Case 1:22-cv-02159 Document 1 Filed 07/21/22 Page 1 of 27
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF COLUMBIA
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`AVADEL CNS PHARMACEUTICALS, LLC
`16640 Chesterfield Grove Road, Suite 200
`Chesterfield, MO 63005
`
`Plaintiff,
`
` v.
`
`XAVIER BECERRA, Secretary of Health and
`Human Services
`200 Independence Avenue, SW
`Washington, DC 20201;
`
`U.S. DEPARTMENT OF HEALTH AND
`HUMAN SERVICES
`200 Independence Avenue, SW
`Washington, DC 20201;
`
`ROBERT M. CALIFF, Commissioner of Food
`and Drugs
`10903 New Hampshire Avenue
`Silver Spring, MD 20993; and
`
`U.S. FOOD AND DRUG
`ADMINISTRATION
`10903 New Hampshire Avenue
`Silver Spring, MD 20993,
`
`Defendants.
`
`1:22-cv-2159
`Case No. _____________
`
`REDACTED
`
`COMPLAINT FOR DECLARATORY AND INJUNCTIVE RELIEF
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`Plaintiff Avadel CNS Pharmaceuticals, LLC (“Avadel”) brings this suit against Defendants
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`Xavier Becerra, in his official capacity as Secretary of Health and Human Services; the U.S.
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`Department of Health and Human Services (“HHS”); Robert Califf, in his official capacity as
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`Commissioner of Food and Drugs; and the U.S. Food and Drug Administration (“FDA”), and
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`alleges as follows:
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`PRELIMINARY STATEMENT
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`1.
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`Narcolepsy is a rare but serious chronic neurological disorder that affects the
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`brain’s ability to control sleep-wake cycles. People suffering from narcolepsy experience
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`excessive daytime sleepiness and may experience uncontrollable episodes of falling asleep during
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`the daytime. It is estimated that less than 200,000 Americans suffer from narcolepsy.
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`2.
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`Although there is no cure for narcolepsy, certain types of medicine can treat some
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`of its symptoms. One such drug is gamma-hydroxybutryate (“oxybate”), a central nervous system
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`depressant that helps to induce deep, restful sleep.
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`3.
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`Since 2002, oxybate has been marketed in the United States exclusively by Jazz
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`Pharmaceuticals plc (“Jazz”) under the brand name Xyrem, and, since 2020, Xywav. But a critical
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`problem with Jazz’s oxybate products is that they are immediate release formulations requiring
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`two doses—one right before bedtime, and a second dose between two-and-a-half to four hours
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`later—which necessitates people already suffering from a sleep disorder to set an alarm to
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`forcefully awaken in the middle of the night to take the second dose.
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`4.
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`Avadel is a biopharmaceutical company focused on researching and developing
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`drugs to treat narcolepsy. For almost a decade, Avadel’s focus has been on the development of
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`LUMRYZ™, an innovative product that uses proprietary technology designed to enable dosing
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`once before bedtime of sodium oxybate (a type of oxybate). That once before bedtime dosing
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`regimen allows for improved patient safety, compliance, and quality of life by enabling patients to
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`avoid setting an alarm to awaken in the middle of the night to take a second dose, thus offering the
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`possibility of an uninterrupted night of restorative sleep.
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`5.
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`To provide these benefits to patients, on December 15, 2020 Avadel submitted a
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`new drug application (“NDA”) for LUMRYZ to the U.S. Food and Drug Administration (“FDA”
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`or the “Agency”) pursuant to Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act
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`2
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`(“FDCA”), which provides streamlined pathways for approval of drugs that are based on the same
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`active ingredient as—but which are not identical to—a previously approved drug.
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`6.
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`To facilitate notice to owners of previously approved drugs that their intellectual
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`property rights might be impacted by such an NDA, a Section 505(b)(2) applicant must file a
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`“patent certification” or a “patent statement” regarding certain patents that relate to the previously
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`approved drug. 21 U.S.C. §§ 355(b)(2)(A), (b)(2)(B).
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`7.
