Karl Thiel recently interviewed Craig Wheeler, CEO of Momenta Pharmaceuticals (NASDAQ:MNTA), a Rule Breakers recommendation. Read on for the inside take on getting M-Enoxaparin through the regulatory process, competitors' products, and more.

Karl Thiel: Can you briefly describe Momenta and your lead product candidate, M-Enoxaparin?

Craig Wheeler: Momenta Pharmaceuticals is a biotechnology company specializing in the detailed structural analysis of complex mixture drugs. We're applying our technology to the development of generic versions of complex drug products, as well as to the discovery and development of novel drugs. Momenta was founded in 2001 based on technology initially developed at the Massachusetts Institute of Technology and is headquartered in Cambridge, Mass.

Our most advanced product candidate, M-Enoxaparin, is designed to be a technology-enabled generic version of Lovenox, a low-molecular-weight heparin (LMWH) product. Lovenox is the most widely prescribed LMWH used for the prevention and treatment of deep vein thrombosis [blood clots] and is also used in the treatment of acute coronary syndromes (ACS). Sanofi-Aventis (NYSE:SNY) reported worldwide sales of Lovenox of approximately $3.2 billion in 2006, with approximately $1.9 billion coming from the United States.

Our ability to sequence and analyze complex mixtures of sugars has allowed us to analyze Lovenox and develop a process that we have used to make a generic version of Lovenox that we believe will meet the FDA requirements for approval through the abbreviated New Drug Application (ANDA) process. We have collaborated with Sandoz, a division of Novartis (NYSE:NVS), to jointly develop, manufacture, and commercialize M-Enoxaparin in the U.S. and the European Union.

M-Enoxaparin and the approval process
When do you think M-Enoxaparin will be approved? More specifically, is the FDA questioning consistent with concerns about biosimilarity, or is it more about manufacturing?

Wheeler: For generic drugs, there is no fixed timetable for approval or PDUFA date. Due to the imprecision of forecasting FDA timelines for generic drugs, we are not going to speculate on when the FDA might act on our application. We have responded to the questions from the FDA's Office of Generic Drugs in what we believe is a complete and thorough manner and believe our ANDA is on track for approval.

Regarding the nature of any questions from FDA, we don't comment on the specifics of our interaction with the agency. However, concerning biosimilarity, I will say that to date, the FDA has not considered heparins to be a biologic. Therefore, if chemical equivalency to Lovenox is demonstrated, then we believe it is unlikely that demonstrating bioequivalence will be an issue.

Thiel: There seems to be a lot of momentum to create a regulatory track for "follow-on proteins" -- something Momenta has testified about before Congress. Any thoughts on the compromise Senate legislation created by Sens. [Ted] Kennedy, [Orrin] Hatch, and [Hillary] Clinton?

Wheeler: Overall, we are encouraged by the draft legislation. In our opinion, the version passed by the Senate HELP [Health, Education, Labor, and Pensions] committee was constructive. There were two key provisions that we were pleased with. First, clinical trials for follow-on biologics (FOBs) are not mandated, leaving decisions regarding the need for clinical studies to be at the discretion of the FDA. Second, the HELP committee version provides a pathway for interchangeability.

It is not clear whether FOB legislation will be passed this year, but regardless of the timing, we are continuing to work on follow-on biologics, both with our partner Sandoz as well as through continued investment in our glycoprotein technology.

Competing products
Thiel: In the past, you've cited observations that rival versions of enoxaparin created by Teva (NASDAQ:TEVA) and Amphastar show different peaks in a chromatogram and are likely to be substantially different from the Aventis reference drug.

If Teva and Amphastar eventually manage to characterize Lovenox, how much can they change their ANDAs before they're considered new applications and they lose first-filer status? In other words, if improvements in characterization lead them to discover the drugs are not structurally similar but they change their drugs on the basis of new discoveries, can they keep their priority status? Is that a concern, given the delays?

Wheeler: We have not seen any data on Teva's product. Data on Amphastar's product was made available in a public response memo to the FDA dated May 2004. In that document, differences on mass spectra were noted between Amphastar's product and Lovenox. That data may no longer be current, so we cannot provide comment on how the products compare today.

ANDAs can be amended consistent with the FDA's 505j regulations. As long as amendments are within the same ANDA filing, we don't believe that first-filer status will be changed.

Thiel: Competing heparins such as Pfizer's (NYSE:PFE) Fragmin and Pharmion's (NASDAQ:PHRM) Innohep have relatively small sales. Aventis dominates the U.S. market with Lovenox, and it would seem that Momenta's success will ride on whether M-Enoxaparin is really regarded as equivalent. A Hatch-Waxman [Act] approval would presumably let you put forward the drug as such, while proposals for "follow-on" biologics would limit claims of substitutability.

Wheeler: If M-Enoxaparin is approved as AB-rated under the 505j pathway, then it will be considered interchangeable with the branded product. If generic enoxaparin sodium were to be reclassified as a biologic, there's presently no regulatory pathway for approval.

Thiel: Do you plan to market M-Enoxaparin as essentially a generic, or might there be a further need for clinical studies to demonstrate to doctors that it really is a substitutable product?

Wheeler: Yes, our expectation is that M-Enoxaparin will be approved as an AB-rated generic version of Lovenox and that it will be marketed as directly substitutable. Although data from pharmacokinetic studies in healthy volunteers were part of the ANDA package for M-Enoxaparin, clinical studies designed to evaluate safety and efficacy in patients are not required or even allowed under the 505j pathway.

Looking ahead
Thiel: Would you consider taking legal action against the FDA, as Sandoz did with Omnitrope, to force action?

Wheeler: At the present time, we believe the review of our ANDA is still on track and is progressing satisfactorily. Should that belief change in the future, we will work with our partner Sandoz to decide the appropriate next steps.

Thiel: Any final thoughts you'd like to leave with investors?

Wheeler: I'd like to point out that while M-Enoxaparin represents a tremendous opportunity for Momenta and is of strong interest to investors, we also have an emerging pipeline worthy of attention. In our short history, we have managed to rapidly leverage our technology to create a pipeline consisting of both complex generics such as M-Enoxaparin and M356 as well as novel drug candidates such as M118, which is designed to provide anticoagulation therapy to patients with ACS. We are also advancing our oncology product candidate that is in the discovery phase. I'd like to reinforce that we have an innovative technology platform at Momenta that can be applied across multiple therapeutic areas and the full span of drug discovery and development.

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