Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 1 of 103 PageID #: 1
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
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`REGENERON PHARMACEUTICALS, INC.
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`Plaintiff,
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`C.A. NO.:
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`JURY TRIAL DEMANDED
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`v.
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`AMGEN INC.
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`Defendant.
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`COMPLAINT
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`Plaintiff Regeneron Pharmaceuticals, Inc. (“Regeneron” or “Plaintiff”) files this
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`Complaint against Defendant Amgen Inc. (“Amgen” or “Defendant”) and alleges, upon
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`knowledge as to itself and otherwise upon information and belief, as follows:
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`NATURE OF ACTION
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`1.
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`This is an antitrust case involving an effort to eliminate from the market a life-
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`saving medicine that has served thousands of patients. Defendant Amgen is engaged in a persistent
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`exclusionary campaign to deny patients the life-saving benefits of Plaintiff Regeneron’s
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`cholesterol-reducing medication, Praluent® (alirocumab). And the reason is simple: for years,
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`Praluent® has been the only direct competitor to Amgen’s own drug Repatha® (evolocumab) and
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`Amgen is doing everything it can to avoid competing with Regeneron on the merits.
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`2.
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` Before commencing the unlawful, anticompetitive bundling scheme challenged
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`here, Amgen tried to enlist this Court to enter an injunction and force Praluent® off the market
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`entirely, after Praluent® was already approved and being used by patients. Amgen did so by
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`enforcing overbroad patents covering millions of biologic compounds, known as antibodies.
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`Amgen sought this injunction even though Praluent® is a novel, patented drug discovered and
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`developed by Regeneron with an entirely different chemical structure from Repatha® and with a
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`meaningfully differentiated efficacy and safety profile. In addition, Amgen directed its salesforce
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`to spread misinformation about Praluent® by communicating that Praluent® would be taken off the
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`market as a result of Amgen’s patent litigation campaign. Amgen’s patent challenge to Praluent®
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`was ultimately a failure before this Court and the Federal Circuit, which concluded that Amgen’s
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`patents were invalid and tried to cover compounds (like Praluent®) that Amgen had never
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`invented.1
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`3.
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`Now, Amgen has pivoted to an unlawful commercial strategy to try to exclude
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`Praluent® from the market. Amgen is engaged in an illegal, anticompetitive bundling scheme
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`forcing key intermediaries (who cover and pay for the majority of the cost of these drugs) to
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`jettison Regeneron’s Praluent® in favor of Amgen’s Repatha® in order to access substantial rebates
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`on entirely unrelated medications in Amgen’s portfolio that these intermediaries cannot avoid
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`purchasing. Importantly, one of these unrelated medications is a monopoly product Amgen very
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`recently acquired in a divestiture ordered by the Federal Trade Commission (“FTC”). When the
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`value of these massive, unavoidable bundled rebates is compared to the cost of Repatha® standing
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`alone, it becomes clear that Amgen is pricing Repatha® so that Regeneron cannot make a viable
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`financial offer to compete.
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`4.
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`This harm is not hypothetical. Amgen’s misconduct has devastated a product that
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`1 See Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080 (Fed. Cir. 2021); Amgen Inc. v. Sanofi, Aventisub
`LLC, 850 F. App’x 794, 796 (Fed. Cir. 2021), petition for cert. docketed, No. 21-757 (U.S. Nov. 22, 2021);
`Amgen Inc. v. Sanofi, No. CV 14-1317-RGA, 2019 WL 4058927, at *8 (D. Del. Aug. 28, 2019), aff’d sub
`nom. Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080 (Fed. Cir. 2021).
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`benefits thousands of patients who suffer from high cholesterol. Put simply, Amgen has made it
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`economically unfeasible for Regeneron to continue selling Praluent®. In 2022, the brand is
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`projected to be unprofitable, for the first time since Regeneron has marketed the product, due to
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`the anticompetitive marketplace conditions created by Amgen. Specifically, Amgen’s bundling
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`scheme has (i) artificially suppressed Praluent® sales by heavily restricting its market access, and
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`(ii) imposed artificial and substantially higher costs on the limited Praluent® sales where market
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`access is not totally cut off.
