FDA Explodes ZymoGenetics' Recothrom Safety Argument

Implications: The FDA -- likely with encouragement of King Pharmaceuticals -- has ordered ZymoGenetics to cease dissemination of materials that cite "a significantly lower incidence of antibody formation compared to the commercially available bovine thrombin product [Thrombin-JMI]." "This statement is false or misleading because it suggests that Recothrom is safer than the bovine thrombin product due to a lower incidence of antibody formation," while in fact "the incidences of pre-specified adverse events were similar between Recothrom and bovine thrombin" in a head-to-head clinical trial conducted by ZymoGenetics. Shortly after the U.S. approval of Recothrom was announced in January, I posted an analysis that concluded as follows:  "While ZymoGenetics deserves kudos for crossing the FDA finish line, its selling proposition is flawed." One of those flaws was the company's fast and loose promotion of this antibody safety claim.  The FDA's action comes as no surprise.

Analysis: In my Jan. 18 analysis just after Recothrom was approved, I said "ZymoGenetics will do its level best to emulate the achievements of all the other new recombinant versions of plasma-derived therapeutic proteins:  knock them down or entirely out of the market with a superior safety claim."

The company has aggressively pushed the point that Recothrom demonstrated much lower immunogenicity than Thrombin-JMI in Phase III human testing. 

Unfortunately, there wasn't a shred of evidence that antibodies generated against bovine proteins in Thrombin-JMI translate into clinical complications.   They might, but not in a broad surgical patient population like the one enrolled in the pivotal Recothrom trial.

ZymoGenetics' star safety claim for Recothrom has just been thrown out of the game.  To continue the metaphor, remaining safety arguments -- lack of a black box warning or a warning related to potential transmission of an infectious agent -- are benchwarmers by comparison.