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Generic Lovenox & An FDA Precedent: Pan Explains
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By Ed Silverman // July 30th, 2010 // 9:35 am

Last week, the FDA issued one of those surprise product approvals by giving a thumbs up to a generic version of Lovenox, a widely used bloodthinner sold by Sanofi-Aventis, much sooner than most people expected (see here and here). The move is something of a game-changer for the pharmaceutical industry and so we spoke briefly with Jonathan Pan, a senior associate at the Scientia Advisors consulting firm, about the implications…

Pharmalot: Why is this approval such an important development?
Pan: Well, it’s a $4 billion product for Sanofi-Aventis. That’s one reason it’s important. The second reason is the active ingredient is an extremely complicated molecule – a macro molecular that wraps around itself – which means it’s hard to characterize and hard to manufacture. So it requires a lot of technical expertise. Sanofi’s argument is that it’s too hard to make, that you can’t make the same exact molecule, although that argument is the same one that everyone makes about their biologic product…However, Lovenox is not a biologic like a protein or antibody. It’s much simpler but still relatively complex…Momenta and Sandoz somehow convinced the FDA that their product is equivalent in safety and efficacy to the original product without the need to fully characterize the structure and sugar changes in the active molecule.

Pharmalot: And there’s still no framework for approval.
Pan: Since there is no framework for regulatory approval for a biosimilar…the FDA is creating a precedent for a regulatory process…What’s most interesting is that, for a traditional small molecule, all I need to prove is that the chemical entity is equivalent and I can make an equivalent product. But this particular compound, which is a little more complex than a simple molecule with a fixed structure, is difficult to prove equivalence. So the FDA had to use some other proxy. What the FDA did was ask Sandoz and Momenta to create a robust clinical trial, although it was not as extensive as going through all three phases for a new product approval, but not as lacksadaisical as a small molecule generic. What people are trying to look at now is how much clinical trial work do I need to do without having to do all three phases? What is the minimum threshold on my product in order to show the FDA it’s equivalent to the original marketed product?


Pharmalot: What are the implications for all the players?
Pan: Until now, there have been assumptions that biologics may be too complex to characterize or understand. So there were barriers to entry. The companies, basically, saw this as a door to close off potential entrants to their markets and a means to extend the life of their products beyond the patent years….In this case, it’s not as though a purely generic company is manufacturing this. It’s really Novartis (which owns Sandoz). The large pharmas are also invested in this game to compete against each other… There is one caveat –Sandoz and Momenta filed this particular application under an ANDA. It’s almost a Paragraph IV filing in order to get a generic product. And the FDA doesn’t consider this class of product to be a biologic. So technically, it’s not a follow-on biologic. But what’s interesting is that using this particular route of approval creates a precedent for building out infrastructure for creating a follow-on or biosimlar approval process as mandated by health care reform. So if you’re a big pharma, you need to pay attention to that, of course.

Pharmalot: How so?
Pan: There are a lot of diff strategies one can employ…To protect themselves, bi g pharma will use the traditional protection process. They will create patent barriers either through new product formulations, new dosage formulations, new indications that are part of the labeling that grants exclusivity. Instead of saying a product is too complex to manufacture, I think the issue is coming down from the high clouds to the realm of a small molecule situation, where pharma companies have to play the old-fashioned line extension game.

Pharmalot: Are we likely to see many more, if not a flood of follow-on products now?
Pan: There were three different companies - Amphastar,Teva and Momenta - attacking the same point, and from what I hear, Teva is almost on the cusp of filing their particular product. As far as whether, this will be a floodgate, there may be a trickle at first. Once people understand the process. I think post-2012, most companies are going to start thinking about follow-on biologics…Remember, there are follow-on products elsewhere in the world. The US is unique. We don’t have the regulatory pathway allowing biosimilars. Epogen, for instance, is approved in Europe….
Most of the biologic patent expirations are coming in the next five to 10 years and to develop the infrastructure for those products, we’re in the right time for that now. It takes roughly five years to get a product on the market…so this is the perfect time for everybody in the market to start thinking about getting in the game. By then, the regulatory framework will likely be in place. Companies should be looking at this and gearing up for what eventually will be an avalanche that is coming…

Pharmalot: By the way, Is there any reason to think Sanofi might prevail in its lawsuit to stop the generic? (background here)
Pan: If I were the judge sitting on this case and thought Sanofi had a case, I probably would have enacted an injunction until Aug. 17, when the proceedings are to begin. So that tells me that at least the judge seems to indicate the FDA made a reasoable determination of equivalency of safety and followed guidelines for the generic approval process. I think Sanofi had no choice but to file the suit. It only makes good business sense and any delay they win is an obvious benefit for them. But the generic has more or less gained some traction in the market. I can’t predict which way it will go, but Sanofi’s argument may not hold water…
http://www.pharmalot.com/2010/07/generic-lovenox-and-an-fda-precedent-pan-explains/?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+Pharmalot+%28Pharmalot%29