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`5.
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`Amgen’s scheme to exclude, hobble, and permanently handicap Praluent® has
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`caused Regeneron and the patients it serves significant injury, has harmed competition in the
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`relevant market, and violates federal and state antitrust, unfair competition, and tort laws.
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`Regeneron commences this action to redress these significant harms.
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`INTRODUCTION
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`6.
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`This case is about Amgen’s unlawful campaign to entrench its monopoly position
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`in the market for a class of drugs known as PCSK9 inhibitors (“PCSK9i”) that help high-risk
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`patients lower their low-density lipoprotein cholesterol (“LDL-C”)—often termed “bad
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`cholesterol”—and thereby reduce their risk of heart attack, stroke, and cardiovascular disease. See
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`Amgen, Inc. v. Sanofi, Aventisub LLC, 872 F.3d 1367, 1371 (Fed. Cir. 2017).
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`7.
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`Until recently, Regeneron’s Praluent® and Amgen’s Repatha® were the only two2
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`PCSK9 inhibitors approved by the U.S. Food and Drug Administration (“FDA”) available in the
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`United States. Although they work on the same overall therapeutic pathway—and neither is
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`interchangeable with other cholesterol-lowering medications like statins—Praluent® and Repatha®
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`are very different drugs both in terms of their chemical structures and their safety and efficacy
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`2 Emphasis is added in bold, italics, or underline, unless otherwise noted herein.
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`3
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`profiles. As Regeneron’s founder, President, and Chief Executive Officer (“CEO”), Dr. Leonard
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`Schleifer, MD, PhD, has testified, “[t]hese are incredibly different molecules, totally different in
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`structure, totally in their sequence, different in their label,” meaning that “the effect of taking one
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`off the market can be rather serious for patients.” Preliminary Injunction Hearing Transcript, at
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`93:12-15, Amgen Inc. v. Sanofi, No. CV 14-1317-RGA (D. Del. Aug. 8, 2019), ECF No. 1043 (“PI
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`Hearing Tr.”). Among the many unique medical benefits of Praluent® relative to Repatha® are:
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`Praluent®’s demonstrated meaningful mortality benefit in clinical trials; Praluent® is available in
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`a low-dose option preferred by doctors; Praluent® can be administered to patients with latex
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`allergies; Praluent® has been shown to reduce unstable angina requiring hospitalizations; and
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`Praluent® has been shown to decrease the need for apheresis (a technique for separating blood
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`components to treat certain illnesses). Given these benefits, Praluent® would take significant share
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`from Repatha® in the PCSK9i market3 if allowed to compete on its medical merits without the
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`exclusionary commercial barriers that Amgen has erected.
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`8.
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`Since the FDA’s approval of Praluent®, Amgen has sought by hook or by crook to
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`exclude Praluent® from the market in order to entrench Repatha®’s monopoly position. Amgen
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`first pursued an injunction against the sale of Praluent® through a patent litigation campaign in this
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`Court. But that strategy failed. So Amgen turned to an anticompetitive bundling scheme designed
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`to leverage sales of unrelated multibillion-dollar drugs in Amgen’s portfolio to artificially raise the
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`effective cost of Praluent® for key intermediaries. That illegal scheme is now having its intended
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`effect, depriving Praluent® of a critical mass of market share so that it is no longer a financially
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`viable competitor to Repatha®. Of course, the scheme also deprives patients of a unique
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`3 Unless otherwise noted, all references to the PCSK9i market refer to both the PCSK9i market and, in
`addition and in the alternative, to the Pharmacy-dispensed PCSK9i sub-market. See infra ¶¶ 102–108.
