By Sherri Oslick --
In a Breakout Session held last Wednesday at BIO 2009, a panel consisting of David Bassett, a Partner at WilmerHale; Genia Long, Managing Principal at Analysis Group; David Ridley, Assistant Professor of Business Administration at the Fuqua School of Business at Duke University; David Korn, Sr. Assistant General Counsel for the Pharmaceutical Researchers and manufacturers of America (PhRMA); and DR. Maggie Shafmater, Senior Vice President and Chief Patent Counsel for Genzyme Corp., presented a session entitled: "Shaping Follow-on Biologics Policy: The Interplay of Data Exclusivity, Patient Safety and Patents."
While the session did not reveal much in the way of new information or insights to those familiar with follow-on biologics legislation and its surrounding issues, it did provide a comprehensive and well-organized summary of the state of follow-on biologics policy, including the current state of follow-on legislation and the special challenges presented by biosimilars.
The session began with a discussion by Mr. Bassett of the current situation with biologics, which were noted to make up a rapidly growing area, to have provided breakthrough treatments in cancer and other diseases, and to possess unique scientific characteristics that make the challenge of bringing them to market more significant than small molecule drugs. Currently, however, there is no regulatory pathway for follow-on biologics. The key questions regarding follow-on policy were stated to be: What clinical and other evidence is needed to establish similarity? What exclusivity is to be given to the innovator? What should the standard of interchangeability be? How should economic incentives for continuing innovation be set -- in other words, how should the need for innovation be balanced with the need for lower cost drugs?
Addressing the fundamental differences between biologics and small molecule drugs, Mr. Korn noted that all the issues surrounding follow-on policy proceed from the fact that unlike small molecule drugs, follow-on biologics are similar to, but not the same as, the innovator drug. Relative to small molecule drugs, biologics are different in composition, size, and structure, and have special manufacturing concerns (e.g., are more sensitive to temperature and shear forces) and clinical safety testing concerns (e.g., species specificity may limit the standard pre-clinical models typically used for safety testing). For these reasons, different scientific and regulatory standards should be used for their approval -- due to molecular similarity rather than identity, clinical trials are a must as are different names, for example.
Mr. Ridley addressed the issues of patient safety and efficacy, noting that concerns in this area center on having a clear regulatory pathway in place for new product categories distinct from small molecules, including a system for distinct labeling and naming, and adequate quality standards of pre-clinical and clinical testing requirements. To the latter concern, it was noted that the scope of pre-clinical and clinical requirements for safety and efficacy would necessarily include some case-by-case elements. Appropriate risk management plans and active pharmacovigilance are also key elements of the regulatory pathway.
Addressing the issue of data exclusivity, and the need to balance long-run innovation incentives with short-term cost savings from price competition, Ms. Long initiated the discussion by noting that patent protection and data exclusivity provide complimentary incentives. Data exclusivity, noted Ms. Long, prevents "free riding" on the investments necessary to conduct clinical studies and provides protection where short remaining patent terms following approval may be an issue, as well against design-arounds (a particular issue with follow-ons). The key question, however, is what the length of the exclusivity period should be. According to Ms. Long, there are two ways to view the exclusivity time-frame: 1) the "break even" point of view in which the balance between innovation costs and exclusivity is just over even, which translates to a 12-16 year period; and 2) a timeframe comparable to what small molecules experience, which is roughly a 12 year period.
Patent protection, noted Dr. Shafmater, provides incentives for innovation by protecting investments in technological improvements (versus data exclusivity, which only protects against others relying on one's clinical trial data), but patent rights are often narrow (e.g., to a specific sequence with a limited range of homology, or having a host cell limitation) leaving room for design-arounds. And over time, patent rights become less and less certain as the requirements of patent law (e.g., novelty and non-obviousness) change. In short, legislation will need to recognize that follow-ons are different, including from a patent protection perspective.
The remaining formal part of the presentation focused on the two pending pieces of follow-on legislation: H.R. 1427, the Waxman Bill, and H.R. 1548, the Eshoo bill. The Waxman bill was introduced on March 11, 2009, the Eshoo bill six days later on March 17, 2009. Salient provisions of the Waxman bill include:
• Data Exclusivity: only for products approved after the bill passes; 5 year period for the first "major substance"; 3 years if the "major substance" was previously approved and the product represents a significant therapeutic advance; 6 month extension for a significant therapeutic advance or a new patient population.
• Patent Provisions: innovator has no access to application for follow-on; follow-on applicant can request patent information from innovator at any time; failure of the innovator to timely identify patents in response to such a request results in forfeiture of the patent; failure of the innovator (or patent owner) to sue within 45 days of notice results in the inability to obtain an injunction against the follow-on applicant.
And of the Eshoo bill:
• Data Exclusivity: 12 year period; 2 year extension if a new indication is found within the first 8 years of licensure; 6 months additional for pediatric exclusivity; also includes an exclusivity period of 2 years for the follow-on applicant with an interchangeable biosimilar.
• Patent Provisions: only applies to patents expiring after the 12 year exclusivity period; the FDA will publish receipt of a follow-on application with 30 days with direct notice to the innovator; follow-on applicant will show application to innovator and the innovator will provide patent information; follow-on applicant can certify specific patents, which creates an artificial act of infringement, allowing courts to decide infringement issues before the follow-on goes to market; remedy in court is delayed approval of follow-on until after exclusivity period.
UPDATE: For those interested in obtaining a copy of the slides for the above presentation, they can be accessed here.
• "Third Follow-on Biologics Bill Introduced in 111th Congress," April 1, 2009
• "Second Follow-on Biologics Bill Is Introduced in House," March 18, 2009
• "Waxman Introduces Follow-on Biologics Bill," March 11, 2009
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