Washington Editor

WASHINGTON – After months of waiting for the first signs that the FDA is moving ahead with a regulatory pathway to approve follow-on biologics (FOBs), or biosimilars, a draft document obtained by Wall Street analysts over the weekend revealed that the agency plans to hold a two-day public meeting in November.

An FDA spokeswoman, however, declined to comment on whether the Nov. 2 and 3 dates outlined in the analyst-obtained document was indeed when the agency plans to hold the first in what is expected to be a series of public meetings to solicit comment from experts, innovators, patients and other stakeholders.

The Patient Protection and Affordable Care Act, signed into law by President Obama on March 23, gave the FDA the authority to create an abbreviated approval pathway for biologics that are demonstrated to be "highly similar" to or "interchangeable" with an FDA-approved innovator biologic. (See BioWorld Today, March 23, 2010.)

The biosimilars provision, known as the Biologics Price Competition and Innovation (BPCI) Act, provided 12 years of data exclusivity protection against FOBs products – a major win for the biotech innovator community.

The FDA last spring said it had formed an internal working group, known as the Biosimilar Implementation Committee, co-chaired by Center for Drug Research and Evaluation Director Janet Woodcock and Center for Biologics Evaluation and Research Acting Director Karen Midthun, to layout the agency's approach for ensuring the evaluation, review and approval processes would be achieved in a "consistent, efficient and scientifically sound manner."

John Jenkins, director of the Office of New Drugs, on May 17 appointed Leah Christl the newly created position of acting associate director for biosimilars within his office, where she was charged with overseeing the development of procedures and staff training for CDER's implementation of the FDA's new authority.

But since then, the FDA has remained mum about when it planned to issue guidelines and regulations under the biosimilars measure.

So analysts were eager to get their hands on the document, for which the FDA Monday said it had no comment.

According to the unofficial document, the agency is seeking input about the "scientific and technical factors related to a determination of biosimilarity or interchangeability; the type of information that may be used to support a determination of biosimilarity or interchangeability; development of a framework for optimal pharmacovigilance for biosimilar and interchangeable biological products; scope of the revised definition of a 'biological product'; priorities for guidance development; scientific and technical factors related to reference product exclusivity; scientific and technical factors that may inform the agency's interpretation of 'product class' as it relates to available regulatory pathways for certain protein products during the 10-year transition period following enactment of the BPCI Act; and the establishment of a user fee program for biosimilar and interchangeable biological products."

Because negotiations of new and reauthorized user fee programs historically have largely been conducted by trade associations representing the affected companies, the FDA also is seeking to identify "which existing industry trade associations represent such companies."

Deutsche Bank Equity Research analyst Robyn Karnauskas said the boundaries for biosimlars vs. interchangeables appeared to be the FDA's "key focus" for its public discussions.

She said she believed that the biologic "drift" was at the "forefront of the FDA's mind."

Many complex biologics have sugar chains that impact their efficacy and safety, and she noted that the FDA has made several statements over the years suggesting a primary concern that biosimilars have the same sugar structure for interchangeability and those sugar structures do not "drift," or change with time.

Indeed, such was highlighted by the FDA's decision to classify as a separate drug Genzyme Corp.'s Pompe disease drug Lumizyme, an enzyme that came from the same cell line as its Myzoyme (alglucosidase alfa). (See BioWorld Today, Oct. 22, 2008, March 4, 2009, March 13, 2009, and May 26, 2010.)

"Few companies have the ability to control for drift," Karnauskas said.

But with the long-awaited approval of its version of enoxaparin in July, Momenta Pharmaceuticals Inc. "may be the first," she declared. (See BioWorld Today, July 26, 2010.)

Momenta's drug is similar to Sanofi-Aventis Group SA's Lovenox (enoxaparin sodium), a complex protein-based anticoagulant derived from the blood thinner heparin.

"Momenta is one of a few that likely has the ability to reverse engineer biologics that have the same sugar pattern and has the know-how to implement process controls in place, which can control for 'drift,'" Karnauskas said.

Sanofi in July said it had "reservations" about Momenta's approval, since the new version had "not been subjected to extensive clinical trials to demonstrate its efficacy and safety" as Lovenox. Karnauskas said that while biosimilars and interchangeables may not be far off, "we think there will be few successful entrants."

And although the emergence of biosimilars will be of increasing concern in large-cap biotech, such as Amgen Inc. and Biogen Idec Inc., "we believe the hurdle for approval and interchangeability will be high. We also believe there are few companies with the know-how to gain approval."