In a decision that shows how difficult it is to copy biologics, the FDA has rejected Genzyme's request to sell a version of its Pompe disease drug, called Myozyme, which the drugmaker planned to manufacture at an additional site. But the agency ruled that any Myozyme made at the second plant should be considered a different product because of small differences in its chemical structure,The Boston Globe reports.
In order to sell the latest version of the drug in the US, Genzyme will have to file another application with new data showing the drug is safe and effective in large numbers of patients. Pompe disease is a rare, debilitating genetic illness that prevents people from breaking down a common sugar called glycogen, which can then build up in the body's cells and weaken the muscles. It affects an estimated 5,000 to 10,000 people worldwide, but Genzyme's existing production site has limited capacity, and is currently supplying the drug to 140 US patients free.
The FDA decision, however, suggests that regulators may be reluctant to approve any generic versions of biologics - often called biogenerics or biosimilars - without clinical data proving the drugs are at least as safe and effective as the originals if there are even slight differences in the compounds. As a result, Genzyme will have to file a separate Biologics License Application to win approval. (Here's the Genzyme statement).
"It sends a very loud message and sets a very high bar," Alison Lawton, Genzyme's senior vice president for regulatory affairs, tells the Globe. And she notes that Genzyme had the advantage of having full access to all the original information about the drug and still had trouble replicating the manufacturing process exactly.
While traditional "small molecule" drugs, like aspirin, are usually mixed from chemicals, biologics are made from living organisms and considered much harder to replicate. Myozyme, for instance, is based on specially designed proteins grown in Chinese hamster ovary cells, the paper writes.
In this case, Genzyme says the FDA was concerned about slight differences in the carbohydrate structures of the molecules. To make sure the differences weren't important, the FDA demanded data from larger numbers of patients that proves the version made in the larger plant is safe and effective. So far, Genzyme says it has submitted data only from a very small number of patients, making it hard to tell whether the molecular differences were significant.