This is a fascinating development in the debate about the potential pathway for generic biologics. Other companies have also experienced problems manufacturing their own drugs in different locations. There will certainly be a pathway for FDA approval eventually. However, the key issue remains as to whether a generic producer should have to replicate the clinical trials process to prove patient safety is still up in the air...
FDA rejects Genzyme request for Myozyme
By Todd Wallack, Globe Staff | April 22, 2008
In a decision that shows how difficult it is to copy complex, biologic drugs, federal regulators rejected Genzyme Corp.'s request for permission to sell in the United States a version of its Pompe disease drug, called Myozyme, that is made at its Allston manufacturing plant, the company disclosed yesterday afternoon.
Though Genzyme already has permission to sell batches of Myozyme manufactured at its smaller Framingham plant, the Food and Drug Administration ruled that Myozyme made at the Allston plant should be considered a different product because of small differences in its chemical structure, Genzyme said.
In order to sell the Allston version of the drug in the United States, Genzyme said it will have to file another application with new data showing the drug is safe and effective in large numbers of patients.
Because it was already preparing to submit such data anyway, Genzyme said it believes it probably will be able to start selling the Allston-made drug early next year.
"We are disappointed by the decision because it will delay access to Myozyme in the United States," said Genzyme Corp. chief executive Henri Termeer in a conference call with analysts.
Specifically, Genzyme believes the decision will reduce its revenue by $45 million this year and cut its earnings by 10 cents a share. Because the Framingham plant has only limited capacity, it is currently supplying the Allston drug to 140 US Pompe patients free. 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.
Termeer said he believes the FDA decision will be only a temporary financial setback. The company said it had been preparing to give the FDA positive data collected from 900 patients who are already taking the Allston-made drug. In addition, more than 40 countries have approved Myozyme made at the larger plant.
But the FDA decision also suggests that regulators may be reluctant to approve any generic versions of biologic drugs - 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.
"It sends a very loud message and sets a very high bar," said Alison Lawton, Genzyme's senior vice president for regulatory affairs. Lawton noted 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, biologic drugs 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.
In this case, Genzyme said the FDA was concerned about slight differences in the carbohydrate structures of the molecules. To make sure the differences weren't important, executives said 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 said it has submitted data only from a very small number of patients, making it hard to tell whether the molecular differences were significant.
The FDA did not a return a call seeking comment.
Congress is currently considering at least two bills to create a process to let drug makers market generic versions of biologic drugs, such as those made by Genzyme and many other biotechs.
But lobbyists disagree about how long brand-name drug makers should be entitled to exclusive rights to their drugs before facing generic competition, as well as how difficult the approval process should be.
Most specialists believe some version of the legislation, however, will likely be adopted by the end of 2009, making the FDA ruling relevant.