is a bacterial protein, urokinase is a human enzyme, making it non-immunogenic and suitable for repeated administration.

Abbott Laboratories developed Abbokinase using human neonatal kidney cells as the production source. The FDA approved Abbokinase in January 1978 for three indications: pulmonary embolism, coronary artery thrombosis, and IV catheter clearance. At the time, urokinase was one of only two FDA-approved thrombolytic agents, alongside streptokinase (Streptase and Kabikinase, approved in 1977).

Abbokinase became the most widely used thrombolytic agent in interventional radiology, particularly for peripheral thrombolysis and dialysis fistula thrombolysis. The drug's non-immunogenic nature gave it an advantage over streptokinase, which could only be administered once per patient due to antibody formation. Abbott achieved peak Abbokinase sales of approximately 274 million USD in 1998, capturing roughly 50% of the U.S. thrombolytic market.

In late 1998, Abbott notified customers of its temporary inability to ship Abbokinase. On January 25, 1999, the FDA distributed an Important Drug Warning Letter alerting physicians to manufacturing problems. The FDA's Center for Biologics Evaluation and Research had observed significant deviations from Current Good Manufacturing Practices during inspections of Abbott's facilities and BioWhittaker in Walkersville, Maryland, the sole source of the human neonatal kidney cells used in production. The FDA's concerns related to the possibility of infectious agent transmission through the kidney cell-based manufacturing process.

Shipments of Abbokinase resumed briefly but ceased entirely in March 1999. The suspension created a significant shortage of urokinase in the United States, drawing criticism from interventional radiologists who relied on the drug for peripheral thrombolysis procedures. Many practitioners contacted the FDA to express concerns about what they viewed as an unnecessarily harsh response to a potentially theoretical risk, given the drug's extensive clinical safety record.

Abbott ultimately decided to exit the thrombolytic business. In 2006, ImaRx Therapeutics acquired the urokinase assets, including approximately four years of inventory that had been held by Abbott. ImaRx rebranded the product as Kinlytic and focused on commercializing it for the treatment of acute massive pulmonary embolism. ImaRx also pursued research in microbubble technology for stroke and vascular disorders.

In 2008, ImaRx satisfied its financial obligations to Abbott and gained full unencumbered title to the urokinase assets. Later that year, Microbix Biosystems acquired the urokinase assets from ImaRx. Microbix had been interested in urokinase for over 20 years, initially planning to develop a biosimilar product. The acquisition gave Microbix the original NDA approvals, validated cell banks, and manufacturing know-how, making it the only source of low molecular weight urokinase globally.

After the acquisition, Microbix focused on identifying partners to fund the construction of a new manufacturing facility capable of supporting the relaunch of Kinlytic. The estimated cost of construction and process revalidation was at least 100 million USD, which proved difficult for a small company to secure. In May 2023, Microbix announced a commercialization agreement with Sequel Pharma LLC to reintroduce Kinlytic to the U.S. market, initially targeting the catheter clearance indication. Under the agreement, Microbix receives 5 million USD in pre-commercialization payments, up to 30 million USD in sales-based progress payments, and a double-digit royalty on net sales. Sequel Pharma funds all development costs. Sequel is expected to commence selling Kinlytic in 2028.

The catheter clearance market represents a significant commercial opportunity. Approximately 25% of central venous catheters become clogged with blood clots. The U.S. catheter clearance market is currently dominated by Roche Genentech's Cathflo Activase (alteplase), which generated approximately 342 million USD in sales in 2021. The return of Kinlytic would create a duopoly in this market, as both products have molecular and formulation complexities that make them difficult to copy.