New Legislation Would Provide Exclusivity Add-on for Significant Drug Combinations

October 2, 2012

By Kurt R. Karst –      

Legislation co-sponsored by Representatives Brian Bilbray (R-CA), Carolyn Maloney (D-NY) and Rosa DeLauro (D-CT), and supported by the Melanoma Research Foundation, seeks to encourge the development of so-called “significant drug combinations” by offering the carrot of an extension of marketing exclusivity. 

H.R. 6502, the “Life-Threatening Diseases Compassion through Combination Therapy Act of 2012,” was recently introduced and appears to be modeled after the Generating Antibiotic Incentives Now Act (“GAIN Act”), which was enacted under Title VIII of the FDA Safety and Innovation Act (“FDASIA”) (see here).  The GAIN Act, which is intended to encourage the development of antibacterial and antifungal drug products that treat pathogens that cause serious and life-threatening infections, amended the FDC Act to add Section 505E to, among other things, grant an additional 5 years of marketing exclusivity upon the approval of an NDA for a drug product designated by FDA as a Qualified Infectious Disease Product.  (FDA recently granted the first GAIN Act designation – see here – and there have already been winners and losers as a result of the new law – see here.)  Similarly, H.R. 6502 would amend the FDC Act – also to add Section 505E (and therefore, either an error/oversight, or perhaps an indication that the bill was in the works prior to the enactment of FDASIA) – to add 6-months of marketing exclusivity to 5-year new chemical entity exclusivity, 3-year new clinical investigation exclusivity, “or” 7-year orphan drug exclusivity for a drug product approved under an NDA and that contains a “significant drug combination” designated as such by FDA.  The bill also provides for priority (6-month) review of an NDA for a drug product containing a designated “significant drug combination.”

The bill defines a “significant drug combination” to mean a combination of two or more drugs, which can include a biologic subject to licensure under PHS Act § 351, that:

(1) when used in combination, offer the potential to significantly advance treatment for a serious or life-threatening disease;

(2) in combination, meet the criteria for codevelopment of drug combinations, as specified in the [FDA’s] guidance document entitled “Guidance for Industry: Codevelopment of Two or More Unmarketed Investigational Drugs for Use in Combination” or a successor document; and

(3) includes at least 2 drugs that are not approved under [FDC Act § 505] or licensed under [PHS Act § 351].

To qualify for the exclusivity extension under H.R. 6502, the sponsor of an NDA for a drug product containing at least two new drugs (and/or biologics) must, prior to the approval of the NDA, seek and obtain FDA designation of a drug combination as a “significant drug combination.”  In making “significant drug combination” designations FDA would be required to take into account the recommendations of a task force that would be created by the bill.  Among other things, the task force would be required to develop a list of types of drug combinations that should be designated  as “significant drug combinations.”  

The exclusivity extension under H.R. 6502 does have some limitations.  And they are reminiscent of the exclusivity limitations included in the GAIN Act and in the Biologics Price Competition and Innovation Act of 2009.  Specifically, the exclusivity extension does not apply to certain NDA supplements if an extension was previously granted, and for a subsequent NDA submitted “by the same sponsor or manufacturer of a drug in a designated significant drug combination. . . (or a licensor, predecessor in interest, or other related entity)” for certain changes, such as a new indication, or for “a modification to the structure of the drug that does not result in a change in safety or effectiveness.”