Old Drugs, New Tricks: Repurposing Through 505(b)(2) Submissions

Summer Associates Hannah Jankunis and Matthew Swazer also contributed to this article. 

FDA DRUG APPROVAL PATHWAYS

505(b)(1) New Drug Application
De novo drug development is costly and time consuming. Some studies estimate that research and development costs for a 505(b)(1)¹ New Drug Application (NDA) range from $314 million to $4.46 billion.² Additionally, the time between drug development and launch generally takes about twelve years.³ Whereas an approved NDA is required to market that drug in the United States, granted U.S. patents are needed to protect that market from copycats, by preventing competitors from making, using, selling, offering to sell, or importing a patented drug in the United States for a limited period.⁴ Thus, drug developers must separately apply for both drug approval from the Food and Drug Administration (FDA) and patent protection from the United States Patent and Trademark Office (USPTO)⁵ to market and protect their new drugs.

The 505(b)(1) pathway is the most expensive, but also provides the opportunity to earn the most extensive patent and non-patent marketing exclusivities. NDAs under 505(b)(1) require the sponsor to conduct de novo preclinical and clinical studies firmly establishing the safety and efficacy of their proposed new drugs.

Once an NDA is approved, subsequent or “follow on” 505(b)(2) and 505(j) applications have the option to designate that new drug as a “reference listed drug” (RLD) to rely on the extensive safety and efficacy data to support their own approvals, thus bypassing the high costs for conducting their own studies. Of course, the benefits of bypassing those costs also come with various obligations on the subsequent applicants that take advantage of piggy backing on the RLD. For example, the FDA’s online database Approved Drug Products with Therapeutic Equivalence Evaluations, colloquially known as the “Orange Book,” publishes a list of all approved drugs and lists every patent that covers each drug.⁶ Any subsequent applicant who designates another drug as its RLD must certify to any patents covering that RLD, and will be subject to potential delays, from either litigation or marketing exclusivities before receiving approval of their own drugs.

505(j) Abbreviated New Drug Application

Drug developers seeking to introduce low-cost generic versions of branded drugs need only submit an Abbreviated-NDA (ANDA) referencing its branded counterpart as the RLD under 505(j). An ANDA is substantially less expensive than an NDA because it is a duplicate of an approved new drug.⁷ As a “duplicate,” the ANDA does not have to demonstrate independent safety and efficacy of the proposed generic drug, but rather simply has to show that it is “bioequivalent”⁸ to the corresponding branded RLD.⁹ But a generic under the ANDA pathway must meet the FDA’s strict “sameness” requirement that the proposed generic must be identical to the RLD with respect to active ingredient, salt form, dosage strength, dosage form, route of administration, labeling, and intended use. Consequently, there is limited opportunity to design around a brand drug’s patents or make product modifications.

To incentivize early generic competition, Congress provided for certain economic rewards for being the first company to file an ANDA that challenges one or more Orange Book listed patents, and seeks to enter the market prior to patent expiration. This challenge is known in the industry as a “Paragraph IV certification.”¹⁰ Successful challengers are awarded 180 days of generic market exclusivity.¹¹

Click the link below to read the full article.