throbber
Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 1 of 103 PageID #: 1
`
`
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`
`REGENERON PHARMACEUTICALS, INC.
`
`
`Plaintiff,
`
`
`
`
`
`C.A. NO.:
`
`
`JURY TRIAL DEMANDED
`
`
`
`
`v.
`
`
`AMGEN INC.
`
`
`
`
`Defendant.
`
`
`
`COMPLAINT
`
`Plaintiff Regeneron Pharmaceuticals, Inc. (“Regeneron” or “Plaintiff”) files this
`
`Complaint against Defendant Amgen Inc. (“Amgen” or “Defendant”) and alleges, upon
`
`knowledge as to itself and otherwise upon information and belief, as follows:
`
`NATURE OF ACTION
`
`1.
`
`This is an antitrust case involving an effort to eliminate from the market a life-
`
`saving medicine that has served thousands of patients. Defendant Amgen is engaged in a persistent
`
`exclusionary campaign to deny patients the life-saving benefits of Plaintiff Regeneron’s
`
`cholesterol-reducing medication, Praluent® (alirocumab). And the reason is simple: for years,
`
`Praluent® has been the only direct competitor to Amgen’s own drug Repatha® (evolocumab) and
`
`Amgen is doing everything it can to avoid competing with Regeneron on the merits.
`
`2.
`
` Before commencing the unlawful, anticompetitive bundling scheme challenged
`
`here, Amgen tried to enlist this Court to enter an injunction and force Praluent® off the market
`
`entirely, after Praluent® was already approved and being used by patients. Amgen did so by
`
`
`
`
`
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 2 of 103 PageID #: 2
`
`
`
`
`enforcing overbroad patents covering millions of biologic compounds, known as antibodies.
`
`Amgen sought this injunction even though Praluent® is a novel, patented drug discovered and
`
`developed by Regeneron with an entirely different chemical structure from Repatha® and with a
`
`meaningfully differentiated efficacy and safety profile. In addition, Amgen directed its salesforce
`
`to spread misinformation about Praluent® by communicating that Praluent® would be taken off the
`
`market as a result of Amgen’s patent litigation campaign. Amgen’s patent challenge to Praluent®
`
`was ultimately a failure before this Court and the Federal Circuit, which concluded that Amgen’s
`
`patents were invalid and tried to cover compounds (like Praluent®) that Amgen had never
`
`invented.1
`
`3.
`
`Now, Amgen has pivoted to an unlawful commercial strategy to try to exclude
`
`Praluent® from the market. Amgen is engaged in an illegal, anticompetitive bundling scheme
`
`forcing key intermediaries (who cover and pay for the majority of the cost of these drugs) to
`
`jettison Regeneron’s Praluent® in favor of Amgen’s Repatha® in order to access substantial rebates
`
`on entirely unrelated medications in Amgen’s portfolio that these intermediaries cannot avoid
`
`purchasing. Importantly, one of these unrelated medications is a monopoly product Amgen very
`
`recently acquired in a divestiture ordered by the Federal Trade Commission (“FTC”). When the
`
`value of these massive, unavoidable bundled rebates is compared to the cost of Repatha® standing
`
`alone, it becomes clear that Amgen is pricing Repatha® so that Regeneron cannot make a viable
`
`financial offer to compete.
`
`4.
`
`This harm is not hypothetical. Amgen’s misconduct has devastated a product that
`
`
`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).
`
`
`
`
`2
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 3 of 103 PageID #: 3
`
`
`
`
`benefits thousands of patients who suffer from high cholesterol. Put simply, Amgen has made it
`
`economically unfeasible for Regeneron to continue selling Praluent®. In 2022, the brand is
`
`projected to be unprofitable, for the first time since Regeneron has marketed the product, due to
`
`the anticompetitive marketplace conditions created by Amgen. Specifically, Amgen’s bundling
`
`scheme has (i) artificially suppressed Praluent® sales by heavily restricting its market access, and
`
`(ii) imposed artificial and substantially higher costs on the limited Praluent® sales where market
`
`access is not totally cut off.
`
`5.
