After a five year wait, the US Food and Drug Administration announced last Friday that it has finally approved a generic form of the blood thinner, Lovenox. The move has been widely anticipated as a key first step towards US approval of generic copies of biologic drugs, such as therapeutic proteins.
US regulators have been grappling for years with how to handle generic biologics, often called ‘biosimilars’. Because biologics are so complex, some have argued that it is impossible to copy them exactly, raising the question of how much safety data should be collected on biosimilars before they are approved. (For more, see ‘US health bill promises changes for biomedical researchers’ and ‘Bills target biosimilar drugs’. )
Lovenox is a complicated mixture of sugar molecules made by breaking apart long carbohydrate chains often harvested from pig intestines. The FDA does not consider Lovenox to be a biologic drug, so the generic’s makers – Momenta Pharmaceuticals based in Cambridge, Massachusetts, together with Sandoz, Novartis’ generics arm – were able to file for approval using the standard generics pathway.
Nevertheless, the drug is highly complex – its maker, Sanofi Aventis, once claimed that it was impossible to even identify all of its components, much less copy them – and industry insiders have looked to the drug’s status at the FDA as a bellwether of the agency’s stance towards complex generics like biosimilars. (For more on this, see ‘Biotechs go generic: The same but different’.)
Furthermore, Momenta hopes to use its generic Lovenox as a demonstration of the carbohydrate wizardry the company will bring to bear on developing biosimilars, which will likely require precise characterization of the sugars attached to therapeutic proteins.
The drug has also been a source of controversy. In 2009, a competing company called Amphastar Pharmaceuticals charged that Janet Woodcock, director of the FDA center that oversees drug approvals, was unfairly favoring Momenta. Amphastar, which filed for approval of its Lovenox copy in 2003 (two years before Momenta), complained that Woodcock had appointed a Momenta founder to lead an FDA task force, and had even coauthored a paper with Momenta scientists. The accusations culminated in several investigations– one launched by the Department of Health and Human Services’ inspector general, the other carried out by a private investigator hired by Amphastar to track Woodcock’s travels and dig up personal information about her family (WSJ, subscription required).
The FDA dismissed Amphastar’s complaint earlier this year, noting that Woodcock had recused herself from considering the Momenta and Amphastar filings.
UPDATE – Sanofi-Aventis has now gone to court in an attempt to block the FDA ruling. See Reuters for more.
Update: SanofiAventis has sued the FDA for approving Lovenox, claiming that the agency overlooked ample data showing the importance of even minute variations in the drug’s composition. Lawsuit documents are posted on the Pharmalot blog.