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`Patent certifications are filed when an existing patent implicates the new drug, and
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`filing a certification can cause mandatory delays in FDA’s approval of the new drug; patent
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`statements, by contrast, are filed when a patent does not implicate the new drug, and cause no
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`approval delays. FDA instructs applicants to make this determination by reviewing FDA’s
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`“Orange Book,” an FDA database that publishes certain summary information about patents
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`associated with approved drugs.
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`8.
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`With its NDA, Avadel submitted to FDA required information about potential
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`overlap between the LUMRYZ NDA and patents held by Jazz. Jazz distributes Xyrem and Xywav
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`pursuant to an FDA-mandated Risk Evaluation and Mitigation Strategy (“REMS”), which was
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`designed by Jazz such that distribution occurs through a single, centralized pharmacy and database,
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`to prevent misuse and diversion of oxybate—which has potential for abuse. Jazz also holds a
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`patent that it alleges pertains to its single, centralized REMS drug distribution database, U.S. Patent
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`No. 8,731,963 (the “Jazz REMS patent” or “’963 patent”), which it has filed under “use code” U-
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`1110 in FDA’s Orange Book.
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`9.
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`LUMRYZ will also be distributed under a REMS, but Avadel has developed its
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`own REMS system and will not use Jazz’s. The LUMRYZ NDA accordingly included a “patent
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`statement” affirming that the Jazz REMS patent, as described by Jazz’s use code U-1110, does not
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`3
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`“claim[ ] a use for such drug for which the applicant is seeking approval,” because Jazz’s
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`description of that patent in its use code U-1110 does not overlap with the LUMRYZ NDA. See
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`21 U.S.C. § 355(b)(2)(A).
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`10.
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`525 days after Avadel filed its NDA—and 221 days after FDA was required by law
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`to render its final decision on the NDA—FDA instead rendered a final decision on only one
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`discrete subcomponent of the LUMRYZ NDA, Avadel’s patent statement to the ’963 patent.
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`11.
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`In a 16-page decision that “constitutes a final decision on the appropriateness of
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`Avadel’s section 505(b)(2)(B) [patent] statement” (the “Patent Decision”), FDA concluded that
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`Jazz’s use code U-1110 does describe a patent that “claims a use for such drug for which the
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`applicant is seeking approval” through the LUMRYZ NDA, and ordered Avadel to “provide an
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`appropriate patent certification under 21 CFR 314.50(i)(1)(i)” certifying to an overlap between the
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`Jazz REMS patent, as described in Jazz’s use code, and the LUMRYZ NDA.
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`12.
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`FDA reasoned that because Jazz’s use code describes the use of “a computer
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`database in a computer system for distribution,” and because the proposed LUMRYZ REMS will
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`use four computer databases for distribution, Avadel must submit a patent certification certifying
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`to the alleged overlap between the two.
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`13.
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`The Jazz REMS patent does not expire until December 17, 2022, and Jazz has
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`asserted an additional six months of “pediatric exclusivity” with respect to the ’963 patent under
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`21 U.S.C. § 355a(b)(1)(B)(i)(II), until June 17, 2023. Accordingly, FDA’s Patent Decision meant
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`that the LUMRYZ NDA could not be approved immediately, at the soonest by July 22, 2022
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`(within 45 days of Avadel’s relevant patent certification submissions), and potentially not until
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`June 17, 2023, if Jazz were to sue Avadel for alleged infringement on the Jazz REMS patent as a
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`result of FDA’s mandated certification. See 21 U.S.C. § 355(c)(3)(C).
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`4
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`14.
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`In response to FDA’s Patent Decision, Avadel filed the FDA-ordered “patent
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`certification” under protest on June 6, 2022, explaining its continued disagreement with FDA’s
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`decision that Jazz’s use code describes a patent that “claims a use for such drug for which the
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`applicant is seeking approval.” Id. § 355(b)(2)(A).
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`15.
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`On July 18, 2022, FDA issued a tentative approval of the LUMRYZ NDA (the
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`“Tentative Approval”). A tentative approval is not a full, final, or effective approval of an NDA.
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`Rather, a tentative approval provides that an NDA is approvable, provided that a future
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`contingency is met that would permit the NDA to obtain final approval at a later time.
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`16.