`
`Amgen’s scheme to exclude, hobble, and permanently handicap Praluent® has
`
`caused Regeneron and the patients it serves significant injury, has harmed competition in the
`
`relevant market, and violates federal and state antitrust, unfair competition, and tort laws.
`
`Regeneron commences this action to redress these significant harms.
`
`INTRODUCTION
`
`6.
`
`This case is about Amgen’s unlawful campaign to entrench its monopoly position
`
`in the market for a class of drugs known as PCSK9 inhibitors (“PCSK9i”) that help high-risk
`
`patients lower their low-density lipoprotein cholesterol (“LDL-C”)—often termed “bad
`
`cholesterol”—and thereby reduce their risk of heart attack, stroke, and cardiovascular disease. See
`
`Amgen, Inc. v. Sanofi, Aventisub LLC, 872 F.3d 1367, 1371 (Fed. Cir. 2017).
`
`7.
`
`Until recently, Regeneron’s Praluent® and Amgen’s Repatha® were the only two2
`
`PCSK9 inhibitors approved by the U.S. Food and Drug Administration (“FDA”) available in the
`
`United States. Although they work on the same overall therapeutic pathway—and neither is
`
`interchangeable with other cholesterol-lowering medications like statins—Praluent® and Repatha®
`
`are very different drugs both in terms of their chemical structures and their safety and efficacy
`
`
`2 Emphasis is added in bold, italics, or underline, unless otherwise noted herein.
`
`
`
`
`3
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 4 of 103 PageID #: 4
`
`
`
`
`profiles. As Regeneron’s founder, President, and Chief Executive Officer (“CEO”), Dr. Leonard
`
`Schleifer, MD, PhD, has testified, “[t]hese are incredibly different molecules, totally different in
`
`structure, totally in their sequence, different in their label,” meaning that “the effect of taking one
`
`off the market can be rather serious for patients.” Preliminary Injunction Hearing Transcript, at
`
`93:12-15, Amgen Inc. v. Sanofi, No. CV 14-1317-RGA (D. Del. Aug. 8, 2019), ECF No. 1043 (“PI
`
`Hearing Tr.”). Among the many unique medical benefits of Praluent® relative to Repatha® are:
`
`Praluent®’s demonstrated meaningful mortality benefit in clinical trials; Praluent® is available in
`
`a low-dose option preferred by doctors; Praluent® can be administered to patients with latex
`
`allergies; Praluent® has been shown to reduce unstable angina requiring hospitalizations; and
`
`Praluent® has been shown to decrease the need for apheresis (a technique for separating blood
`
`components to treat certain illnesses). Given these benefits, Praluent® would take significant share
`
`from Repatha® in the PCSK9i market3 if allowed to compete on its medical merits without the
`
`exclusionary commercial barriers that Amgen has erected.
`
`8.
`
`Since the FDA’s approval of Praluent®, Amgen has sought by hook or by crook to
`
`exclude Praluent® from the market in order to entrench Repatha®’s monopoly position. Amgen
`
`first pursued an injunction against the sale of Praluent® through a patent litigation campaign in this
`
`Court. But that strategy failed. So Amgen turned to an anticompetitive bundling scheme designed
`
`to leverage sales of unrelated multibillion-dollar drugs in Amgen’s portfolio to artificially raise the
`
`effective cost of Praluent® for key intermediaries. That illegal scheme is now having its intended
`
`effect, depriving Praluent® of a critical mass of market share so that it is no longer a financially
`
`viable competitor to Repatha®. Of course, the scheme also deprives patients of a unique
`
`
`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.
`
`
`
`
`4
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 5 of 103 PageID #: 5
`
`
`
`
`medication that neither Amgen nor anyone else other than Regeneron can provide.
`
`9.
`
`Amgen’s patent-enforcement campaign against Praluent® in this Court was based
`
`on excessively broad patents claiming ownership of millions of antibodies—including Praluent®—
`
`that Amgen had never invented. To be sure, Amgen has a patent that specifically covers Repatha®.
