Staff Writer

Momenta Pharmaceuticals Inc. and partner Sandoz Inc. said the FDA accepted their abbreviated new drug application for M356, a generic version of peptide-based multiple sclerosis drug Copaxone (glatiramer acetate, Teva Pharmaceuticals Inc.).

Although the FDA has approved abbreviated new drug applications (ANDAs) for protein-based drugs before, it hasn't approved one with such variability of composition and complexity of manufacturing as Copaxone, said Biren Amin, analyst with Stanford Group Co.

Copaxone is a mixture of peptides with variable molecular weight and sequence. Although it was approved under a new drug application and not a biologics license application, Amin called it a "pseudo-biologic" because it has "similar characteristics" to a biologic.

Congress continues to debate the creation of an abbreviated regulatory pathway by which the FDA could approve follow-on biologics (FOBs) without requiring a full complement of clinical trials. Five bills have been introduced by lawmakers, with varying opinions on what studies would be required to prove bioequivalence, whether follow-on products would be substitutable for originals, and how long innovator companies should enjoy data exclusivity. (See BioWorld Today, April 30, 2008, June 23, 2008, and June 27, 2008.)

Follow-on proteins to gain FDA approval - including Omnitrope (somatropin [rDNA origin], Sandoz GmbH), Fortical (calcitonin salmon recombinant, from Unigene Laboratories Inc.), GlucaGen (glucagon recombinant, from ZymoGenetics Inc.), and others - have used the 505(b)(2) pathway, which involves referencing clinical trials not conducted by the sponsor. (See BioWorld Today, June 1, 2006.)

Momenta and Sandoz are seeking approval of M356 under the 505(j) pathway, which instead relies on the agency's previous finding that the listed drug is safe and effective.

On a conference call, Momenta President and CEO Craig Wheeler refused to say whether or not the company had conducted any clinical trials with M356. Amin said the vagueness is designed to avoid providing competitors with a blueprint for a potential regulatory pathway, although he guessed that Momenta and Sandoz "probably have" conducted trials.

Generic manufacturer Mylan Inc. also has stated an interest in pursuing generic Copaxone.

Teva holds seven patents on Copaxone that do not expire until 2014, but Momenta and Sandoz have included a paragraph IV certification in their filing, which asserts that the patents are invalid, unenforceable, or will not be infringed. Wheeler acknowledged that Momenta will need to defeat all seven patents to market its drug.

In return, Teva issued a statement announcing plans to file a patent infringement lawsuit against Momenta and Sandoz.

Teva also said that the "variability and complexity of the composition of the polymers makes any attempt to replicate this formulation extremely difficult at best" and that typical bioequivalence studies would be "meaningless" because the drug is broken down rapidly.

Wheeler maintained that Momenta has "thoroughly characterized" the drug and reverse engineered a product that "we believe is equivalent to Copaxone."

Shares of Cambridge, Mass.-based Momenta (NASDAQ:MNTA) rose 81 cents to close at $13.89 on Friday. Shares of Jerusalem-based Teva (NASDAQ:TEVA) fell $3.22 to close at $41.78.

Amin predicted that the regulatory review process for generic Copaxone products will be "a long, drawn-out process." He likened it to what has occurred with ANDAs for generic Lovenox (enoxaparin, Sanofi-Aventis Group), another product he classified as a pseudo-biologic.

Teva, Momenta and Amphastar Pharmaceuticals Inc. all have filed ANDAs for generic versions of Lovenox, but after about five years of going back and forth with the agency, an approval has yet to be achieved.

Last year, the FDA rejected the ANDA from Momenta and Sandoz, saying that the companies failed to adequately address the drug's potential for immunogenicity. The setback caused a 58 percent drop in Momenta's stock. (See BioWorld Today, Nov. 7, 2007.)

More recently, Momenta reported that the agency has requested additional data to support the ANDA but has not yet asked for human clinical trials.

Wheeler said Momenta learned important lessons from its experience with generic Lovenox, specifically how to "work with the agency on a complex application" and think "proactively" about issues such as immunogenicity.