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`medication that neither Amgen nor anyone else other than Regeneron can provide.
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`9.
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`Amgen’s patent-enforcement campaign against Praluent® in this Court was based
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`on excessively broad patents claiming ownership of millions of antibodies—including Praluent®—
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`that Amgen had never invented. To be sure, Amgen has a patent that specifically covers Repatha®.
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`Amgen, 850 F. App’x at 796 (citing U.S. Patent 8,030,457). But Praluent® is vastly different from
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`Repatha® and, accordingly, Amgen’s Repatha® patent does not cover Praluent®. See id. So Amgen
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`instead resorted to obtaining and attempting to enforce patents that cover “millions of candidates
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`claimed with respect to multiple specific functions,” even though “it is clear that the claims are far
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`broader in functional diversity than the disclosed examples” Amgen provided. Amgen, 987 F.3d
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`at 1087–88. Amgen pursued litigation against Regeneron that went far beyond merely protecting
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`its patent on Repatha® from infringement; it instead sought to exclude Praluent®.
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`10.
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`Further illustrating Amgen’s intent in pursuing its patent claims, Amgen did not
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`merely seek damages from Regeneron. Amgen instead sought an injunction against the sale of
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`Praluent®, trying to take Praluent® off the market and out of the hands of the patients who needed
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`it. Amgen was clear about its motivation for seeking an injunction, alleging that Praluent®’s
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`“direct competition in this two-supplier market [was] causing Amgen to suffer price erosion,
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`reputational harm, lost sales, and lost market share.” Opening Br. in Support of Motion for
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`Permanent Injunctive Relief at 6, Amgen Inc. v. Sanofi, No. CV 14-1317-RGA, (D. Del. Apr. 27,
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`2016), ECF No. 340 (“PI Motion”). To further supplement this patent-litigation campaign,
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`Amgen’s sales representatives misleadingly promoted Repatha® with false claims to nurses,
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`physicians, and other medical practitioners that Praluent® would soon be removed from the market.
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`11.
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`Had Amgen obtained the injunction it requested, Repatha® would have become the
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`monopoly PCSK9 inhibitor product on the market, leaving Amgen with complete control over
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`prices and sales. And had Amgen prevailed in its attempt to enforce patents on “millions of
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`candidates” for future PCSK9 inhibitors, it would have effectively used the patent system to block
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`potential new market entrants and protect Repatha® from competition. Amgen, 987 F.3d at 1088.
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`12.
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`But after many years of litigation, the Court of Appeals for the Federal Circuit held
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`that Amgen’s patents were invalid, thereby stopping Amgen’s campaign to use the patent laws to
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`exclude Praluent® from the market and rid Repatha® of competition. The Federal Circuit forcefully
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`rejected Amgen’s efforts to durably “suppress innovation” by attempting “to control what it has
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`not invented”—namely, Praluent®. Amgen, 850 F. App’x at 796. In other words, Amgen told this
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`Court that it was trying to keep Praluent® off the market because competition was forcing Amgen
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`to lower prices and hurt its bottom line.
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`13.
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`Amgen’s efforts to control the PCSK9i market did not end in court: Amgen has
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`now crossed the line in the marketplace, implementing a multi-prong anticompetitive commercial
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`strategy to unlawfully cement its monopoly position in the PCSK9 inhibitor market. Amgen is
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`doing so by leveraging unrelated mega-products in its portfolio—including a recently acquired
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`monopoly product—whose combined sales are more than 36 times that of Praluent® to coerce
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`intermediaries who cover and pay for the majority of the cost of these drugs into eliminating
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`competition in the much smaller PCSK9i market. Amgen’s scheme prevents head-to-head
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`competition between Repatha® and Praluent®, allowing Repatha® to maintain and deepen its
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`monopoly position.
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`14.
