On January 4, 2022, the District Court for the District of Delaware granted Hikma Pharmaceuticals USA Inc.’s (“Hikma”) motion to dismiss Amarin Pharma Inc.’s (“Amarin”) infringement claims, finding that Hikma’s “skinny label” for its generic heart drug, icosapent ethyl, did not induce infringement of Amarin’s three patents. This decision comes on the heels of the Federal Circuit’s recent decision in GlaxoSmithKline LLC v. Teva Pharms. USA, Inc., 7 F.4th 1320, 1338 (Fed. Cir. 2021) and is a victory for generic manufacturers who raised concerns about the future of the generic industry and the use of “skinny labels.”

State of Federal Circuit Law on “Skinny Labels”

As we have previously reported, the generics industry has been concerned with infringement liability for selling drugs with labels that carve out patented uses (aka “skinny labels”) after the Federal Circuit twice ruled in favor of GlaxoSmithKline (“GSK”) in their case against Teva Pharmaceuticals. USA (“Teva”). First, in October of 2020, the Federal Circuit found that substantial evidence, i.e. Teva’s marketing of its drug as equivalent to the brand drug and physicians’ knowledge that brand drug could be used to treat the indication, supported the jury’s finding that Teva was liable for induced infringement for the patented indication it carved out of its skinny label. However, the Federal Circuit’s opinion left several questions unanswered and raised several concerns about whether listing a generic drug as AB-rated meaning that it is therapeutically equivalent (displaying bioequivalence and pharmaceutical equivalence) to a brand drug could establish inducement and whether ANDA filers that carve out patented uses under section viii of 21 U.S.C. § 355(j)(2)(A) could be liable for infringement. After Teva filed a petition for rehearing which was supported by seven amicus curiae briefs, the original panel vacated its October 2020 ruling and decided to rehear the case entirely.

In August of 2021, after another round of oral arguments, the panel again affirmed the jury’s findings that Teva’s “partial label” induced infringement of GSK’s patent. The Federal Circuit held that substantial evidence demonstrated that “Teva’s partial label did not successfully carve out the patented use, and thus, Teva was selling its generic with a label which infringed the method claim.”[1] Accordingly, Teva’s label was “not a skinny label.”[2] The Federal Circuit also held that Teva’s marketing materials encouraged physicians to prescribe carvedilol in a manner that would cause infringement.[3] In its decision, the panel stated that the laws regarding generic drugs remain intact and quoted the language of an amicus brief to explain the law as follows:

“Generics could be held liable for actively inducing infringement if they marketed a drug with a label describing a patented therapeutic use or if they took active steps to encourage doctors or patients to use the drug in an infringing manner. But generics could not be held liable for merely marketing and selling under a ‘skinny’ label omitting all patented indications, or for merely noting (without mentioning any infringing uses) that FDA had rated a product as therapeutically equivalent to a brand-name drug.”[4]

The Federal Circuit clarified that its holding was a “narrow, case-specific review” and “does not upset the careful balance struck by the Hatch-Waxman Act regarding section viii carve-outs.”[5] According to the Federal Circuit, Teva did not omit all patented indications or note (without mentioning any infringing uses) that the FDA found a product therapeutically equivalent to a brand product.[6] On October 7, 2021, Teva filed a Petition for Rehearing en banc. In its Petition, Teva argues that “[t]he panel’s decision contradicts settled precedent, eviscerates the carve-out statute, and throws inducement doctrine into disarray.” [7] Quoting Judge Prost’s dissent, Teva argues that “[b]ecause ‘the background facts here will seemingly persist in most skinny-label cases,’ the effects of the decision will be seismic.” [8]

After this decision, many generic companies raised concerns about whether this opinion materially altered the “skinny label” regime or at the very least removed it as a viable option for FDA approval.[9]

Aside from raising generic’s concerns, the Federal Circuit panel’s opinion in GlaxoSmithKline LLC v. Teva Pharms. USA, Inc. also raises the appearance of a split in Federal Circuit law on inducement of “skinny labels.” For example, previously, in Grünenthal GMBH v. Alkem Labs Ltd., 919 F.3d 1333, 1339-40 (Fed. Cir. 2019), a different panel affirmed the district court’s finding that the defendants’ “skinny labels” did not induce infringement band because neither label was specifically indicated for the patented treatment, or made a reference to the patented indication. The panel found that even though the label was indicated for “[m]oderate to severe chronic pain,” which included both infringing and non-infringing uses, it did “not specifically encourage use” of the generic for the patented “treatment of polyneuropathic pain.” [10] Grünenthal differs from the GSK case in that it did not involve statements by the generic regarding the equivalency of its drug to the branded drug. However, the panels’ competing views on inducement demonstrate a clear split and one that will continue to create uncertainty and concerns for the lower courts until its resolution.

Amarin Pharma, Inc. v. Hikma Pharms. USA, Inc.