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`FDA’s Tentative Approval explained that the final approval of the LUMRYZ NDA
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`would be “made effective immediately, unless an action is brought for infringement of one or more
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`of the patents that were the subject of a paragraph IV certification” by July 22, 2022. FDA further
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`clarified that “[i]f such a patent infringement action is brought prior to the expiration of 45 days .
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`. . your application would be subject to a 30-month stay of approval . . . .”
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`17.
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`On July 15, 2022, Jazz filed a lawsuit against Avadel for alleged infringement of
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`the ‘963 patent in the United States District Court for the District of Delaware, case number 1:22-
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`cv-00941-UNA. Due to FDA’s Patent Decision and the resultant patent certification to the ‘963
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`patent under protest, this lawsuit triggered the stay identified by FDA.
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`18.
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`That stay now precludes the immediate approval of the LUMRYZ NDA, as would
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`have otherwise been possible in July 2022, until expiration of the ‘963 patent term and the related
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`term of pediatric exclusivity in June 2023 (unless the stay is terminated earlier by, for example,
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`delisting of the ’963 patent from the Orange Book).
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`19.
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`FDA’s erroneous Patent Decision—coupled with Jazz’s lawsuit—has caused and
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`will continue to cause Avadel significant and irreparable harm. Avadel’s business is solely
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`5
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`Case 1:22-cv-02159 Document1 Filed 07/21/22 Page 6 of 27
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`dependent on the successful commercialization of LUMY7iii
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`21.
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`FDAerred under the Administrative Procedure Act (“APA”) in requiring Avadel
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`to submit a patent certification, for four independent reasons, any one of which would require
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`setting aside FDA’s Patent Decision.
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`22.
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`As an initial matter, under the plain statutory text, FDA lacks authority to second-
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`guess an NDA applicant’s decision concerning the type of patent certification or statement to
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`submit.
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`23.
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`In addition, even if FDA did have some role in second-guessing applicants’
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`decisions to submit patent statements or certifications, no certification was warranted here because
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`Jazz’s description of the Jazz REMSpatentin its use code U-1110 does not claim a “use” for any
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`“drug,” much less a use for sodium oxybate, as required by 21 U.S.C. § 355(b)(2)(A).
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`24.
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`Next, the patent description in Jazz’s use code, describing a computerized system
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`for drug distribution, does not “claim[ ] a use for such drug for which the applicant is seeking
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`approval,” id., for the additional reason that Avadel’s labeling does not mention any computer
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`system atall, as required by 21 C.F.R. § 314.50(i)(1)(11)(A)-(B).
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`25.
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`Andfinally, even if FDA could look beyond Avadel’s proposed labeling, Jazz’s use
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`codestill does not “claim[ ] a use for such drug for which the applicant is seeking approval,” 21
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`U.S.C. § 355(b)(2)(A), because the LUMRYZ REMS calls for the use of four separate and distinct
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`computer databases for distribution of LUMRYZ, rather than the single, centralized computer
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`system described by Jazz’s use code.
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`26.
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`For all of these reasons, FDA’s Patent Decision ordering Avadel to submit a patent
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`certification to the ’963 patent was arbitrary, capricious, contrary to law, in excess of statutory
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`jurisdiction and authority, and short of statutory right, and must therefore be set aside. See 5 U.S.C.
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`§ 706.
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`27.
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`But that alone will not remedy Avadel’s harms. FDA was required by statute to
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`either finally approve or set a hearing on the approvability of LUMRYZ within 180 days after the
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`filing date, or a later time agreed to between FDA and Avadel—in this case, October 15, 2021.
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`28.
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`Yet, more than 580 days have passed since the LUMRYZ NDA was filed, and it is
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`now over 278 days past FDA’s October 15, 2021 statutory deadline to render its final approval
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`decision on the NDA. That is agency action unlawfully withheld under the APA. See 5 U.S.C.
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`§ 706(1). FDA has never suggested that there is any remaining obstacle to NDA approval, apart
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`from this patent certification. Just the opposite: FDA expressly told Avadel that its NDA would
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`be subject to approval “immediately,” but for its Patent Certification decision (in combination with
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`the lawsuit filed by Jazz as a result of the Patent Certification decision).
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`29.