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`Beginning in 2020, Amgen started conditioning rebates for two of its dominant
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`products in much larger, unrelated therapeutic areas upon exclusivity or practical exclusivity
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`for Repatha® on the formularies of the key insurers (“Third-Party Payors”), such as pharmacy
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`benefit managers (“PBMs”). And formulary positioning is critical for Praluent® and Repatha®,
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`because PCSK9i prescriptions are, in large part, ultimately paid for by Third-Party Payors, and the
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`Payors’ formularies drive which PCSK9 inhibitor—Praluent® or Repatha®—physicians will
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`prescribe.
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`15.
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`Amgen’s bundled-rebate scheme represents a radical departure from the norms of
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`competition in the PCSK9i market. Amgen and Regeneron for years had competed on the merits
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`of Praluent® and Repatha® for formulary positioning with PBMs. But all that changed in 2020,
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`when Amgen acquired Otezla®, an oral treatment for moderate-to-severe psoriasis that was so
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`dominant that the FTC ordered it divested as a condition for approving the Bristol Meyers
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`Squibb/Celgene merger. Amgen outbid other potential acquirers by paying an FTC-record $13.4
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`billion for Otezla®, which immediately became Amgen’s third-largest product. The acquisition of
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`this non-contestable monopoly product was key to launching Amgen’s anticompetitive scheme, as
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`Amgen quickly began using its new monopoly product—together with its other blockbuster
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`immunology product, Enbrel®—as the core pillars of its scheme to free itself of the need to
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`compete on price with Praluent®.
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`16.
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`The difference in scale between these blockbuster products and the relatively small
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`PCSK9i market is staggering. Praluent® generated just $356 million in total U.S. net sales for
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`2020 ($186 million) and 2021 ($170 million). Otezla® and Enbrel®, meanwhile, generated $12.8
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`billion in U.S. net sales in the same period, which is more than 36 times what Praluent® generated.
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`Put another way, Praluent®’s U.S. net sales amount to only 2.8 percent of what Otezla® and
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`Enbrel® generated. Therefore, the threat of paying just 3 percent more for Otezla® and Enbrel®
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`easily overwhelms the total amount of sales generated by Praluent®, leaving Payors trapped and
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`with no viable choice but to exclude Praluent® from their formularies.
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`17.
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`Accordingly, Amgen threatens to withhold significant rebates on these blockbuster
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`products unless Payors accept either outright exclusivity for Repatha® or else “equal” formulary
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`position. And “equal” is not really equal for several reasons, including the threat of an injunction
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`against the sale of Praluent® (while Amgen’s patent-litigation campaign was still pending before
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`the Federal Circuit), and the false claims made by Amgen’s sales force designed to dissuade
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`medical providers from prescribing Praluent®. Moreover, Amgen knows full well that it can
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`support its product with a massive sales force dedicated to Repatha® alone, as well as the huge
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`sales force it employs to cover its much larger portfolio of more than 20 products, that Regeneron
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`cannot possibly match. Thus even where Amgen does not achieve outright exclusivity for
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`Repatha®, Amgen can artificially tilt the playing field to influence physicians to prescribe
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`Repatha® over Praluent®, making even “equal” formulary position de facto exclusive.
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`18.
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`By conditioning rebates for Otezla® and Enbrel® on ensuring Repatha® exclusivity
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`or practical exclusivity on Third-Party Payor formularies, Amgen has unlawfully excluded
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`Praluent® by making it virtually impossible for Regeneron to meaningfully engage in the
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`competitive bidding process. Third-Party Payors, of course, are motivated by securing the lowest
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`net prices—that is, including rebates—across all of the products they cover. The threat of lost
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`rebates, and, in turn, increased prices for Otezla® and Enbrel® constitute a monetary penalty that
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`Regeneron cannot match and that Payors cannot afford. Those are substantially larger products
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`in unrelated classes where Regeneron markets no drugs and does not compete for the same
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`indications. Moreover, Regeneron has a relatively limited drug portfolio with only four products
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`that it markets, three of which are overwhelmingly not dispensed as prescription drug via
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`pharmacies and, thus, are not subject to significant coverage or reimbursement by Third-Party
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`Payors. So Regeneron does not have the practical ability to match Amgen’s multi-product bundled
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`rebate offer with its own multi-product bundled rebate offer.