`
`Amgen, 850 F. App’x at 796 (citing U.S. Patent 8,030,457). But Praluent® is vastly different from
`
`Repatha® and, accordingly, Amgen’s Repatha® patent does not cover Praluent®. See id. So Amgen
`
`instead resorted to obtaining and attempting to enforce patents that cover “millions of candidates
`
`claimed with respect to multiple specific functions,” even though “it is clear that the claims are far
`
`broader in functional diversity than the disclosed examples” Amgen provided. Amgen, 987 F.3d
`
`at 1087–88. Amgen pursued litigation against Regeneron that went far beyond merely protecting
`
`its patent on Repatha® from infringement; it instead sought to exclude Praluent®.
`
`10.
`
`Further illustrating Amgen’s intent in pursuing its patent claims, Amgen did not
`
`merely seek damages from Regeneron. Amgen instead sought an injunction against the sale of
`
`Praluent®, trying to take Praluent® off the market and out of the hands of the patients who needed
`
`it. Amgen was clear about its motivation for seeking an injunction, alleging that Praluent®’s
`
`“direct competition in this two-supplier market [was] causing Amgen to suffer price erosion,
`
`reputational harm, lost sales, and lost market share.” Opening Br. in Support of Motion for
`
`Permanent Injunctive Relief at 6, Amgen Inc. v. Sanofi, No. CV 14-1317-RGA, (D. Del. Apr. 27,
`
`2016), ECF No. 340 (“PI Motion”). To further supplement this patent-litigation campaign,
`
`Amgen’s sales representatives misleadingly promoted Repatha® with false claims to nurses,
`
`physicians, and other medical practitioners that Praluent® would soon be removed from the market.
`
`11.
`
`Had Amgen obtained the injunction it requested, Repatha® would have become the
`
`monopoly PCSK9 inhibitor product on the market, leaving Amgen with complete control over
`
`
`
`
`5
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 6 of 103 PageID #: 6
`
`
`
`
`prices and sales. And had Amgen prevailed in its attempt to enforce patents on “millions of
`
`candidates” for future PCSK9 inhibitors, it would have effectively used the patent system to block
`
`potential new market entrants and protect Repatha® from competition. Amgen, 987 F.3d at 1088.
`
`12.
`
`But after many years of litigation, the Court of Appeals for the Federal Circuit held
`
`that Amgen’s patents were invalid, thereby stopping Amgen’s campaign to use the patent laws to
`
`exclude Praluent® from the market and rid Repatha® of competition. The Federal Circuit forcefully
`
`rejected Amgen’s efforts to durably “suppress innovation” by attempting “to control what it has
`
`not invented”—namely, Praluent®. Amgen, 850 F. App’x at 796. In other words, Amgen told this
`
`Court that it was trying to keep Praluent® off the market because competition was forcing Amgen
`
`to lower prices and hurt its bottom line.
`
`13.
`
`Amgen’s efforts to control the PCSK9i market did not end in court: Amgen has
`
`now crossed the line in the marketplace, implementing a multi-prong anticompetitive commercial
`
`strategy to unlawfully cement its monopoly position in the PCSK9 inhibitor market. Amgen is
`
`doing so by leveraging unrelated mega-products in its portfolio—including a recently acquired
`
`monopoly product—whose combined sales are more than 36 times that of Praluent® to coerce
`
`intermediaries who cover and pay for the majority of the cost of these drugs into eliminating
`
`competition in the much smaller PCSK9i market. Amgen’s scheme prevents head-to-head
`
`competition between Repatha® and Praluent®, allowing Repatha® to maintain and deepen its
`
`monopoly position.
`
`14.
`
`Beginning in 2020, Amgen started conditioning rebates for two of its dominant
`
`products in much larger, unrelated therapeutic areas upon exclusivity or practical exclusivity
`
`for Repatha® on the formularies of the key insurers (“Third-Party Payors”), such as pharmacy
`
`benefit managers (“PBMs”). And formulary positioning is critical for Praluent® and Repatha®,
`
`
`
`
`6
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 7 of 103 PageID #: 7
`
`
`
`
`because PCSK9i prescriptions are, in large part, ultimately paid for by Third-Party Payors, and the
`
`Payors’ formularies drive which PCSK9 inhibitor—Praluent® or Repatha®—physicians will
`
`prescribe.
