DALVANCE Gains Bonus Exclusivity; FDA Grants the First Period of GAIN Act Exclusivity

June 19, 2014

By Kurt R. Karst –     

After years of relative quiet, the Orange Book list of exclusivity terms has gotten quite a workout over the past year with the addition of several new terms to account for new non-patent marketing exclusivities.  First there was the addition of “NCE*” exclusivity, defined as “NEW CHEMICAL ENTITY (AN ENANTIOMER OF PREVIOUSLY APPROVED RACEMIC MIXTURE. SEE SECTION 505(U) OF THE FEDERAL FOOD AND DRUG COSMETIC ACT),” that FDA created after the approval of NDA No. 204168 for FETZIMA (levomilnacipran) Extended-release Capsules, 20 mg, 40 mg, 80 mg and 120 mg (see our previous post here).  Then there was the addition of “RTO*” and “RTO**” exclusivities, defined as “OTC USE FOR WOMEN AGES 15 AND 16” and “OTC USE FOR WOMEN 14 AND BELOW,” respectively, that FDA created to account for various supplemental approvals under NDA No. 021998 for PLAN B One-Step (levonorgestrel) Tablets, 1.5 mg (see our previous post here).  Now that FDA has approved the first drug product designated as a Qualified Infectious Disease Product (“QIDP”), the Agency has once again added to the Orange Book list of exclusivity terms.  The term “GAIN” was added to the Orange Book Cumulative Supplement last week in relation to NDA No. 021883 for DALVANCE (dalbavancin HCl) Lyophilized Powder for Injection, 500 mg.  FDA approved DALVANCE on May 23, 2014 in the treatment of acute bacterial skin and skin structure infections.  With a period of NCE exclusivity that expires on May 23, 2019, but that is extended under the Generating Antibiotic Incentives Now Act (“GAIN Act”) by an additional 5 years to May 23, 2024, the GAIN exclusivity FDA granted for DALVANCE is the latest expiring period of non-patent exclusivity ever listed in the Orange Book (not to mention the longest period of exclusivity that FDA has granted for a drug product in decades – see FDC Act § 505(j)(5)(F)(i)). 

The GAIN Act was enacted as Title VIII of the 2012 FDA Safety and Innovation Act (“FDASIA”) and is intended to encourage the development of antibacterial and antifungal drug products that treat pathogens that cause serious and life-threatening infections.  The GAIN Act builds on provisions included in the 2007 FDA Amendments Act intended to improve antibiotic access and innovation, and addresses
issues raised since the enactment of FDAAA (see here).  (Legislation currently pending in Congress – the Antibiotic Development to Advance Patient Treatment Act of 2013, or “ADAPT Act” – is viewed as successor legislation to the GAIN Act that would further promote antibiotic drug development and approval (see our previous post here)).  After holding a public meeting in December 2012, FDA proposed a list of qualifying pathogens in June 2013, and finalized that list earlier this month.  In addition to the exclusivity bonus, QIDP-designated products are also eligible for designation as a fast-track product and for priority review consideration.

With respect to marketing exclusivity, the GAIN Act amended the FDC Act to add Section 505E, which, among other things, grants an additional 5 years of marketing exclusivity upon the approval of an NDA for a drug product designated by FDA as a QIDP.  Thus, for a QIDP, the periods of 5-year NCE exclusivity (FDC Act §§ 505(c)(3)(E)(ii) and (j)(5)(F)(ii))), 3-year new clinical investigation exclusivity (FDC Act §§ 505(c)(3)(E)(iii)-(iv) and 505(j)(5)(F)(iii)-(iv)), and 7-year orphan drug exclusivity (FDC Act § 527) become 10 years, 8 years, and 12 years, respectively.  (Pediatric exclusivity granted pursuant to FDC Act § 505A would extend the various exclusivity periods by 6 months.)  In addition, for a QIDP with NCE exclusivity, the period during which an ANDA containing a Paragraph IV certification to an Orange Book-listed patent on the QIDP cannot be submitted is extended from 4 years after QIDP NDA approval to 9 years after approval.  Curiously, the GAIN Act does not specifically extend the 30-month stay period under FDC Act §§ 505(c)(3)(E)(ii) and (j)(5)(F)(ii)) from 7.5 years after NCE NDA approval to 12.5 years after QIDP NCE NDA approval.  In contrast, the statute's pediatric exclusivity provisions at FDC Act § 505A do specifically extend that period by 6 months.

There are some limitations on GAIN exclusivity.  The statute limits the exclusivity extension such that it does not apply to the approval of:

  1. a supplement to an application under [FDC Act § 505(b)] for any [QIDP] for which [a GAIN] extension . . . is in effect or has expired;
  2. a subsequent application filed with respect to a product approved under [FDC Act § 505] for a change that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device, or strength; or
  3. a product that does not meet the definition of a [QIDP] under [FDC Act § 505E(g)] based upon its approved uses.

The exclusivity record attained with the approval of DALVANCE might not last too long.  Future GAIN Act approvals are on the horizon (see here).  In addition, Congress is debating the creation of new and longer exclusivity periods (see here), such as under the Modernizing Our Drug & Diagnostics Evaluation and Regulatory Network Cures Act of 2013, or “MODDERN Cures Act of 2013” (see here and here).