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`19.
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`Amgen’s bundled rebate scheme further excludes competition by pricing Repatha®
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`such that Regeneron cannot make a financially viable case for Praluent®. Repatha® generated
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`nearly $1.02 billion for Amgen in U.S. net sales for 2020 ($459 million) and 2021 ($557 million),
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`which is dwarfed by the $12.8 billion in U.S. net sales generated by Otezla® and Enbrel® in that
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`same period. Given this enormous gap in sales, and after allocating the entirety of Amgen’s
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`massive bundled rebates across these three products to Repatha®, Amgen is pricing Repatha®
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`below its costs. Even though Amgen is pricing Repatha® below cost, Amgen is still not losing
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`money overall, given the much larger sales associated with the other products in the bundle.
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`Further, Amgen has increased the penalty to Third-Party Payors for deviating from its bundle by
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`ratcheting up the pre-rebate list prices of Otezla® and Enbrel® (as well as Repatha®), thereby
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`coercing Third-Party Payors to take the bundle and exclude Praluent® in favor of Repatha®. So
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`unlike a “loss leader” on a competitive non-monopoly product, Amgen stands only to gain from
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`its bundle. As Amgen’s failed patent-litigation campaign to take Praluent® off the market
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`illustrates, Amgen’s purpose and intent in initiating and executing on this anticompetitive pricing
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`and bundled rebate scheme has been to foreclose Regeneron’s Praluent® from a significant share
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`of the PCSK9i market in order to ultimately eliminate this competition for Repatha® altogether.
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`20.
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`Amgen’s scheme has worked, and the results of Amgen’s unlawful exclusionary
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`bundling are already substantial and will continue to grow worse. For example, at one Third-Party
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`Payor, Praluent®’s share of PCSK9i sales has plummeted more than 60 percent in just six months.
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`In aggregate, Praluent® has been substantially foreclosed from the PCSK9i market with no
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`coverage from Third-Party Payors reimbursing 51 percent of prescriptions. As a result of
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`Amgen’s anticompetitive practices, in 2022, Regeneron stands to lose money for the first time on
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`the formerly profitable Praluent®. In 2020 and 2021, Regeneron took painful cost cutting measures
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`to eliminate its Praluent® sales force, stop future research and development for Praluent®, and
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`significantly cut back its marketing and other expenses, in order to mitigate against Amgen’s
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`practices. Put simply, there is nothing left to cut.
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`21.
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`But that is not all. At this significant level of restricted access, there are major
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`spillover effects that will further harm Regeneron, because many physicians will simply prescribe
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`the only product with widespread coverage. Amgen’s ability to leverage its much larger sales
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`force across its portfolio of drug products to promote Repatha®, not to mention its willingness to
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`use outright misrepresentation to steer prescribers away from Praluent®, therefore exacerbates
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`these spillover effects. These compounding factors have already artificially limited Praluent®’s
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`market access and will continue to cripple Regeneron’s ability to remain a viable competitor.
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`Further, if Amgen’s unlawful anticompetitive tactics remain unrestrained by the law, potential new
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`entrants will foresee their future foreclosure and refuse to invest (unless they are one of a few giant
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`pharmaceutical firms or have products that would not compete as a prescription drug dispensed
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`via pharmacies).
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`22.
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`The harm to competition, to Regeneron, and, especially, to patients resulting from
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`Amgen’s unlawful anticompetitive behavior is significant. Because of Amgen’s exclusion of
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`Praluent®, patients and physicians are deprived of choice in PCSK9 inhibitor treatments and
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`competition is harmed by the diminution of competition and resultant higher prices for Repatha®
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`in the long term. Regeneron accordingly files this suit to redress this unlawful anticompetitive
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`behavior and harm to competition.
