Last month, we reported that King Pharmaceuticals (KG) had filed a citizen petition that could delay final approval of numerous ANDAs for generic versions of Altace (ramipril), which were set to earn final approval on June 7. King's citizen petition asked FDA to require ANDA applicants for ramipril to file patent certifications with respect to newly-issued U.S. Patent No. 7,368,469, a method-of-use patent.
On June 18, FDA denied King's citizen petition, concluding that the ANDAs may be approved with section viii "carve out" statements and that patent certifications are not necessary. The same day, FDA granted final approval to the ANDAs.
FDA's letter decision explains that King sought for FDA to
confirm that label information describing cardiovascular outcomes from the Heart Outcomes Prevention Evaluation (OTC:HOPE) trial and the related indication may not be omitted from the labeling of any [ANDA or 505(b)(2) application] that relies upon an Altace product and seeks approval for treatment of hypertension. Accordingly, the Petition seeks to confirm that ANDAs and 505(b)(2) applications that reference an Altace product must contain an appropriate patent certification to [the '469 patent] and may not contain a statement pursuant to section 505(b)(2)(NYSE:B) or 505(j)(2)(NYSE:A)(viii) of the Act explaining that the patent does not claim a use for which the applicant is seeking approval.
FDA's letter concludes
that ANDA and 505(b)(2) applicants seeking approval of ramipril products can omit from the product labeling the information from Altace labeling related to a reduction in risk of myocardial infarction, stroke, and death from cardiovascular causes (the HOPE indication) without rendering the proposed drug product less safe or effective than Altace products for the remaining conditions of use (treatment of hypertension and use in heart failure post-myocardial infarction).
If FDA had reached the opposite conclusion and required ANDA applicants to include the HOPE indication in their labeling, the applicants would have had to file a paragraph III or IV certification to the '469 patent. Although a paragraph IV certification would not have led to a 30-month stay of FDA approval (because the ANDAs had already been filed when King submitted the patent for listing in the Orange Book), such a certification would have allowed King to sue the applicant under 35 USC 271(e)(2) for infringement of the '469 patent. Thus, the applicant would have had to decide whether to launch their generic ramipril product at-risk of liability for patent infringement.
The FDA's website shows that seven ramipril ANDAs were granted final approval immediately after FDA denied King's citizen petition and that Cobalt and Lupin also have final approval, for a total of nine generic ramipril products currently on the market.