Amgen v. Regeneron: Will the permanent injunction against Regeneron’s new PCSK9-inhibitor hold up on appeal?

By Zachary Silbersher
January 17, 2017

On January 5, 2017, the District of Delaware issued its long-awaited decision in the patent dispute pending between Amgen and Regeneron wherein the Court granted Amgen’s request for a permanent injunction against Regeneron’s new PCSK9-inhibitor cholesterol drug.

Both Amgen and Regeneron each independently spent billions of dollars over the past decade-plus developing a new class of cholesterol drug.  The drug itself comprises an antibody that binds to PCSK9 proteins.  The current thinking is that patients with high-risk cholesterol, i.e. those who do not respond to diet or life-style changes, suffer from high levels of “bad” cholesterol, known as “LDL.”  For those who do not have high-cholesterol, LDL is typically flushed from the body after it binds to LDL receptors that degrade it.  By contrast, patients with high-risk cholesterol have trouble degrading LDL, and thus suffer from higher LDL-levels.  The cause of high LDL levels is an excess of the protein PCSK9, which binds to LDL and its receptors.  That prevents the “bad” LCL from degrading and flushing from the body.  Amgen and Regeneron each developed a new class of PCSK9 inhibitor, which constitutes an antibody that binds to PCSK9 and bars it from binding to LDL and its receptors.  That, in turn, reduces excess LDL by allowing it to adequately degrade and flush from the body.

Amgen’s drug is call Repatha® and Regeneron’s drug is Praluent®.  The active ingredients in both Repatha and Praluent include specific antibodies that bind to PCSK9.  Both companies applied for and received FDA approval at roughly the same time.  Amgen applied for FDA approval in August 2014, and received approval in August 2015.  Regeneron applied for FDA approval in November 2014, but used an orphan drug priority review voucher to receive early approval in July 2015.  Thus, both drugs have been on the market since the summer of 2015.  Since then, the companies have been actively jockeying for market share in a nascent two-competitor market.

Whereas Regeneron managed to be the first to market, Amgen succeeded in getting to the Patent Office first.  Amgen originally sued Regeneron, along with Sanofi, its European partner, in October 2014.  Amgen asserted three patents directed to antibodies that bind to PCSK9.  Over the next month, Amgen commenced additional lawsuits as new patents issued from the Patent Office.  The cases were eventually consolidated, but Amgen eventually went to trial against Regeneron on only two of the originally asserted patents.

In February 2016, shortly before trial, Regeneron stipulated to infringement of the asserted patents.  The case went to trial in front of a jury in early March 2016 in the District of Delaware.  The primary issue before the jury was invalidity, and the jury returned a verdict in favor of Amgen.

After the jury verdict, the Court did not let the parties go to the jury on damages.  Rather, a couple weeks later, in late March 2016, the Court conducted a two-day bench hearing on whether or not Amgen is entitled to a permanent injunction of Regeneron’s Praluent drug.  At this time, Praluent had only been on the market for approximately six months, and the measure of past damages was immaterial next to the big prize that Amgen sought, namely, an injunction against its only competitor’s product.

At the injunction hearing, Regeneron stressed the differences between its drug, Praluent, and Amgen’s drug, Repatha.  Whereas Repatha is offered in a 140mg dose and 420mg dose, Praluent comes in lower doses, namely a low 75mg dose and a 150mg dose.  Regeneron emphasized that this difference is critical to whether an injunction should be granted.  Because Repatha does not offer a low dose formulation, Regeneron argued that Repatha generally lowers patients LDL levels as low as possible.  By contrast, Regeneron’s low-dose 75mg formulation allows doctors to titrate down a specific LDL target, without going as low as possible.  Amgen argued that there is no evidence that going as low as possible is unsafe.  But Regeneron soundly retorted that this is a new class of drugs, and there is simply insufficient long-term data on the risks of going as low as possible.  That, Regeneron emphasized, is a strong reason against granting an injunction because, for a health-related product, the public will greatly benefit from collecting long-term data on the risks and benefits of different dosage levels.