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`PARTIES
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`23.
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`Plaintiff Regeneron is a corporation organized and existing under the laws of the
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`State of New York with its principal place of business located at 777 Old Saw Mill River Road,
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`Tarrytown, New York 10591. Regeneron is in the business of inventing, developing,
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`manufacturing, and marketing a variety of innovative pharmaceutical products. Regeneron
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`markets and distributes Praluent® in the United States.
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`24.
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`Defendant Amgen is a corporation organized and existing under the laws of the
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`State of Delaware with its principal place of business located at One Amgen Center Drive,
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`Thousand Oaks, California 91320. Amgen markets and distributes Repatha®, Enbrel®, and
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`Otezla® in the United States.
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`JURISDICTION AND VENUE
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`25.
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`This Court has subject matter jurisdiction over all claims asserted against Defendant
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`pursuant to 28 U.S.C. § 1331, 28 U.S.C. § 1337(a), 15 U.S.C. § 4, 15 U.S.C. § 15, and 15 U.S.C.
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`§ 26. This Court has supplemental jurisdiction over Plaintiff’s pendent state law claims pursuant
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`to 28 U.S.C. § 1367.
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`26.
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`This Court has personal jurisdiction over Amgen under the U.S. Constitution and
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`nationwide contacts under Section 12 of the Clayton Act, 15 U.S.C. § 22.
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`27.
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`Venue is proper in this District under Section 12 of the Clayton Act, 15 U.S.C. §
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`22, and under 28 U.S.C. § 1391(b) and (c).
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`28.
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`For personal jurisdiction and venue purposes, Amgen may be found in or transacts
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`business in this District, including through the marketing and sale of Repatha®, Enbrel®, and
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`Otzela®. Amgen’s unlawful behavior was specifically intended to, has had, and will continue to
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`have an anticompetitive effect and impact on Regeneron and U.S. consumers in this District, and
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`elsewhere. Additionally, Amgen’s patent litigation campaign against Regeneron was pursued in
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`this District, including the sought-after injunction that, in turn, Amgen’s sales representatives used
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`to discourage physicians from prescribing Praluent® in favor of Repatha®.
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`INTERSTATE COMMERCE
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`29.
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`The commercialization, development, manufacturing, marketing, sale, and
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`distribution of Praluent®, Repatha®, Enbrel®, and Otezla® occurs in interstate commerce.
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`FACTUAL BACKGROUND
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`A.
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`Treatment of High Low-Density Lipoprotein Cholesterol
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`i.
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`PCSK9 Inhibitors
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`30.
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`High systemic levels of LDL-C or “bad cholesterol” can lead to heart attacks,
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`strokes, and cardiovascular disease. PCSK9 inhibitors eliminate LDL-C by leveraging the body’s
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`natural way of removing LDL-C from the blood. In particular, LDL-C receptors, which are located
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`on the surface of liver cells, are responsible for extracting LDL-C from the bloodstream. The
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`PCSK9 protein, however, regulates this process by binding to and causing the degradation of these
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`LDL-C receptors inside the liver cells. PCSK9 inhibitors prevent PCSK9 from binding to the
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`LDL-C receptors, so the receptors are not degraded inside the cell. Therefore, the receptors can
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`return to the cell surface and continue the body’s natural process of removing LDL-C from the
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`bloodstream. See Amgen, 987 F.3d at 1082.
