A drug company is never happy to get a “not approvable” letter from the FDA, and the one received Monday by Cambridge, MA’s Momenta Pharmaceuticals (NASDAQ [[ticker:MNTA]]) and its partner Sandoz was a doozy, coming more than two years after the firms filed for approval of a generic version of Lovenox, which had U.S. sales of $1.9 billion in 2006. But my first thought when I heard the news was, wow, the biogenerics people are going to be bummed.
The debate over biogenerics—generic versions of biotech drugs or “biologics”—is a complicated one. To get a generic version of a traditional drug approved, a manufacturer must show, essentially, that its product is chemically equivalent to the original. But guidelines that would spell out exactly what biogenerics manufacturers need to do to get their products approved have been repeatedly delayed. Opponents of biogenerics often argue that biologics—typically proteins made by genetically engineered cells, as opposed to traditional small-molecule drugs that are synthesized in a chemistry lab—are inherently too complex to be copied exactly, or even characterized completely. So approving a biogeneric, the argument goes, should require that the manufacturer conduct new clinical trials. But such trials are extremely costly; indeed, traditional generics makers can afford to offer low-cost drugs precisely because they don’t have to pay for the trials.
Momenta was founded in 2001 around technologies developed at MIT that allow for unprecedented analysis of the complex sugars that are attached to proteins during their manufacture in the cell—sugars which can profoundly affect what a protein does to the body when you inject it as a drug. The company entered the biogenerics fray on the argument that if you can completely map those sugars (along with the protein backbone, which is an easier proposition), you can in fact prove that a new drug is identical to an old one—without expensive clinical trials.
I have to admit that I’ve always found that to be a pretty compelling argument, so when I saw the words “Momenta,” “generic,” and “rejected,” in the headlines, I made the connection to bad news for biogenerics. A few other bloggers did too, evidently—ones I really admire and to whom I’m not going to link because, in this case, I think we were all wrong.
The first problem is that, though Momenta does have generic versions of biologics in its pipeline, Lovenox itself (a blood-thinner made by Sanofi-Aventis) is not a biologic. What it is is a complicated type of carbohydrate—which is where Momenta’s sugar technology comes in—derived from pig intestines. As such, the drug occupies a strange netherworld between traditional drugs and biologics. And since few drugs fall into that category, the ramifications of the FDA’s rejection of this one—and the fact that it looks like the agency might wind up requiring Momenta to conduct clinical trails of the drug if it’s to ever be approved—are limited.
Okay, but I was thinking this rejection might still bode ill for the FDA ever accepting Momenta-style analysis as a substitute for clinical trials in the approval of true biogenerics. The problem with that line of reasoning, my sources say, is that we’re just too far away from having any guidelines for approval of such drugs to even hazard a guess at what the agency might require. And with a change in the administration looming, it’s likely to take several years before guidelines are in place.
And the last way in which my initial reaction was wrong? Well, I get the impression that there aren’t that many “biogenerics people” around right now to be bummed. I don’t know if it was just bad luck, but everybody I called—folks who have in the past been very tuned in to the debate—seemed to feel that with guidelines so far off, there’s little one can say or do about biogenerics at this moment. In other words, the rejection of the Momenta drug can’t mark a setback for biogenerics because biogenerics aren’t getting anywhere in the first place.
Of course, I could be wrong.
