Researchers at Robert Linhardt of the Rensselaer Polytechnic Institute and Jian Liu of the University of North Carolina at Chapel Hill say they have discovered an entirely new process to manufacture ultra-low molecular weight heparin. The study, published in the Oct. 28 edition of the journal Science, shows that the drug is identical in performance and safety to the current and successful anticoagulant fondaparinux, but is purer, faster, and less expensive to produce.
Fondaparinux, sold as a name-brand drug and also recently approved by the FDA as a generic drug, is a synthetic anticoagulant used to treat deep vein thrombosis, with more than $500 million in annual sales. It is part of the family of heparin drugs. But, unlike most heparin products, it is chemically synthesized from non-animal materials. All other heparin-based drugs currently on the market use materials from the intestines of pigs and lungs of cattle as source materials. Such animal materials are more likely to become contaminated, according to Linhardt.
"When we rely on animals, we open ourselves up for spreading viruses and prion diseases like mad cow disease through the use of these heparins," Linhardt said. "And because most of the raw material is imported, we often can’t be sure of exactly what we are getting."
The new process uses chemicals and enzymes to reduce the number of steps in production of fondaparinux from approximately 50 steps down to just 10 to 12. In addition, it increases the yield from that process 500-fold compared to the current fondaparinux process, and could decrease the cost of manufacture by a similar amount, according to Linhardt. The new process also reduces the amount of waste produced.
Linhardt and Liu have already begun testing the drug in animal models with successful results and think the drug could be quickly transferred to the market.
"This research represents an entirely new paradigm in drug manufacturing," Linhardt says. "With this discovery, we have successfully demonstrated that replacing the current model of drug production with a chemoenzymatic approach can greatly reduce the cost of drug development and manufacturing, while also increasing drug performance and safety, and reduce the possibility of outside drug contamination. It is our hope that this is the first step in the adoption of this method for the manufacture of many other drugs."