Amarin Corp Plc (AMRN)

[HDGabor]

j-

Hmm so can list side effects with no mention anywhere on label of where that info came from eg reduce it?

Information under the Warnings and Precautions heading must include a concise summary of the most clinically significant safety concerns. (Labeling for Human Prescription Drug and Biological Products – Implementing the PLR Content and Format Requirements). Cross-reference and details (in this case cross-reference is mandatory) could be included (see: Vascepa) but I do not see it as mandatory (see: Crestor).

Now how is it that GsK was able to pull their htn patents and essentially left tevA with a full label including the chf indication but we can’t pull our marine and be left with reduce it only. I guess that’s the only remaining question.

(i) hypertension and post-MI LVD / 067 paten = MARINE
(ii) congestive heart failure (CHF) / 069 patent = REDUCE-IT
(ii) congestive heart failure (CHF) / 000 patents = new REDUCE-IT

The pull of the HTN (hypertension ’067” / MARINE) patent is irrelevant (was issued in 1985 and expired on March 5, 2007) pull of the 069 (R-IT) from and list 000 patent (new R-IT) matter.

- In March 2002, Teva applied for FDA approval of its generic carvedilol, certifying in the Abbreviated New Drug Application (“ANDA”) under Paragraph III of the HatchWaxman Act that its product would not be launched until the ’067 (MARINE) patent expired in March 2007. (aka generic V would not be launched until the MARINE patents are valid ... is not a case anymore).
- Teva also made a Paragraph IV certification that the ’069 (R-IT) patent was “invalid, unenforceable, or not infringed,” and, on May 24, 2002, Teva sent GSK a Paragraph IV notice stating that the claims of the ’069 (R-IT) patent are invalid for anticipation or obviousness. [Please note: Upon receiving the certifications, unlike the typical HatchWaxman case, GSK did not sue Teva based on any of the Orange-Book-listed patents. Instead, seemingly acknowledging the deficiencies in its patent, GSK filed a reissue application for the ’069 patent.]
- Before Teva’s carvedilol product was finally approved, Teva amended its ANDA and proposed label to carve out the CHF ("069" / R-IT) indication. Thus, in September 2007, when the FDA finally approved Teva’s ANDA as an AB-rated version of GSK’s Coreg®, Teva’s skinny label was only indicated for hypertension and post-MI LVD (MARINE) — neither of which was covered by any patent (MARINE patents are invalid).
- GSK on November 25, 2003 filed an application to reissue the ’069 (R-IT) patent. The ’000 (new R-IT) patent was issued on January 8, 2008.
- After the ’000 patent’s issuance in 2008, GSK quickly removed its original patent (069 / R-IT) from the Orange Book and listed the ’000 (new R-IT) patent. [Please note: GSK, however, did not assert the ’000 patent against any generic based on their ongoing sales of generic carvedilol under the approved skinny labels.]
- in 2011, the FDA directed Teva to revise its label to include the CHF (R-IT) indication. [Please note: it was triggered by the pull of the 069 (R-IT) patent however - no clue why - FDA / Teva ignored the listed 000 (new R-IT) patent.]

Inducement was determined based on:

(I) skinny label (w/o CHF ... MARINE only) period (January 8, 2008 / the date of the ’000 (new R-IT) patent’s issuance - to April 30, 2011 / the last day before Teva amended its label)
Circumstantial evidences, as
(a) Teva’s promotional materials referred to Teva’s carvedilol tablets as AB rated equivalents of the Coreg® tablets (catalog lists Teva’s carvedilol tablets next to Coreg® tablets and uses the phrase “AB rating,” and that this would lead a doctor to believe that “they’re therapeutically interchangeable.” ... the FDA’s “general position is that if you compare one product to another by name, you are implying the use of the product.”)
(b) There was ample record evidence of promotional materials, press releases, product catalogs, and testimony of witnesses from both sides

(II) full label (w CHF ... MARINE + R-IT) period (May 1, 2011 / the first day after Teva amended its label to June 7, 2015 / the date of expiration of the ’000 (new R-IT) patent)
(a) Circumstantial evidences (see above)
(b) the FDA label, including CHF (R-IT)

The big question (I have no idea) why the FDA ignored the 000 (new R-IT) patent when directed Teva to revise its label to include the CHF (R-IT) indication ... The FDA cannot approve a generic drug that would infringe a patent ... so why FDA ordered an infringement?

For Amarin / Vascepa (based on the case above):
- MARINE (067)patents (in the OB or pull from the OB) are irrelevant (until they are invalid ... and most likely they reamin invalid forever.)
- generics has to promote / marketing the R-IT usage (e.g. promotional materials, press releases, product catalogs) - meanwhile has MARINE only label - to commit inducement ... it is not likely [Please note: Presentation of existing market / existing revenue of Vascepa - the referenced slide - or the contracted / available quantity are not circumstantial evidences ... none of it encourage, promote the R-IT usage ... do not influence doctors’ prescribing decisions.]
OR
- the existing R-IT (069) patents should be pulled from the OB ... new R-IT (000) patents should be listed in the OB AND (!!!) FDA has to ignore the new, listed patent and should instruct the generics to include R-IT usage / indication ... meanwhile I do not know / see the reason why they did in the case above I do not think it is likely.

Sum: The Teva vs GSK case is "unique" as:
- Teva commit inducement by circumstantial evidences
- FDA / Teva ignored the OB listed patent, FDA / Teva included a patented Metod of Use (CHF / R-IT) in the label

Best,
G

ps.: PROST, Chief Judge, dissent is a BS ... He says Teva is not liable for inducement because they tried to "kill / shot down " (with Circumstantial evidences and label) Coreg they "were not on target" (Teva’s did not seem to influence doctors’ prescribing decisions). You do not have to kill somebody to be found guilty ... attempt is enough.