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`In light of Defendants’ ongoing violation of law and unlawful refusal to act on this
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`NDA as required by the FDCA, Defendants should be ordered to take final action on the LUMRYZ
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`NDA within 14 days of the Court’s order.
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`30.
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`Here, the issues raised by FDA’s Patent Decision are legal in nature and Avadel
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`satisfies all the requirement for expedited relief. Avadel respectfully requests preliminary
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`injunctive relief adjudicated on an expedited basis in consolidation with the merits.
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`7
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`PARTIES
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`31.
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`Avadel is the owner of NDA No. 214755 for LUMRYZ. Avadel is a Delaware
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`limited liability company with its principal United States place of business at 16640 Chesterfield
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`Grove Road, Suite 200, Chesterfield, MO 63005.
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`32.
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`Xavier Becerra is the Secretary of Health and Human Services and the head of
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`HHS. In this official capacity, Secretary Becerra has ultimate responsibility for activities at HHS,
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`including the actions complained of herein. He conducts his governmental activities at 200
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`Independence Avenue, S.W., Washington, D.C. 20201. His governmental activities also occur
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`nationwide.
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`33.
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`HHS is a department of the United States. Its headquarters and principal place of
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`business are at 200 Independence Avenue, S.W., Washington, D.C. 20201. Its governmental
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`activities occur nationwide.
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`34.
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`Robert Califf is the Commissioner of Food and Drugs and the head of FDA. His
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`governmental activities occur nationwide.
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`35.
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`FDA is an agency of the United States and a division of HHS. FDA’s headquarters
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`and principal place of business are at 10903 New Hampshire Avenue, Silver Spring, MD 20903.
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`Its governmental activities occur nationwide.
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`JURISDICTION, VENUE, EXHAUSTION, AND FINAL AGENCY ACTION
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`36.
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`This Court has jurisdiction pursuant to 28 U.S.C. § 1331. This action arises under
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`the Administrative Procedure Act (“APA”), 5 U.S.C. §§ 701-06. Avadel’s prayers for a
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`declaratory judgment and injunctive relief are authorized by the Declaratory Judgment Act, 28
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`U.S.C. §§ 2201 and 2202; the APA, 5 U.S.C. §§ 701-06; and 28 U.S.C. § 1361.
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`37.
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`Venue is proper in this District under 28 U.S.C. § 1391(e) because at least one
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`Defendant is an officer or agency of the United States and resides in this District.
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`38.
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`FDA explained in its Patent Decision that its Decision “constitutes a final decision
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`on the appropriateness of Avadel’s section 505(b)(2)(B) [patent] statement” submitted as part of
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`the LUMRYZ NDA. The Patent Decision is a final agency action reviewable under the APA. See
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`5 U.S.C. §§ 551, 704, 706; Purepac Pharm. Co. v. Thompson, 238 F. Supp. 2d 191, 202–03
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`(D.D.C. 2002), aff’d, 354 F.3d 877 (D.C. Cir. 2004).
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`39.
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`FDA’s failure to approve LUMRYZ within the statutorily mandated timeline for
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`review set forth in the FDCA, 21 U.S.C. § 355(c) also constitutes final agency action reviewable
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`under the APA as agency action unlawfully withheld. See 5 U.S.C. §§ 551, 704, 706; Sandoz, Inc.
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`v. Leavitt, 427 F. Supp. 2d 29, 34 (D.D.C. 2006).
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`40.
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`There is no statutorily mandated requirement that Avadel seek relief from the
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`Agency before bringing suit in this Court. Thus, administrative exhaustion is not a prerequisite to
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`suit.
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`41.
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`In any event, immediate judicial review is warranted for the very reason that Avadel
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`has already made exhaustive efforts to obtain relief from FDA to no avail.
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`42.
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`Specifically, Avadel has repeatedly requested FDA take action on the LUMRYZ
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`NDA consistent with governing law and has addressed all issues that FDA has raised regarding
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`LUMRYZ’s approvability. Despite these communications, FDA issued its Patent Decision
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`ordering Avadel to submit a certification to the ’963 patent and issued a tentative approval, but, to
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`date, has still failed to finally approve or offer a hearing on the approvability of the LUMRYZ
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`NDA. Avadel faces significant and irreparable harm from Defendants’ actions, and Avadel has
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`no other adequate remedy.