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`31. While there are other FDA-approved treatments for lowering cholesterol, none is
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`reasonably interchangeable with PCSK9 inhibitors. Doctors have historically treated high LDL-
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`C levels with drugs called statins. In many cases, however, statins are not enough to bring a
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`patient’s LDL-C to a healthy level and/or may not be tolerated by patients due to side effects. In
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`those cases, PCSK9 inhibitors are critical. PCSK9 inhibitors therefore serve a unique patient
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`population. Doctors typically prescribe only PCSK9 inhibitors for patients at a high risk for
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`cardiovascular problems, such as individuals with familial hypercholesterolemia (“FH”), people
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`at high risk who are unable to lower their cholesterol using other drugs, or people who are statin-
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`intolerant. Clinical trials have shown that PCSK9 inhibitors can reduce cholesterol by 45 or 60
`
`percent depending on the dose, and can reduce the risk of heart attack, stroke, and, in the case of
`
`Regeneron’s Praluent®, unstable angina requiring hospitalization in adults with established
`
`
`
`
`12
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 13 of 103 PageID #: 13
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`
`
`
`cardiovascular disease.4
`
`a.
`
`Regeneron’s Praluent®
`
`32.
`
`In 2015, Praluent®, which Regeneron invented and brought to market, became the
`
`first PCSK9 inhibitor to obtain FDA approval. Praluent® is a monoclonal antibody that specifically
`
`targets and binds to PCSK9 and thereby effectively prevents the patient’s body from stopping the
`
`degradation of bad cholesterol. Praluent® is a unique and highly effective molecule that is
`
`structurally and functionally distinct from Repatha® and offers distinctive medical benefits that
`
`Repatha® does not provide. See Amgen, 872 F.3d at 1372.
`
`33.
`
`Praluent® “targets PCSK9 to prevent it from binding to and destroying” LDL-C
`
`receptors. Id. In this way, it permits the receptors to “extract LDL-C thereby lowering overall
`
`LDL-C levels.” Id. Specifically, when Praluent® binds PCSK9, it almost entirely covers the exact
`
`region on PCSK9 to which the LDL-C receptor binds. In 2011, the U.S. Patent and Trademark
`
`Office recognized the novelty of Praluent® and issued Regeneron a patent that covers the precise
`
`amino acid sequence of Praluent®. Id.; see U.S. Patent No. 8,062,640. The FDA approved
`
`Praluent® in July 2015, allowing Praluent® to become the first PCSK9 antibody marketed in the
`
`United States. See Amgen, 872 F.3d at 1372.
`
`34.
`
`Praluent® is the only PCSK9 inhibitor that demonstrated in clinical trials a
`
`meaningful mortality benefit. This means that fewer patients died taking Praluent® than taking a
`
`placebo. As reported in the New England Journal of Medicine, Praluent® showed a 15 percent
`
`reduction in all-cause mortality and a 29 percent reduction in all-cause death for higher-risk
`
`
`4 Regeneron Pharmaceuticals, Praluent®
`insert
`package
`(alirocumab)
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125559s029s030lbl.pdf.
`
`(April
`
`2021),
`
`
`
`
`13
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 14 of 103 PageID #: 14
`
`
`
`
`patients whose baseline LDL-C is equal to or greater than 100 mg/dL.5 These results were so
`
`notable that the FDA allowed Regeneron to include data describing this distinguishing benefit in
`
`its label.6
`
`35.
`
`Praluent® is available in two dosage options: a 75 mg low dose and 150 mg high
`
`dose. These dosage options provide doctors and patients with flexibility to choose either less LDL-
`
`C lowering with the low dose or more LDL-C lowering with the high dose. This optionality is
`
`critical. As a practical matter, doctors prefer the low dose and prescribe it more frequently than
`
`the high dose. Additionally, physicians—including members of the FDA’s advisory panel for
`
`Praluent® and Repatha®—have expressed concerns about the unknown long-term effects of LDL-
`
`C levels that are too low.7 Praluent® thus provides doctors with the option of prescribing a low
`
`dose where appropriate—i.e., prescribing only as much medication as is necessary to treat the
`
`patient—and preventing any potential long-term effects that could arise from too low LDL-C
`
`levels.
`
`b.
`
`Amgen’s Repatha®
`
`36.