By contrast, Amgen argued that Regeneron essentially copied its drug.  It put on considerable evidence that the Regeneron was aware of its pending patent applications while developing Praluent.  Near the end of the second day, Amgen’s CEO suggested while testifying that its business model depends upon the possibility of enjoining competitors who are infringing its patents.  He suggested that, if Amgen had not secured patent protection for Repatha, it might not have pursued the drug.  In one of the Honorable Sue L. Robinson’s few substantive comments during the hearing, she questioned whether Amgen would have stopped pursuit of such a potentially profitable drug.  And she also suggested that Regeneron’s notice of Amgen’s pending patent applications, long before any claims issued, and long after it had already isolated its antibody, was egregious or improper conduct on Regeneron’s part.  She suggested that she sees two companies, one who made it to the market first (Regeneron) and one who made it to the Patent Office first (Amgen), and she was having trouble seeing either one with the higher moral ground.

Post-trial briefing closed in May 2016, and seven months later, on January 6, 2017, Judge Robinson issued a decision granting Amgen’s request for a permanent injunction of Regeneron’s Praluent.  Many of those following the case expected a long, detailed opinion with extensive findings of fact.  Instead, the opinion is a short seven pages that rather briefly runs through the four-factor eBay test: irreparable harm, adequacy of money damages, balance of hardships and public interest.

The opinion does not read as one with resounding confidence that Amgen is entitled to an injunction from a Judge who has taken considerable efforts to fortify her opinion against reversal on appeal.  On the contrary, it reads like a Judge wrestling with what is admittedly a very difficult and close decision as to whether an injunction is warranted.  Indeed, the opinion concedes that, “the court finds itself between and rock and a hard place.”  (Opinion at 6).  Further, the opinion concludes by voluntarily staying entry of the injunction for 30 days “to allow [Regeneron] the opportunity to appeal and request expedited review” from the Federal Circuit, or in the alternative, “to encourage the parties to reach an appropriate business resolution.”  (Opinion at 7).

Admittedly, this case presents a very difficult question on whether an injunction is warranted, and reasonable minds indisputably would have differed on application of the eBay factors.  The most difficult aspect of the opinion, and the one for which Judge Robinson found herself “between a rock and a hard place,” is that the consequence of this injunction deprives high-risk cholesterol patients of potentially life-saving or at least critical care.  There are only two currently approved PCSK9 inhibitors on the market, and evidence submitted at the injunction hearing demonstrated that certain populations of patients will inevitably be either immune or allergic to Amgen’s Repatha, leaving them theoretically without an alternative option.  There is no bright-line rule that health-related products must necessarily be more immune to being enjoined in the face of liability for patent infringement.  But that is precisely what one of the eBay factors asks about—namely, whether “the public interest would not be disserved by a permanent injunction.”  eBay Inc. v. MercExchange, LLC, 547 U.S. 388, 391 (2006).  Judge Robinson rightly observed that “the public interest of having a choice of drug should prevail.”  (Opinion at 6-7).

Despite this, Judge Robinson granted the injunction, which raises the inevitable question of Regeneron’s chances on appeal.  At the outset, the Federal Circuit reviews a decision granting a permanent injunction for an abuse of discretion, which creates a significant hurdle for Regeneron.  However, it is hard not to read Judge Robinson’s opinion as a soft hand-off, or even an invitation, for the Federal Circuit to weigh in on the ultimate question regarding the propriety of this injunction, and not simply address whether the Delaware Court, itself, abused its discretion.

Among the four eBay factors, Judge Robinson found that two of those factors (irreparable harm and remedies at law) weighed in favor of Amgen, one factor (balance of hardships) was neutral, and one factor (public interest) weighed in favor of Regeneron.  Without much analysis, the Court appears to conclude at the end of its opinion that because two factors weighed in favor of Amgen, and only one in favor of Regeneron, then the injunction is warranted.  Yet, what is the likelihood that the Court’s determination that any of these factors weighed for Amgen or Regeneron, respectively, was itself an abuse of discretion?

On irreparable harm, Judge Robinson focused on the nature of competition between the parties.  Amgen itself practices the asserted patents, it is a direct market competitor, there are only two competitors in the market, and the market itself is a nascent one where the only two competitors are actively establishing market share.  Given these circumstances, and what Judge Robinson described as “traditional evidence of loss of market share and momentum,” there was not likely an abuse of discretion that Amgen is being irreparably harmed.

