The FDA recently posted new guidance on its website awarding certain fixed-combination drug products (fixed-combinations) 5-year new chemical entity (NCE) exclusivity. While the Agency held previously that these products were ineligible for NCE exclusivity (5 years) if one component is already approved, with this new Guidance in effect, a drug product will be eligible for NCE exclusivity if the active moiety of one of its components was never before approved in the United States. The FDA rationale for this change is a way to incentivize the development of certain fixed-combination products particularly for therapeutic areas such as cancer, cardiovascular and infectious disease where fixed-combinations have become increasingly prevalent. In the nearly 20 years since FDA finalized the regulations on exclusivity, the Agency has approved 19 NDAs for fixed-combinations containing at least one new active moiety. More than half of these NDAs have gained approval within the last 7 years.

Key to this new guidance is the “timing” as the new exclusivity period applies from the date of the new guidance’s publication (October 2014). Meaning it won’t be retroactive, thereby being of no benefit to the petitioners who in 2013 petitioned the Agency to revise its current interpretation of the 5-year NCE exclusivity provisions with respect to fixed-combinations and submitted Reconsideration Petitions in 2014 after the original petitions were denied.

In 2013, Gilead originally petitioned FDA to recognize 5-year NCE exclusivity for Stribild (NDA 203100) (FDA-2013-P-0058), because Stribild is a fixed-combination that contains cobicistat and elvitegravir, both of which were previously unapproved active moieties at the time of Stribild’s approval. Stribild also contains two previously approved active moieties (emtricitabine; tenofovir disoproxil fumarate). After Gilead’s petition was filed, Ferring put forth a similar contention for its fixed-combination Prepopik (NDA 202535) (FDA-2013-P-0119), containing picosulfate, which was a new active moiety at the time of approval. Prepopik also contains two previously approved active moieties (citric acid; magnesium oxide). Bayer HealthCare Pharmaceuticals, submitted a citizen petition dated April 19, 2013, requesting 5-year NCE exclusivity for dienogest, the new active moiety in the fixed-combination Natazia (estradiol valerate; dienogest) (NDA 022252) (FDA-2013-P-0471), in spite of the fact that Natazia also contained a previously approved active moiety. Bayer has not filed a petition for reconsideration.

Based on information in these petitions as well as the increasing importance of fixed-combinations to treat serious disease and conditions, the Agency concluded that a new interpretation of 5-year NCE exclusivity for fixed-combination products would be beneficial to the public health leading to the new Exclusivity Guidance.

Unfortunately, as FDA will apply the new interpretation prospectively, these petitioners are not the ones who will benefit from this new ruling. As a result, simultaneous to denying the Reconsideration Petitions, the Agency issued the Exclusivity Guidance in final form.

Author:

Stacey Ayres, PhD
Director of Research Services