Editor

Momenta Pharmaceuticals Inc.'s surprising good fortune with the FDA's nod last week for the company's generic Lovenox sent shares skyrocketing 82 percent and capped five years of exchanges between the regulatory agency and Momenta with partner Sandoz, the generic unit of Basel, Switzerland-based Novartis AG. It also may have sent an ominous signal to Teva Pharmaceuticals Inc.

Cambridge, Mass.-based Momenta and Sandoz have had a generic version of Petach Tikva, Israel-based Teva's multiple sclerosis therapy Copaxone (glatiramer acetate) lingering at the FDA for the past two years, and it's a drug as chemically complex as Lovenox (enoxaparin), the anticoagulant derived from the blood thinner heparin.

The Momenta/Sandoz generic version of Lovenox, sold in the branded form by Paris-based Sanofi-Aventis Group, is the only pending contender that squeaked past the FDA's tight standards for a generic, only made tighter by heparin contamination issues in China, where several deaths took place. Just as problematic for Momenta/ Sandoz was the high bar of "sameness" that the generic version had to reach, once the agency determined it would take the issue on at all.

Teva itself was among those to file for approval of generic Lovenox a few years ago, along with Rancho Cucamonga, Calif.-based Amphastar Pharmaceuticals Inc. When, in 2007, the FDA turned thumbs down on the Momenta/Sandoz's filing, citing a failure to convince regulators about the risk of immunogenicity, but the companies put together a bigger data package, leaving other applicants to chew their nails and wait. (See BioWorld Today, Nov. 7, 2007.)

The victory with the FDA approval means big things for Momenta with its now-proven sugar chemistry platform. Momenta stands to get fat royalties - about 45 percent - if no other generic Lovenox gets past the gate, and that's plenty of revenue since branded Lovenox sold $4 billion worldwide and $2.5 billion in the U.S. last year.

Leerink Swann, based on the FDA's approval of an "A-rated" (i.e., fully substitutable) generic Lovenox, dropped revenue estimates for Sanofi while "[assuming] multiple generics will ultimately be approved." Analysts lowered Lovenox U.S. revenue by €540M (about US$706 million) this year and as much as €1 billion in the out years, translating into an earnings-per-share reduction of €0.25 and €0.31-€0.51 in each of the respective periods.

Woe to Sanofi, as a potential takeout candidate, Momenta's sitting pretty, with another promising anticoagulant in the pipeline, M118. The compound not long ago met its Phase II endpoint of reducing cardiovascular events, bleeding and use of rescue medicines. The firm has M402, a heparin sulfate glycosaminoglycan mimetic for cancer, at the preclinical stage.

The strategy of larger drug developers to establish their own generic departments began to look even smarter with the FDA's latest move, though Sanofi naturally didn't take the approval of Lovenox lying down, and promptly submitted filings in federal court, asking that the FDA withdraw the marketing clearance. A hearing on the bid for a preliminary injunction is slated for August 17.

Few expect the Sanofi legal effort to block generic Lovenox will have much effect, especially given how carefully the FDA considered the compound. If anything, court deliberations may only highlight the features of the Momenta/Sandoz drug that persuaded the FDA. But Sanofi is giving it a college try, calling the agency's action "arbitrary and capricious and otherwise unlawful," alleging further that the FDA "ignored its own precedent" regarding the approval of generic compounds and "exceeded its authority."

The court papers specifically target Section 505 (j) (2) (A), which, Sanofi said, does not allow the FDA to ask for more safety and efficacy data on generic products such as Momenta/Sandoz propose. Yet the agency did ask for more data, and apparently gave the blessing to the new M-enoxaparin on the basis of it. Doing so "effectively allows the generic applicant to rely upon the pioneer's confidential commercial information in a manner not contemplated by the statute."

Also argued in the Sanofi lawsuit: The FDA dismissed "without any rational justification or analysis, a wealth of scientific evidence establishing that small variations in the manufacturing process used to create low molecular weight heparins such as Lovenox can result in significant changes to the structure and pharmacological properties of generic versions."

Onlookers seem mostly to believe that the agency's long scrutiny of the Momenta/Sandoz application means the approval is largely bulletproof. Maybe so, but the out-of-left-field approval raised some eyebrows, and more unexpected events could be around the corner.

Another player in the generic Lovenox game is Watson Pharmaceuticals Inc., of Morristown, N.J., which submitted its abbreviated new drug application in March 2003 and in 2005 entered a deal with Ft. Lauderdale, Fla.-based Andrx Corp., giving Andrx marketing rights to about 30 percent of Lovenox sales in the U.S. retail pharmacy market. At the time, Watson already was the target of a patent infringement lawsuit by Aventis (later to become Sanofi-Aventis Group).

Watson and Teva, which suffered some on Wall Street as a result of the FDA decision, became the subject of a Piper Jaffray research memo in which analyst David Amsellem - echoing others who debated the issue in print - opined that the agency "is unlikely to approve Teva and/or Watson's aNDA filings on Lovenox down the road," though most on Wall Street had not included revenue from the drugs in their models anyway.

Meanwhile, rumblings that Sanofi might buy out Genzyme Corp. gave the latter's stock a boost and encouraged Sanofi investors, wanting backfill for the pipeline, not to mention help when generic Lovenox begins eating away at those revenues. Genzyme already was on the comeback trail after a proxy fight with billionaire investor Carl Icahn. The firm was plagued by a shortfall of enzyme replacement therapies Cerezyme (imiglucerase alfa) and Fabrazyme (agalsidase beta) that hurt earnings for the past three quarters and sparked a fine from the government. Genzyme had gained enough confidence lately that it had little interest in would-be suitors - but, especially with the latest Lovenox news, Sanofi is strongly motivated to try overcoming such resistance.