Approval of first-time generic Lovenox is followed by lawsuit

Sandoz, the generics division of Novartis, is the first U.S. company to receive FDA approval to market a generic version of the leading hospital-based medication, Lovenox (enoxaparin sodium), the “gold standard” in anti-thrombotic treatment. No sooner did Sandoz begin shipping its generic version than Sanofi-Aventis, manufacturer of Lovenox, filed a federal lawsuit to reverse the FDA’s approval of the generic. Last year, Lovenox recorded $4.57 billion in sales for Sanofi-Aventis, according to IMS Health. Both the new generic and Lovenox are low-molecular-weight heparin anticoagulants that help prevent deep vein thrombosis.

Randy Vogenberg, PhD

“Generic enoxaparin has the potential to bring hundreds of millions of dollars of savings to the U.S. healthcare system and in turn, to payors and consumers,” Sandoz U.S. has stated.

In an effort to protect its widely used branded drug, Sanofi-Aventis is challenging the safety of the new generic version and questioning whether FDA failed to ensure that the product has the same active ingredients as Lovenox, a complex mixture of sugar molecules derived from pig intestines. The drugmaker also claims that FDA approved enoxaparin through an abbreviated new drug application (ANDA) rather than through a new drug application (NDA), as would be the case for a completely new drug. An ANDA application allows for interchangeability of a product without a head-to-head clinical trial being conducted.

“Sanofi-Aventis is concerned by potential implications for patient safety since the product approved today has not been subjected to extensive clinical trials to demonstrate its efficacy and safety as Sanofi-Aventis has done with its product,” said the company in a press release.

FDA had requested that Sandoz and Momenta Pharmaceuticals, a partner in the development of the generic product, conduct a robust clinical trial, one not so extensive as an NDA trial. Sandoz underwent a rigorous 5-year FDA approval process for enoxaparin and is confident in the FDA's actions, said the company.

In response to the lawsuit seeking a temporary restraining order, the U.S. District Court for the District of Columbia set a preliminary injunction hearing for Aug. 17, 2010, naming FDA Commissioner Margaret Hamburg and Health and Human Services Secretary Kathleen Sebelius as defendants. In the interim, the court has not restricted sales and shipment of the new generic.

In 2003, Sanofi-Aventis (then Aventis Pharmaceuticals) filed a citizen petition requesting that any generic version of Lovenox be equivalent to the blockbuster branded drug. It also requested proof that the manufacturing process be equivalent, or show equivalent efficacy and safety in clinical trials. FDA accepted the first condition but said it was unnecessary for a company with a generic product for Lovenox to demonstrate fulfillment of the other requests for equivalency.

Sanofi-Aventis anticipates that its core earnings will be flat or drop by 4% this year as a result of the approval of generic enoxaparin. The company had estimated an increase of 2% to 5% for 2010.

Further complicating matters, Teva Pharmaceutical Industries Inc., which is concerned that FDA will approve a generic version of its multiple sclerosis drug, Copaxone, is seeking approval for a generic Lovenox.

Test case for biosimilars?

With debate continuing over whether Lovenox is considered a “true” biological drug, the approval of the new generic may not be a suitable test case for future FDA approvals of biosimilars. The new Patient Protection and Affordable Care Act provides for an approval pathway for biosimilars.

“[Lovenox’s] approval has a harbinger of strategy contained in it that indicates the new healthcare reform legislation, which created the opportunity for an abbreviated biologics license application, may be a moot point,” said Randy Vogenberg, PhD, principal at the Institute for Integrated Healthcare in Sharon, Mass.

“From an employer or other payer perspective, cost savings for biologic products of any complexity will remain elusive, owing to realities of the marketplace and manufacturer production economics,” he added.

Vogenberg said that estimates of “savings” for U.S. biosimilars from all pathways will be in the range already seen in other countries - from 15% to 20% on average. “At $2,500 per month, savings of any amount is of value but hardly the perceived savings trumpeted during the health reform debate,” he said.