Drug companies looking to bring biosimilars to the U.S. market will use existing regulatory pathways like 505(b)(2) or an outright Biologics Licensing Application over a new regulatory pathway provided in the health care reform legislation because of provisions in the new pathway that favor brands, Jeff George, the head of Sandoz, predicted.

Novartis' generic unit has been at the forefront of efforts to advocate for biosimilars, both in the U.S. and Europe (¹ Also see "Paving the Critical Path for Innovation in the Biotechnology Industry" - Pink Sheet, 1 February, 2006.).

Sandoz has already launched three biosimilars in Europe and even brought one follow-on biologic to the U.S. - the human growth hormone Omnitrope , which was approved under the 505(b)(2) pathway, a framework that allows for drug applications to reference safety and efficacy data of previously approved drugs.

The passage of health care reform legislation paved the way for the establishment of a regulatory framework for biosimilars in the U.S., which could open the door to low-cost versions of biologics, including drugs like Amgen/Pfizer's Enbrel , Lilly's insulin Humalog and Amgen's Neupogen (² Also see "On The Cusp Of Biosimilars: Reform Ushers In Next Generic Drug Era" - Pink Sheet, 29 March, 2010.).

Generic drug makers applaud passage of the legislation, but some, including Sandoz, are under-whelmed by the opportunity the legislation provides. Not that the final outcome came as a big surprise; generic drug companies had expressed concern over several of the proposals as the legislation was winding through Congress.

"The devil's really in the details," George said in an interview. While he said Sandoz supports several elements of the legislation, including the authority granted to FDA to determine the data requirements for biosimilar applicants, he noted, "There are two key issues that we think ... will be hurdles to bringing biosimilars to the market."

Too Much Information

One of the controversial elements for Sandoz is a provision that would require a biosimilar drug maker to give its application to the innovator company to facilitate patent infringement negotiations. Under the current laws governing small molecule drugs, generics companies don't hand off abbreviated new drug applications to brand drug makers after they are submitted to FDA. Nonetheless, much of the information does become available through patent infringement proceedings. The health care reform legislation requires that generics applicants provide the reference product sponsor with a copy of the application and "other information that describes the process or processes used to manufacture the biological product" within 20 days after FDA accepts the application for review.

The reference product sponsor is then expected to provide the biosimilar applicant with a list of patents for which it thinks it could claim patent infringement, and each company is expected to lay out its legal basis and ultimately negotiate and reach a resolution on which patents to litigate.

That gives innovator companies an upper hand, Sandoz contends. "I think it is unfair to generic companies that we would be required to hand over our dossiers to our competitors years before the product comes to market in order that they could pick apart our arguments scientifically and on the patent front to leverage in their own litigation against us," George said.

Sandoz had been a vocal opponent of the data sharing issue well before the legislation was passed (³ Also see "Follow-On Biologics' Other Pathway: Mechanisms To Resolve Patent Disputes Vary In Legislation" - Pink Sheet, 2 November, 2009.).

Brand biotech companies, for their part, seem equally concerned about how the patent challenge and data sharing provisions will play out (see ⁴ Also see "Biosimilars Pathway Has Blind Spots As FDA And Firms Begin Roadwork" - Pink Sheet, 3 May, 2010.).

Litigation Uncertainty

A second issue, according to Sandoz, is that the legislation does not require litigation resolution, opening the door to years of patent litigation, even after a biosimilar is approved by FDA.

"Effectively, it calls into question why you would use this pathway if you've got to hand over your scientific dossier to your competitor on the one hand and your competitor can tie you up in litigation," George said.

"With that kind of pathway, it's not clear that companies like Sandoz and the leading generic companies in the world would use this pathway to go to market," he added.

The potential for savings from biosimilars is an important element of the health care reform legislation intended to reduce health care spending. In the U.S., $15 billion in brand biologics are expected to go off patent between 2009 and 2013, according to IMS Health.

Teva has already opted to seek approval of a biosimilar in the U.S. using a traditional BLA. The company filed its first BLA in December, well before the new law was signed, for the granulocyte colony-stimulating factor XM02 for chemotherapy-induced neutropenia. The drug would compete against Amgen's Neupogen (⁵ Also see "Teva, Eyeing Follow-Ons For Most Biologics, Starts With Amgen's Neupogen" - Pink Sheet, 7 December, 2009.).

BLAs are a route the company would consider for future applications as well, President and CEO of Teva North America Bill Marth said. "As the FDA determines the process for filing an abbreviated BLA, we will continue to evaluate what pathway we take on a protein-by-protein basis," he said in an email exchange.

Teva's main issues with the legislation are the 12 years of exclusivity awarded to brand drug makers and provisions that allow for so-called "evergreening," which the firm maintains would provide additional exclusivity for minor modifications to an existing drug.

"If Congress' intention is to create a robust and competitive biosimilars market, the current provisions of the law on exclusivity and evergreening must be revisited," Marth said.

- Jessica Merrill ( ⁶ j.merrill@elsevier.com )

Sandoz Will Steer Clear Of U.S. Biosimilars Pathway, Use Other Applications

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