The Office of Generic Drugs (OGD) updated its Paragraph IV Database (PIVDB) yesterday and two new entries caught my eye. For those of you not familiar with the PIVDB, it was developed to give prospective ANDA applicants information on when the first ANDA for a patent-protected product was submitted to OGD. This had two purposes: 1) It gave prospective ANDA applicants an indication that someone else had already submitted an ANDA for a particular product which may dissuade subsequent applicants from seeking to file an ANDA to challenge a patent if their sole goal was to be first to file.; 2) It gave the date of submission of the first applicant, and thus, the date of the first to file application(s), and firms would know from that date if they were eligible for award of 180-day exclusivity. The FDA does not provide the name of the applicant, only the date of submission, and thus, there could be either single or multiple applications submitted on that day.
Anyway, now back to the interesting listings. An ANDA for glycerol phenylbutyrate oral solution (a copy of the NDA for Ravicti held by Hyperion Therapeutics) was listed as submitted on November 19, 2013 and posted on 3/10/14 or about 4 months after the original submission. In this case, it is not the length of time the ANDA has been at OGD, but rather the exclusivity and patent issues associated with the product and the jump on first-to-file status that at least one generic firm has decided to seek, especially since the original NDA was approved on February 1, 2013, only 9 months prior to ANDA submission.
Ravicti is a new salt/ester of sodium phenylbuterate, the active ingredient in Buphenyl powder and tablets. Because it was a new salt or ester, it was awarded a period of 3-year Hatch-Waxman exclusivity for this change. In addition, because it serves an orphan population and it is a new entity, it was also awarded 7-year Orphan Drug Exclusivity (ODE) that expires February 1, 2020. Ravicti appears to have a single indication, and thus, it would seem that no ANDA can be approved until that ODE expires. There are also patents that cover the NDA product. A drug substance patent expires on February 7, 2015 and that patent also claims a use; however, there are two additional patents expiring in September 2030 and March 2032 that also include a use that would appear to block generic entry unless invalidated. If there is a little viii carve out potential (excluding a patent or exclusivity protected indication or information if there are other non-protected indications already approved) , it is not obvious from the use codes and the labeling related to the approved use of the product. In that regard, the ANDA applicant must either have something up its sleeve or is just worried about the median time to approval of an ANDA, since it would seem that the earliest that an ANDA could be approved, even if the patents are invalidated, with be about 6 years from now.
The second listing that got my blood flowing was for Memantine Hydrochloride extended-release capsules, a generic form of Namenda XR Capsules. There was an approximate 10-month period from submission to acceptance of the ANDA. While that is not the longest review time for completeness and acceptability we have seen, it certainly indicates that either OGD had a difficult time evaluating the ANDA for receipt (maybe bioequivalence issues?) or their backlog could be a factor.
OGD publishes new additions to the list frequently, and often times, there are more there than meets the eye. You may want to zero in on one of the updates if this sort of thing interests you and your firm.