`
`15.
`
`Amgen’s bundled-rebate scheme represents a radical departure from the norms of
`
`competition in the PCSK9i market. Amgen and Regeneron for years had competed on the merits
`
`of Praluent® and Repatha® for formulary positioning with PBMs. But all that changed in 2020,
`
`when Amgen acquired Otezla®, an oral treatment for moderate-to-severe psoriasis that was so
`
`dominant that the FTC ordered it divested as a condition for approving the Bristol Meyers
`
`Squibb/Celgene merger. Amgen outbid other potential acquirers by paying an FTC-record $13.4
`
`billion for Otezla®, which immediately became Amgen’s third-largest product. The acquisition of
`
`this non-contestable monopoly product was key to launching Amgen’s anticompetitive scheme, as
`
`Amgen quickly began using its new monopoly product—together with its other blockbuster
`
`immunology product, Enbrel®—as the core pillars of its scheme to free itself of the need to
`
`compete on price with Praluent®.
`
`16.
`
`The difference in scale between these blockbuster products and the relatively small
`
`PCSK9i market is staggering. Praluent® generated just $356 million in total U.S. net sales for
`
`2020 ($186 million) and 2021 ($170 million). Otezla® and Enbrel®, meanwhile, generated $12.8
`
`billion in U.S. net sales in the same period, which is more than 36 times what Praluent® generated.
`
`Put another way, Praluent®’s U.S. net sales amount to only 2.8 percent of what Otezla® and
`
`Enbrel® generated. Therefore, the threat of paying just 3 percent more for Otezla® and Enbrel®
`
`easily overwhelms the total amount of sales generated by Praluent®, leaving Payors trapped and
`
`with no viable choice but to exclude Praluent® from their formularies.
`
`17.
`
`Accordingly, Amgen threatens to withhold significant rebates on these blockbuster
`
`
`
`
`7
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 8 of 103 PageID #: 8
`
`
`
`
`products unless Payors accept either outright exclusivity for Repatha® or else “equal” formulary
`
`position. And “equal” is not really equal for several reasons, including the threat of an injunction
`
`against the sale of Praluent® (while Amgen’s patent-litigation campaign was still pending before
`
`the Federal Circuit), and the false claims made by Amgen’s sales force designed to dissuade
`
`medical providers from prescribing Praluent®. Moreover, Amgen knows full well that it can
`
`support its product with a massive sales force dedicated to Repatha® alone, as well as the huge
`
`sales force it employs to cover its much larger portfolio of more than 20 products, that Regeneron
`
`cannot possibly match. Thus even where Amgen does not achieve outright exclusivity for
`
`Repatha®, Amgen can artificially tilt the playing field to influence physicians to prescribe
`
`Repatha® over Praluent®, making even “equal” formulary position de facto exclusive.
`
`18.
`
`By conditioning rebates for Otezla® and Enbrel® on ensuring Repatha® exclusivity
`
`or practical exclusivity on Third-Party Payor formularies, Amgen has unlawfully excluded
`
`Praluent® by making it virtually impossible for Regeneron to meaningfully engage in the
`
`competitive bidding process. Third-Party Payors, of course, are motivated by securing the lowest
`
`net prices—that is, including rebates—across all of the products they cover. The threat of lost
`
`rebates, and, in turn, increased prices for Otezla® and Enbrel® constitute a monetary penalty that
`
`Regeneron cannot match and that Payors cannot afford. Those are substantially larger products
`
`in unrelated classes where Regeneron markets no drugs and does not compete for the same
`
`indications. Moreover, Regeneron has a relatively limited drug portfolio with only four products
`
`that it markets, three of which are overwhelmingly not dispensed as prescription drug via
`
`pharmacies and, thus, are not subject to significant coverage or reimbursement by Third-Party
`
`Payors. So Regeneron does not have the practical ability to match Amgen’s multi-product bundled
`
`rebate offer with its own multi-product bundled rebate offer.
`
`
`
`
`8
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 9 of 103 PageID #: 9
`
`
`
`
`19.
