Xifaxan® (rifaximin)
Case Name: Norwich Pharms., Inc. v. Kennedy Jr., Civ. No. 25-91, 2025 WL 1148463 (D.D.C. Apr. 18, 2025) (Howell, J.)
Drug Product and Patent(s)-in-Suit: Xifaxan® (rifaximin)
Nature of the Case and Issue(s) Presented: Salix holds NDAs for 200mg and 550mg Xifaxan. The 550mg strength product was approved to treat irritable bowel syndrome with diarrhea (“IBS-D indication”) and hepatic encephalopathy (“HE indication”). The Orange Book-listed patents cover Xifaxan’s use for HE, its uses for IBS-D, and others covered rifaximin polymorphs. On Dec. 18, 2015, Actavis submitted an ANDA for 550mg rifaximin tablets for both the IBS-D and HE indications that included Paragraph IV certifications as to the polymorph, IBS-D, and HE patents, including the ’573 HE patent. Actavis sued and the parties ultimately settled, permitting Actavis to enter the market no later than Jan. 1, 2028, over 22 months before the last of the Salix patents expires. During the Salix-Actavis litigation, FDA began reviewing Actavis’ ANDA, and after Salix had submitted a citizen petition, FDA revised draft product-specific guidance that required in vitro dissolution testing by Actavis under multiple physiologically relevant pH conditions and surfactant levels.
In December 2019, Norwich filed ANDA No. 214369 (“the ’369 ANDA”) for the 550mg strength, and ANDA No. 214370 (“the ’370 ANDA”) for 200mg strength. Norwich’s ’369 ANDA included Paragraph IV Certifications to the certain Orange-book listed polymorph, IBS-D, and HE patents. Norwich’s ’370 ANDA did not make any Paragraph IV Certifications. Salix sued in the District of Delaware asserting claims of patent infringement as to twenty-six patents, but in compliance with the scheduling order, Salix limited the number of challenged patents contested at trial to seven. After trial, the parties filed a joint stipulation asking the court to enter a final judgment of non-infringement regarding certain, but not all, claims, limited to Norwich’s ’369 ANDA” and “current ANDA product.” The district court determined that all of Salix’s patents were invalid, except for the HE indication ’573 patent, and entered a judgment order that “the effective date of any final approval by the [FDA] Norwich’s ANDA No. 214369 is to be a date not earlier than the date of the expiration of the last to expire” ’573 HE indication patent, which is October 2, 2029. Even after Norwich carved out the HE indication from its ’369 ANDA, thereby excising the only infringing indicated method of use, the Federal Circuit affirmed.
On June 2, 2023, the FDA granted tentative approval of Norwich’s ’369 ANDA. Norwich sued the FDA in the District of Columbia, pursuant to the APA, seeking final approval of the ’369 ANDA. The court held that “Norwich has failed to show that the law is so clear that the FDA should have stretched to read the Delaware District Court’s final judgment and Rule 60(b) decision in a manner that ignores their plain terms.” Norwich has appealed and that appeal remains pending.
Norwich then amended its ’370 ANDA on May 20, 2024, to add the 550mg dosage strength to treat IBS-D. Its amended ’370 ANDA contains both Paragraph IV certifications and section viii statements to various Salix patents, including the ’573 HE patent. This amendment has resulted in two separate litigations. First, because two additional IBS-D patents issued following the first Norwich district court litigation, given the new paragraph IV certifications to those patents, Salix filed another patent litigation suit, this time in the District of New Jersey. Second, Norwich sought final approval of its amended ANDA given the HE carve out and the fact that Actavis has forfeited its 180-day exclusivity for failure to market and/or failure to obtain tentative approval. On Jan. 8, 2025, FDA issued a memorandum disagreeing with Norwich’s position. Norwich brought this action to overturn FDA’s denial of final approval. Norwich moved for a preliminary injunction, and at the parties’ request, Norwich’s motion was consolidated with the merits and treated as cross motions for summary judgment. The court denied Norwich’s motion for summary judgment and granted FDA and intervenor defendants’ cross-motions for summary judgment.
Why FDA Prevailed: The court found that all tools of statutory interpretation led to the conclusion that FDA’s decision of granting Norwich’s ’370 ANDA tentative approval—and not final approval—because Actavis has not forfeited its exclusivity rights is not contrary to law. The parties do not dispute that Actavis was the first filer and possessed 180-day exclusivity at the time it submitted its ANDA. The issue was whether it forfeited that right for failing to market its ANDA product or failure to gain tentative approval.
Failure to market. The statute states that the 180-day exclusivity period shall be forfeited by a first applicant if “[t]he first applicant fails to market the drug by the later of” with respect to the first applicant ..., the date that is 75 days after the date as of which, as to each of the patents with respect to which the first applicant submitted and lawfully maintained a certification qualifying the first applicant for the 180-day exclusivity period under subparagraph (B)(iv) … [i]n an infringement action or declaratory judgment action ..., a court signs a settlement order or consent decree that enters a final judgment that includes a finding that the patent is invalid or not infringed.” Norwich argued that the statute requires “matching” patent paragraph IV certifications between a first applicant’s ANDA and a subsequent applicant’s ANDA to prevent a first applicant from forfeiting its 180-day exclusivity. And because submitted a section viii statement, and not a Paragraph IV Certification, for the ’573 patent—i.e. Actavis and Norwich did not submit matching paragraph IV certifications for the ’573 patent—Actavis has forfeited its 180-day exclusivity to market 550mg tablets of rifaximin for IBS-D and HE, for which Actavis lawfully maintains a paragraph IV certification to the ’573 HE indication patent. In FDA’s view, forfeiture only concerns the “first applicant’s” paragraph IV certifications, and Norwich’s actions, whether a paragraph IV certification or a carve out, are of no moment. To trigger forfeiture, the statute requires a “forfeiture event” as to “each of the patents” the first applicant submitted and lawfully maintains. A “first applicant,” is an applicant that (1) “submits a substantially complete application” (2) “that contains and lawfully maintain[s] a [Paragraph IV Certification] for the drug” (3) “on the first day” that such an application is filed. Therefore, no forfeiture for failure to market has happened because all of the paragraph IV certifications Actavis has made with respect to listed Orange Book patents covering 550mg tablets of rifaximin qualify it for the 180-day exclusivity. Consequently, for 550mg tablets of rifaximin (the drug), Actavis’ paragraph IV certification for the ’573 HE patent qualified it as a first applicant, which has not been subject to a forfeiture event. Moreover, Norwich’s insistence that consideration of a subsequent applicant’s certifications is necessary ignores the fact that forfeiture events can occur without any subsequent applicant asserting paragraph IV certifications. “Accordingly, the presence of a discrete 180-day exclusivity period reinforces that only a first applicant’s Paragraph IV Certifications are material in determining forfeiture because the 180-day exclusivity period forecloses indefinite exclusivity periods based only on “matching” patent certifications between a first applicant and subsequent applicant’s applications.” Norwich’s read of the statute would have been correct prior to the MMA amendments to the Hatch-Waxman Act. Finally, “[r]eliance on a pre-MMA statute in a post-MMA world is a giant cautionary red flag as to the fundamental flaw in Norwich’s position(s) in this lawsuit.” Norwich’s approach was the law prior to those amendments, but that is no longer the case.
Failure to obtain approval. According to the relevant statute, a first applicant may forfeit its exclusivity by failing to “obtain tentative approval of the application within 30 months after the date on which the application is filed, unless the failure is caused by a change in or a review of the requirements for approval of the application imposed after the date on which the application is filed.” It is not in dispute that Actavis failed to obtain tentative approval of its ANDA within 30 months after filing its ANDA. The parties disputed, first, whether this statutory text either tolls or sets aside the 30-month deadline for obtaining tentative approval, and, second, whether the phrase “caused by,” in this statutory text demands “but-for” causation. On the first issue, the court rejected Norwich’s argument that the 30-month timeline is tolled because: (i) it finds no grounding in the text; (ii) Congress’ decision to omit such language was intentional by virtue of it including “tolling” and “extending” language in other sections of the statute; and (iii) no guidance exists as to the calculation of a tolling period were one to exist. On the second issue, the court rejected Norwich’s but-for causation argument based, again, on the reading of the statute’s text. The “caused by” requirement in the statute is satisfied as long as a change in or review of the requirements for approval of an ANDA imposed after the application was filed is one of the causes of failure to get tentative approval.
The court further rejected Norwich’s reliance on textbook tort and criminal law examples for defining “cause.” “Norwich relies on tort and criminal law cases that do not interpret the relevant phrase ‘caused by’ but instead interpret ‘because’ and ‘results from.’ … [T]he flaw in Norwich’s position is that ‘[t]he judicial task when interpreting statutory language ... is to discern how Congress used ... word[s] in the law.’”
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