The most recent decision addressing these concerns came on January 4, 2022. In Amarin Pharma, Inc. v. Hikma Pharms. USA, Inc., No. 20-1630 (D. Del.), Judge Richard G. Andrews of Delaware issued an opinion dismissing Amarin’s induced infringement claims against Hikma. The three patents-at-issue in the litigation relate to methods of using icosapent ethyl for the reduction of cardiovascular risk. Amarin sued Hikman, alleging that Hikma had induced doctors to infringe the patents by encouraging them to prescribe the generic for patent protected indications. Amarin also sued Health Net, LLC (“Health Net”), alleging that its formulary placement induces infringement by encouraging Hikma’s generic for the patented use.

Amarin’s brand product, Vascepa® (icosapent ethyl), is used in the treatment of hypertriglyceridemia and cardiovascular risk reduction. Amarin’s patents only cover using icosapent ethyl to treat cardiovascular risk reduction. Hikma had received FDA approval to sell its generic version of icosapent ethyl for use in the non-patented indication of hypertriglyceridemia under the “skinny label” regime. Amarin argued that the label used by Hikma to sell its generic was “not-skinny-enough” and that this label combined with Hikma’s public statements resulted in induced infringement of the patented indication[11]. Specifically, Amarin asserted that Hikma’s label teaches cardiovascular risk reduction because it contains a warning for patients with cardiovascular disease and it does not explicitly state that the product should not be used for the patented indication.

Judge Andrews disagreed with Amarin and found that neither Hikma’s label nor its statements teach using the generic in cardiovascular risk reduction. As to the label, Judge Andrews held that the notice regarding side effects is a warning and not an instruction to use icosapent ethyl to reduce cardiovascular risk. Relying on Takeda Pharms. U S.A., Inc. v. W-Ward Pharm. Corp., 785 F.3d 625, 632 n.4 (Fed. Cir. 2015), Judge Andrews also found that the label’s silence regarding cardiovascular risk reduction does not plausibly amount to inducement because generic labels do not need to contain a statement discouraging use of the patented indication.[12] Judge Andrews further found that Hikma’s press releases and website did not support accusations of actual induced infringement. The fact that Hikma’s press releases described icosapent ethyl as the “generic equivalent” of Vascepa® was not sufficient to establish inducement. With respect to the website, Judge Andrews relied on Grünenthal GMBH v. Alkem Labs Ltd., 919 F.3d 1333, 1339-40 (Fed. Cir. 2019), and held that without more, the mere fact that Hikma advertises its product as “AB rated” in a therapeutic category that includes both patented and non-patented uses does not amount to specifically encouraging use for the patented treatment.[13] In light of these facts, Judge Andrew granted Hikma’s motion to dismiss.

By contrast, Judge Andrews denied Health Net’s motion to dismiss the induced infringement claims. Judge Andrews found that formulary selection and the prior authorization process could amount to affirmative acts of induced infringement. Judge Andrews found that “Health Net’s prior authorization form supports an inference of specific intent because it lists the patented indication on the generic icosapent ethyl capsules form” and that its “placement of generic icosapent ethyl on a preferred tier encourages the substitution of the generic for the branded drug, including for the patented indication.”[14] Ultimately, Judge Andrews agreed with the recommendations of the Magistrate Judge that Amarin had pled enough to survive the motion to dismiss stage.

Conclusions

The decision in favor of Hikma provides some reassurance to generic companies that the “skinny label” regime remains alive and well and that the Federal Circuit’s decision in GlaxoSmithKline LLC v. Teva Pharms. USA, Inc., was narrowly tailored to a specific set of facts.

However, the conversation continues as to the future of skinny-labeled generics and whether the language of press releases, web pages and other marketing materials requires more scrutiny. Additionally, the liability of insurance companies is coming into the spotlight. Amarin was able to defeat the motion to dismiss filed by Health Net, which suggests that we may see more cases against insurance companies in the future. It will be interesting to see whether other brand companies target not only insurers, but other companies in the supply network.

We will continue to provide updates on the evolving skinny-label landscape including the Federal Circuit’s decision on Teva’s en banc petition as well as any appeals of the Amarin decision.

[1] GlaxoSmithKline LLC v. Teva Pharms. USA, Inc., 7 F.4th 1320, 1338 (Fed. Cir. 2021).

[2] Id. at 1328.

[3] Id. at 1336-38.

[4] Id. at 1326.

[5] Id.

[6] Id.

[7] GlaxoSmithKline LLC v. Teva Pharms. USA, Inc., No. 18-1976, Dkt. 195 at 10 (Fed. Cir. Oct. 7, 2021).

[8] Id.

[9] See GlaxoSmithKline LLC v. Teva Pharms. USA, Inc., No. 18-1976, Dkt. 213 (Fed. Cir. Oct. 25, 2021) (Amicus Brief of Apotex, Inc.); see also Dkt. 217 (Amicus Brief of Mylan Pharmaceuticals Inc.).

[10] Id.

[11] Amarin Pharma, Inc. et al v. Hikma Pharms. USA Inc., No. 20-1630, slip op. at 6-7 (D. Del. Jan. 4, 2022).

[12] Id. at 7.

[13] Id. at 9.

[14] Id. at 11.