`
`Amgen’s bundled rebate scheme further excludes competition by pricing Repatha®
`
`such that Regeneron cannot make a financially viable case for Praluent®. Repatha® generated
`
`nearly $1.02 billion for Amgen in U.S. net sales for 2020 ($459 million) and 2021 ($557 million),
`
`which is dwarfed by the $12.8 billion in U.S. net sales generated by Otezla® and Enbrel® in that
`
`same period. Given this enormous gap in sales, and after allocating the entirety of Amgen’s
`
`massive bundled rebates across these three products to Repatha®, Amgen is pricing Repatha®
`
`below its costs. Even though Amgen is pricing Repatha® below cost, Amgen is still not losing
`
`money overall, given the much larger sales associated with the other products in the bundle.
`
`Further, Amgen has increased the penalty to Third-Party Payors for deviating from its bundle by
`
`ratcheting up the pre-rebate list prices of Otezla® and Enbrel® (as well as Repatha®), thereby
`
`coercing Third-Party Payors to take the bundle and exclude Praluent® in favor of Repatha®. So
`
`unlike a “loss leader” on a competitive non-monopoly product, Amgen stands only to gain from
`
`its bundle. As Amgen’s failed patent-litigation campaign to take Praluent® off the market
`
`illustrates, Amgen’s purpose and intent in initiating and executing on this anticompetitive pricing
`
`and bundled rebate scheme has been to foreclose Regeneron’s Praluent® from a significant share
`
`of the PCSK9i market in order to ultimately eliminate this competition for Repatha® altogether.
`
`20.
`
`Amgen’s scheme has worked, and the results of Amgen’s unlawful exclusionary
`
`bundling are already substantial and will continue to grow worse. For example, at one Third-Party
`
`Payor, Praluent®’s share of PCSK9i sales has plummeted more than 60 percent in just six months.
`
`In aggregate, Praluent® has been substantially foreclosed from the PCSK9i market with no
`
`coverage from Third-Party Payors reimbursing 51 percent of prescriptions. As a result of
`
`Amgen’s anticompetitive practices, in 2022, Regeneron stands to lose money for the first time on
`
`the formerly profitable Praluent®. In 2020 and 2021, Regeneron took painful cost cutting measures
`
`
`
`
`9
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 10 of 103 PageID #: 10
`
`
`
`
`to eliminate its Praluent® sales force, stop future research and development for Praluent®, and
`
`significantly cut back its marketing and other expenses, in order to mitigate against Amgen’s
`
`practices. Put simply, there is nothing left to cut.
`
`21.
`
`But that is not all. At this significant level of restricted access, there are major
`
`spillover effects that will further harm Regeneron, because many physicians will simply prescribe
`
`the only product with widespread coverage. Amgen’s ability to leverage its much larger sales
`
`force across its portfolio of drug products to promote Repatha®, not to mention its willingness to
`
`use outright misrepresentation to steer prescribers away from Praluent®, therefore exacerbates
`
`these spillover effects. These compounding factors have already artificially limited Praluent®’s
`
`market access and will continue to cripple Regeneron’s ability to remain a viable competitor.
`
`Further, if Amgen’s unlawful anticompetitive tactics remain unrestrained by the law, potential new
`
`entrants will foresee their future foreclosure and refuse to invest (unless they are one of a few giant
`
`pharmaceutical firms or have products that would not compete as a prescription drug dispensed
`
`via pharmacies).
`
`22.
`
`The harm to competition, to Regeneron, and, especially, to patients resulting from
`
`Amgen’s unlawful anticompetitive behavior is significant. Because of Amgen’s exclusion of
`
`Praluent®, patients and physicians are deprived of choice in PCSK9 inhibitor treatments and
`
`competition is harmed by the diminution of competition and resultant higher prices for Repatha®
`
`in the long term. Regeneron accordingly files this suit to redress this unlawful anticompetitive
`
`behavior and harm to competition.
`
`PARTIES
`
`23.