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`9
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`A.
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`43.
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`BACKGROUND
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`Legal Framework for New Drug Applications
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`The FDCA generally prohibits the sale of a “new drug” unless it has been proven
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`safe and effective. 21 U.S.C. § 355(a). The research and development necessary to secure
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`approval of a new drug generally requires extensive analytical tests, animal studies, and human
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`clinical safety and efficacy trials; takes many years; and is extremely costly. See id. § 355(b).
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`Based upon its research and development, a sponsor submits an NDA consisting of, inter alia,
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`manufacturing information and all analytical, preclinical, and clinical data. Id.
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`44.
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`The Hatch-Waxman Amendments of 1984 added more streamlined pathways to
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`NDA approval, including, as relevant to this case, the filing of a Section 505(b)(2) application. Id.
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`§ 355(b)(2). A Section 505(b)(2) application still requires a massive upfront investment, but the
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`applicant can rely on prior studies or investigations that “were not conducted by or for the
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`applicant” in order to obtain approval of a drug, which can produce savings of time and money in
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`drug development. Id.
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`45.
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`This pathway is typically used for drugs that are based on the same active ingredient
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`as—but which are not identical to—a previously approved drug. See id. But a Section 505(b)(2)
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`applicant must also, under certain circumstances, file a “patent certification” or a “patent
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`statement” regarding certain patents pertaining to the previously approved drug that was subject
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`to the prior investigations. 21 U.S.C. §§ 355(b)(2)(A), (b)(2)(B).
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`46.
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`Specifically, a Section 505(b)(2) NDA shall include a patent certification, “in the
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`opinion of the applicant and to the best of his knowledge, with respect to each patent which claims
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`the drug for which such investigations were conducted or which claims a use for such drug for
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`which the applicant is seeking approval under this subsection.” Id. § 355(b)(2)(A); see also 21
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`C.F.R. 314.50(i)(1)(iii)(B). If so, the applicant must make one of four certifications: “(i) that such
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`patent information has not been filed [with FDA], (ii) that such patent has expired, (iii) of the date
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`on which such patent will expire, or (iv) that such patent is invalid or will not be infringed by the
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`manufacture, use, or sale of the new drug . . . .” 21 U.S.C. § 355(b)(2)(A)(i)–(iv).
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`47.
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`The statute also provides an alternative pathway for Section 505(b)(2) applicants to
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`identify patents that do not fall within certification categories (i) through (iv), i.e., a “patent
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`statement.”
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`48.
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`Specifically, if a patent claims a use for the incumbent drug, but “does not claim a
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`use for which the applicant is seeking approval,” then the applicant must file—in lieu of a patent
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`certification—“a statement that the method of use patent does not claim such a use.” Id.
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`§ 355(b)(2)(B) (emphasis added); see also 21 C.F.R. § 314.50(i)(1)(iii)(A).
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`49.
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`To evaluate the patents for which a patent certification or statement may be
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`required, FDA instructs the applicant to consult FDA’s Approved Drug Products with Therapeutic
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`Equivalence Evaluations, known as the “Orange Book,” a database that publishes certain summary
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`information about patents associated with drugs. See Caraco Pharm. Laby’s, Ltd. v. Novo Nordisk
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`A/S, 566 U.S. 399, 405–06 (2012).
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`50.
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`In addition to patent numbers and expiration dates, the Orange Book contains “use
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`codes” submitted by incumbent patent owners that describe—in the owners’ own words—the uses
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`covered by their patents. Id.; see also 21 C.F.R. § 314.53(c)(2)(ii)(P)(3).
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`51.
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`Importantly, because FDA admits that it lacks expertise to evaluate patents, FDA
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`does not review the accuracy of Orange Book patent submissions, including use codes, that it
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`receives to determine whether they accurately reflect the patented drugs and uses. See Caraco,
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`566 U.S. at 405; Purepac Pharm. Co., 238 F. Supp. 2d at 196. Instead, FDA has assumed a “purely
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`ministerial” role, and “simply lists the patent information that it receives from brand
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`manufacturers . . . .” Purepac, 238 F. Supp. 2d at 196.
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`52.
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`A party wishing to dispute whether an Orange Book use code accurately describes
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`the scope of the underlying patent must first notify FDA and state the basis of its disagreement,
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`and FDA then asks the patent owner to confirm the accuracy of the listing. Id. at 197. However,
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`unless that owner voluntarily “‘withdraws or amends its patent information in response to FDA’s
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`request, the agency will not change the patent information’” in the Orange Book to render that
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`information accurate. Id. (quoting 21 C.F.R. § 314.53(f)).
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`53.
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`A certification may affect the date that FDA’s approval of a new drug takes effect.
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`For example, if a “paragraph IV” certification is filed claiming that “such patent is invalid or will
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`not be infringed” by the new drug, approval will not be made effective for a “thirty-month period”
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`if the patent owner initiates patent litigation within 45 days of the patent owner’s receipt of the
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`applicant’s notice of certification. 21 U.S.C. § 355(c)(3)(C). By contrast, there are no statutory
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`delays to the effective date of an NDA approval based on filing patent statements. See id.
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`§ 355(c)(3).
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`54.
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`Absent another limitation on approval (such as the stay referenced above), FDA
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`has a mandatory statutory duty to approve an NDA unless one of seven enumerated “grounds for
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`denying approval” is met, such as inadequate tests “to show whether or not such drug is safe for
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`use.” Id. § 355(c)(1)(A), (d).
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`55.
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`Specifically, the statute provides that “[w]ithin one hundred and eighty days after
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`the filing of an application . . . or such additional period as may be agreed upon by the Secretary
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`and the applicant,” the Secretary of the Department of Health and Human Services (“HHS”),
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`through FDA, “shall either—(A) approve the application if he then finds that none of the grounds
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`for denying approval specified in subsection (d) applies, or (B) give the applicant notice of an
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`opportunity for a hearing before the Secretary . . . on the question whether such application is
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`approvable.” Id. § 355(c) (emphasis added).
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`B.
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`56.
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`The Xyrem and Xywav REMS
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`Because of the potential for serious side effects and the risk of misuse, oxybate
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`products in the United States must be distributed under a REMS.
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`57.
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`A REMS “is a risk management plan that uses minimization strategies beyond
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`approved labeling to manage serious risks associated with a drug.” Kyle v. Linden Care, LLC, No.
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`19-CV-646-PB, 2020 WL 1853508, at *1 (D.N.H. Apr. 13, 2020). A REMS “can include a
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`Medication Guide or patient package insert, communication plan, one or more elements to assure
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`safe use, [and] an implementation system.” Id.
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`58.
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`FDA has discretion to determine whether a REMS is necessary “to ensure that the
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`benefits of the drug outweigh the risks of the drug.” 21 U.S.C. § 355-1(a)(1). In making that
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`determination, FDA considers multiple factors, including the benefits of the drug to patients, and
`
`the “seriousness of any known or potential adverse events that may be related to the drug.” Id.
`
`59.
`
`Jazz has always marketed its oxybate products, Xyrem and Xywav, pursuant to a
`
`REMS (or, prior to 2007, the predecessor to the REMS regime, a Risk Mitigation Action Plan
`
`(“RiskMAP”)) that has required a limited distribution system involving a single, central pharmacy
`
`that ships the drug directly to patients (the “Jazz REMS”). See In re Xyrem (Sodium Oxybate)
`
`Antitrust Litig., 555 F. Supp. 3d 829, 841 (N.D. Cal. 2021).
`
`60.
`
`Notably, Jazz has, for many years, used its REMS and REMS-related patents to
`
`maintain its monopoly over oxybate products. See In re Xyrem, 555 F. Supp. 3d at 840–44. It is
`
`widely acknowledged that “[b]randed drug manufacturers have . . . abused the REMS process to
`
`
`
`13
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`Case 1:22-cv-02159 Document 1 Filed 07/21/22 Page 14 of 27
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`
`
`
`block or delay entry by price-reducing generic competitors.” H.R. Rep. No. 116-55, pt. 2, at 4
`
`(2019).
`
`61.
`
`For example, in 2010, Jazz sued a competitor that sought to market a generic
`
`version of Xyrem for allegedly infringing, among other things, Jazz’s REMS-related patents. See
`
`generally Compl., Jazz Pharm., Inc. v. Roxane Laby’s, Inc., C.A. No. 10-6108 (D.N.J. Nov. 22,
`
`2010), ECF No. 1. The competitor counterclaimed, alleging those patents should not have been
`
`listed in the Orange Book and that Jazz was using the patents to improperly “block or delay
`
`approval” of generic oxybate drugs.
`
`62.
`
`In 2017, FDA criticized the “inconsistent position[s]” Jazz has taken with respect
`
`to multiple aspects of its REMS over the years, which have “suggest[ed] Jazz’s knowledge” that
`
`its REMS “could have the effect of preventing [ ] competition” for sodium oxybate products.” In
`
`re Xyrem (Sodium Oxybate) Antitrust Litig., No. 20-MD-02966-LHK, 2021 WL 3612497, at *6
`
`(N.D. Cal. Aug. 13, 2021 (quoting Mem. from Trueman Sharp, Deputy Director for the Office of
`
`Generic Drugs, FDA, to ANDAs for sodium oxybate oral solution products, et seq. (Jan. 17,
`
`2017)).
`
`63.
`
`And Jazz is now embroiled in litigation brought by a class of plaintiffs alleging that
`
`Jazz has used its REMS to prevent competitors from marketing generic sodium oxybate products.
`
`See In re Xyrem (Sodium Oxybate) Antitrust Litig., No. 3:20-md-02966-RS (N.D. Cal.); see also
`
`In re Xyrem, 555 F. Supp. 3d at 841 (“According to Plaintiffs, Jazz’s alleged abuse of the REMS
`
`process spanned nearly seven years beginning in late August 2008.”); Michael A. Carrier & Brenna
`
`Sooy, Five Solutions to the REMS Patent Problem, 97 B.U. L. Rev. 1661, 1681, 1689, 1704 (2017)
`
`(criticizing Jazz’s history of abusing its REMS-related patents to delay and prevent the entry of
`
`sodium oxybate drugs).
`
`
`
`14
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`Case 1:22-cv-02159 Document 1 Filed 07/21/22 Page 15 of 27
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`
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`C.
`
`64.
`
`FDA’s Initial Review of the LUMRYZ NDA
`
`On December 15, 2020, Avadel submitted an NDA for LUMRYZ under Section
`
`505(b)(2) of the FDCA.
`
`65.
`
`As part of that application, Avadel submitted a proposed REMS, in compliance
`
`with 21 U.S.C. § 355-1. Avadel submitted patent certifications for eight Jazz patents for Xyrem,
`
`stating that those patents had expired on June 22, 2020 or would expire on January 4, 2021. Avadel
`
`further submitted patent statements pursuant to 21 U.S.C. § 355(b)(2)(B) for five Jazz patents,
`
`averring that those patents do not claim a method of using sodium oxybate for which Avadel is
`
`seeking approval. Those certifications and statements are not at issue here.
`
`66.
`
`Avadel also submitted a patent statement regarding the ’963 patent, stating that this
`
`patent does not cover a method of using sodium oxybate for which Avadel is seeking approval of
`
`LUMRYZ. For the ’963 patent, Jazz has submitted a use code, U-1110, for inclusion in the Orange
`
`Book, which covers a “method of treating a patient with a prescription drug using a computer
`
`database in a computer system for distribution.”
`
`67.
`
`In its patent statement, Avadel explained that U-1110 does not cover any drug
`
`substance, drug product, or method of use such that any patent certification would be required,
`
`because the ’963 patent’s claims, according to U-1110, are directed to the use of a computer
`
`database in a computer system, not a drug, and Avadel’s proposed labeling for LUMRYZ describes
`
`no such requirement. Moreover, the statement explained, the proposed LUMRYZ REMS was
`
`“materially different” from the Xyrem REMS described in U-1110, because the LUMRYZ REMS
`
`
`
`15
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`Case 1:22-cv-02159 Document 1 Filed 07/21/22 Page 16 of 27
`Case 1:22-cv-02159 Document1 Filed 07/21/22 Page 16 of 27
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`“utilizes multiple secure, validated, separate, and distinct databases (as opposed to ‘a computer
`
`database’),”i.e., the single, centralized database covered by U-1110 and the ’963patent.!
`
`68.
`
`On February 26, 2021, FDA accepted the LUMRYZ NDAforfiling, stating that
`
`FDAhad “completed our filing review, and... determined that your application is sufficiently
`
`complete to permit a substantive review.” The NDA wastherefore deemed filed as of February
`
`13, 2021 “in accordance with 21 CFR 314.101(a),” meaning that FDA’s review was required to
`
`be complete by August 12, 2021. 21 U.S.C. § 355(c); 21 C.F.R. § 314.101(a)(2).
`
`69.
`
`But FDA insteadset a “goal date” to complete its review of the LUMRYZ NDA
`
`pursuant to the Prescription Drug User Fee Act (“PDUFA”) of “October 15, 2021.”
`
`70.
`
`Avadel assented to that extension of FDA’s time for review to October 15, 2021.
`
`Thus, per the FDCA, FDA haduntil, at the very latest, October 15, 2021, to either approve the
`
`LUMRYZ NDAor give Avadel notice of an opportunity for a hearing on whether the NDA is
`
`approvable. See 21 U.S.C. § 355(c)(1) (requiring FDAaction “[w]ithin one hundred and eighty
`
`days after the filing of an application undersubsection [355](b), or such additionalperiod as may
`
`be agreed uponby the Secretary and the applicant” (emphasis added)).
`
`72.
`
`! On March 25, 2022, Avadel sent FDA an updated patent statement, with materially identical
`content as the original statement regarding the ’963 patent.
`
`16
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`Case 1:22-cv-02159 Document 1 Filed 07/21/22 Page 17 of 27
`Case 1:22-cv-02159 Document1 Filed 07/21/22 Page 17 of 27
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`D.
`
`FDA/’s Unlawful Refusal to Act on the LUMRYZ NDA
`
`73.
`
`7A.
`
`Since the October 15, 2021, PDUFA date, Avadel has expeditiously responded to
`
`minoradditional requests from the Division, including, for example, administrative updates to the
`
`carton and container labeling,
`
`instructions for use, medication guide, and packaging, and
`
`submission of commitment dates for post-marketing non-clinical testing requirements.
`
`75.
`
`Notably, there is no indication that those minor requests should have or did impact
`
`FDA’s substantive review of the LUMRYZ NDA,and wereofthe sort that typically are finalized
`
`on the eve of a drug’s approval. They certainly provide no explanation for FDA’s many months
`
`ofdelay.
`
`76.|What followed were months of delay in which Avadel repeatedly sought clarity on
`
`when FDA’s final decision would issue, but FDA declined to provide a revised deadline forits
`
`_—z.oO2
`
`a
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`

`

`Case 1:22-cv-02159 Document 1 Filed 07/21/22 Page 18 of 27
`Case 1:22-cv-02159 Document1 Filed 07/21/22 Page 18 of 27
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`80.
`
`E.
`
`FDA/’s Patent Decision on Avadel’s Patent Statementto the ’963 Patent
`
`81.
`
`On May 24, 2022, 221 daysafterits statutory deadline to rendera final decision on
`
`the LUMRYZ NDAas a whole, either approving the NDA or granting a hearing on the
`
`approvability of the NDA, see 21 U.S.C. § 355(c)(1), FDA finally informed Avadel ofits final
`
`decision on one aspect of the NDA in FDA’s Patent Decision.
`
`82.
`
`The Patent Decision found that “Avadel is seeking approval of a condition of use
`
`that is claimed by the ’963 patent, as described by the U-1110 use code, and thus Avadel’s
`
`proposedsection 505(b)(2)(B) statement to address this patent is inappropriate.”
`
`83.|FDAordered Avadelto “provide an appropriate patent certification under 21 CFR
`
`314.50(i)(1)() to address the 963 patent.” FDA explainedthat its Patent Decision “constitutes a
`
`final decision” from FDA requiring Avadel to submit a patent certification.
`
`84.—Inits Patent Decision, FDA evaluated whether the LUMRYZ NDAseeks “approval
`
`for the protected use described in the U-