Likewise, on balance of the hardships, Judge Robinson found that this factor is neutral because both parties expended billions of dollars to bring their respective drugs to market, and whether an injunction issues or not, one of the parties will suffer.  Similarly, on the public interest factor, it is not likely an abuse of discretion for Judge Robinson to have found that “taking an independently developed, helpful drug of the market does not benefit the public.”  (Opinion at 6).  While the Court held that it “will not substitute its judgment for that of the FDA, nor delve into weighing testimony on the propriety of treating patients with the 75 mg dose of Praluent (instead of the 150 mg dose or the 140 mg dose of Repatha,” the Court nevertheless found that the public interest factor weighs in favor of Regeneron, and thus against granting an injunction.

The one factor that may, however, be susceptible to a potential abuse of discretion is under remedies at law.  Judge Robinson found this factor weighed in favor of Amgen, but the Court’s reasoning for doing so is a bit more murky than the other factors.  Judge Robinson found that Amgen asserted that money damages will not suffice given that “patent protection is fundamental to [Amgen’s] business model and they will not be able to fully recoup their investment in Repatha without an injunction.”  (Opinion at 6).  Yet, that argument could be made in almost any patent case where the plaintiff is seeking an injunction.  Further, it is undisputed that Amgen can likely make a lot more money if an injunction is granted.  Yet, the publicly-available briefing does not outright support  Amgen’s position that it will not be able to recoup its investment in Repatha absent an injunction.  Rather, Amgen stated, “[w]ithout this patent right, Amgen would have not been able to protect its investment, generate adequate capital to re-invest in innovation-based R&D, or maintain the confidence of its investors.”  (Case No. 1:14-cv-01317-SLR)(Dkt. 40 at 20-21).  In fact, Amgen’s principle point appears to be that the public has a strong interest in a robust patent system.  (Id.).  That is undeniably true, but far different from proving that Amgen would not recoup its investment in Repatha, absent an injunction.  This is especially so given that, absent an injunction, Amgen will still presumably be able to recoup its investment through an ongoing royalty from Regeneron.

Judge Robinson also found that Amgen has suffered reputational harm.  Yet, again, the publicly-available evidence on this appears to be scant.  Amgen argued that it is suffering reputational harm do to “loss of innovator and first-in-class status.”  (Id. at 14).  Yet, both Amgen and Regeneron launched only one month apart, and the public is aware that Amgen filed its BLA first.  While Amgen claimed that its first-in-class status is being undermined by the presence of Praluent, its primary evidence for this was purported “inability to recruit and retain top talent, investors, and clinical investigators.”  (Id. at 9).  There were no surveys that doctors were frowning on Amgen’s PCSK9 drug, or other drugs, because it was beat to the market by one month by Regeneron.  All other things being equal, and given the public interest in a having a choice of drugs, is a company’s inability to recruit top talent and investors, sufficient to ban one drug from the market?

Importantly, the evidence of Amgen’s reputational harm and ability to recoup its investment may be critical to the outcome of Regeneron’s appeal.  Judge Robinson appears to have credited these points to Amgen, even though Regeneron may be able to successfully argue on appeal that the evidence does not support it.  If Regeneron can do that, then that may turn the appeal in Regeneron’s favor.  If the evidence for reputational harm was truly insufficient, that may turn the remedies at law factor in favor of Regeneron.  That, in turn, may mean that two factors weigh in favor of Regeneron, and only one in favor of Amgen.  And that may tip the appeal towards a reversal of the injunction.

This is undeniably a hard case and a close decision.  For such a big case, and such a big market for a new class of drugs, the outcome of this injunction still appears to hang in the balance.

The Author

Zachary Silbersher

Zachary Silbersher is a patent attorney located in New York City. He is a founding member of the patent law firm, Kroub Silbersher & Kolmykov PLLC as well as the patent-consultancy at Markman Advisors LLC. He can be reached at zsilbersher@kskiplaw.com.

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There are currently 1 Comment comments.

  1. Seth February 11, 2017 4:23 pm

    Great summary of this topic. Thank you.