`
`Amgen, too, developed a PCSK9 inhibitor and obtained FDA approval for the drug
`
`it markets as Repatha®. Amgen, 872 F.3d at 1371. Like Praluent®, Repatha® “targets PCSK9 to
`
`prevent it from destroying” LDL-C receptors. Id. Unlike Praluent®, however, Repatha® only
`
`minimally binds the region on PCSK9 to which the LDL-C receptor binds.
`
`
`5 Gregory G. Schwartz, et al., Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome,
`379 New Eng. J. Med. 2097–2107, at Table 2 (2018).
`6 Regeneron Pharmaceuticals, Praluent® (alirocumab) package
`insert, at 21 (April 2021),
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125559s029s030lbl.pdf.
`7 See Response of Amicus Curiae Practitioners Who Currently Treat Patients with Praluent in Support of
`Appellants’ Motion for Stay Pending Appeal, at 7, filed in Sanofi v. Amgen, Inc., No. 17-1480, (Fed. Cir.
`Jan. 24, 2017), ECF No. 40 (“[T]he amicus practitioners believe that forcing patients to pursue a different
`and higher dosage course of treatment would be medically unnecessary.”).
`
`
`
`
`14
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 15 of 103 PageID #: 15
`
`
`
`
`37.
`
`Repatha® further lacks a number of Praluent®’s key benefits. First, Repatha®’s
`
`clinical trials did not show a mortality benefit.8 In fact, the results showed a slight increase in all-
`
`cause death and cardiovascular death in patients taking Repatha® as compared with patients taking
`
`placebo.9
`
`38.
`
`Second, Repatha® is available only in higher doses—a 140 mg/mL dose and a
`
`420mg/3.5mL dose. Therefore, unlike Praluent®, Repatha® does not provide doctors and patients
`
`with a 75 mg dose option or any other low dose equivalent.
`
`39.
`
`Third, Repatha® is administered via a single-use prefilled syringe, a single-use
`
`SureClick autoinjector, or a single-use Pushtronex system (which is an on-body infuser with a
`
`prefilled cartridge)—each of which presents certain disadvantages not presented by Praluent®’s
`
`administration. Specifically, the Repatha® label warns latex-sensitive patients that the “needle
`
`cover of the glass single-dose prefilled syringe and the single-dose prefilled autoinjector contain
`
`dry natural rubber (a derivative of latex) which may cause an allergic reaction in individuals
`
`sensitive to latex.”10 As a result, certain practitioners believe that, “due to the risks associated with
`
`Repatha, patients with latex allergies or rubber allergies should not be started on Repatha.”11
`
`Praluent®, on the other hand, is administered via a single-dose pre-filled pen with a “needle shield
`
`[that] is not made with natural rubber latex” and is therefore a safer option for patients with latex
`
`
`8 Marc S. Sabatine, et al., Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease,
`376 New England J. Med. 1713–1722, at Table 2 (2017).
`9 Id.
`Repatha®
`3
`at
`insert,
`10
`package
`(evolocumab)
`Inc.,
`Amgen,
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125522s029s031lbl.pdf.
`11 See Response of Amicus Curiae Practitioners Who Currently Treat Patients with Praluent in Support of
`Appellants’ Motion for Stay Pending Appeal, at 7, filed in Sanofi v. Amgen, Inc., No. 17-1480, (Fed. Cir.
`Jan. 24, 2017), ECF No. 40.
`
`2021),
`
`(Sept.
`
`
`
`
`15
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 16 of 103 PageID #: 16
`
`
`
`
`sensitivities.12 Praluent®’s single-dose pre-filled pen is also faster and far easier to use than
`
`Repatha®’s single-use Pushtronex system, which requires the patient to remain still for five
`
`minutes following dosage administration.13
`
`40.
`
`Fourth, Praluent®’s clinical trial data demonstrated a 39 percent reduction in
`
`unstable angina requiring hospitalizations,14 whereas Repatha® s