`
`Plaintiff Regeneron is a corporation organized and existing under the laws of the
`
`State of New York with its principal place of business located at 777 Old Saw Mill River Road,
`
`Tarrytown, New York 10591. Regeneron is in the business of inventing, developing,
`
`
`
`
`10
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 11 of 103 PageID #: 11
`
`
`
`
`manufacturing, and marketing a variety of innovative pharmaceutical products. Regeneron
`
`markets and distributes Praluent® in the United States.
`
`24.
`
`Defendant Amgen is a corporation organized and existing under the laws of the
`
`State of Delaware with its principal place of business located at One Amgen Center Drive,
`
`Thousand Oaks, California 91320. Amgen markets and distributes Repatha®, Enbrel®, and
`
`Otezla® in the United States.
`
`JURISDICTION AND VENUE
`
`25.
`
`This Court has subject matter jurisdiction over all claims asserted against Defendant
`
`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.
`
`§ 26. This Court has supplemental jurisdiction over Plaintiff’s pendent state law claims pursuant
`
`to 28 U.S.C. § 1367.
`
`26.
`
`This Court has personal jurisdiction over Amgen under the U.S. Constitution and
`
`nationwide contacts under Section 12 of the Clayton Act, 15 U.S.C. § 22.
`
`27.
`
`Venue is proper in this District under Section 12 of the Clayton Act, 15 U.S.C. §
`
`22, and under 28 U.S.C. § 1391(b) and (c).
`
`28.
`
`For personal jurisdiction and venue purposes, Amgen may be found in or transacts
`
`business in this District, including through the marketing and sale of Repatha®, Enbrel®, and
`
`Otzela®. Amgen’s unlawful behavior was specifically intended to, has had, and will continue to
`
`have an anticompetitive effect and impact on Regeneron and U.S. consumers in this District, and
`
`elsewhere. Additionally, Amgen’s patent litigation campaign against Regeneron was pursued in
`
`this District, including the sought-after injunction that, in turn, Amgen’s sales representatives used
`
`to discourage physicians from prescribing Praluent® in favor of Repatha®.
`
`INTERSTATE COMMERCE
`
`29.
`
`The commercialization, development, manufacturing, marketing, sale, and
`
`
`
`
`11
`
`

`

`Case 1:22-cv-00697-UNA Document 1 Filed 05/27/22 Page 12 of 103 PageID #: 12
`
`
`
`
`distribution of Praluent®, Repatha®, Enbrel®, and Otezla® occurs in interstate commerce.
`
`FACTUAL BACKGROUND
`
`A.
`
`Treatment of High Low-Density Lipoprotein Cholesterol
`
`i.
`
`PCSK9 Inhibitors
`
`30.
`
`High systemic levels of LDL-C or “bad cholesterol” can lead to heart attacks,
`
`strokes, and cardiovascular disease. PCSK9 inhibitors eliminate LDL-C by leveraging the body’s
`
`natural way of removing LDL-C from the blood. In particular, LDL-C receptors, which are located
`
`on the surface of liver cells, are responsible for extracting LDL-C from the bloodstream. The
`
`PCSK9 protein, however, regulates this process by binding to and causing the degradation of these
`
`LDL-C receptors inside the liver cells. PCSK9 inhibitors prevent PCSK9 from binding to the
`
`LDL-C receptors, so the receptors are not degraded inside the cell. Therefore, the receptors can
`
`return to the cell surface and continue the body’s natural process of removing LDL-C from the
`
`bloodstream. See Amgen, 987 F.3d at 1082.
`
`31. While there are other FDA-approved treatments for lowering cholesterol, none is
`
`reasonably interchangeable with PCSK9 inhibitors. Doctors have historically treated high LDL-
`
`C levels with drugs called statins. In many cases, however, statins are not enough to bring a
`
`patient’s LDL-C to a healthy level and/or may not be tolerated by patients due to side effects. In
`
`those cases, PCSK9 inhibitors are critical. PCSK9 inhibitors therefore serve a unique patient
`
`population. Doctors typically prescribe only PCSK9 inhibitors for patients at a high risk for
`
`cardiovascular problems, such as individuals with familial hypercholesterolemia (“FH”), people
`
`at high risk who are unable to lower their cholesterol using other drugs, or people who are statin-
`
`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
`
`
`
`
`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

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket