Supreme Court Takes Up Hikma v. Amarin: A Pivotal Test for Skinny Labeling

Legal background

The sponsor of a new drug application (NDA) is required to list patents that claim the active ingredient, drug product, and approved methods of use for its product in the Orange Book. 21 USC 355(b)(1)(A)(viii). In turn, the sponsor of an abbreviated new drug application (ANDA) for a generic product must either certify to the patents listed for the reference listed drug (RLD) or “carve out” patented methods of use from its drug labeling. 21 USC 355(j)(2)(A)(vii)–(viii). The submission of a paragraph IV certification challenging the patent as invalid or not infringed is a technical act of patent infringement that can lead to litigation and a related 30-month stay of approval. In contrast, skinny labeling that omits the patented method of use generally may allow the generic applicant to avoid litigation and the 30-month stay. FDA may approve skinny labeling only when the proposed omissions “do not render the proposed drug less safe or effective than the listed drug for all remaining, non-protected conditions of use.” 21 CFR 314.127(a)(7).

There are situations, however, when FDA-approved skinny labeling does not safeguard the generic sponsor from claims of induced patent infringement. 35 USC 271(b). To establish such a claim, a plaintiff must prove three elements: 1) that the defendant “actively” induced infringement, 2) that the defendant knew its acts would induce infringement, and 3) that the induced use constitutes direct patent infringement. 

Administrative background

Hikma v. Amarin concerns the RLD, Vascepa (icosapent ethyl). The product was initially approved in 2012 “as an adjunct to diet to reduce triglyceride (TG) levels in adult persons with severe (≥500 mg/dL) hypertriglyceridemia” (the SH indication). The labeling also contained a limitation of use: “The effect of VASCEPA on cardiovascular mortality and morbidity in patients with severe hypertriglyceridemia has not been determined.” In 2019, following additional clinical testing, Vascepa was approved as a treatment to reduce cardiovascular risk in patients with blood triglyceride levels of at least 150 mg/dL (the CV indication). Amarin contemporaneously removed the limitation of use from Vascepa's labeling. Patents for both methods of use were listed in the Orange Book.

In 2016, Hikma submitted an ANDA for a generic version of Vascepa. At that time, Vascepa was approved for the SH indication, but not the CV indication. In its submission, Hikma certified that the applicable SH patent was invalid, ultimately prevailing on this claim in district court. In 2019, following Vascepa's approval for the CV indication, Hikma filed a Section VIII statement declaring it would carve out the patented method of use. Although it sought approval for only the SH condition of use, and not the CV indication, the Hikma skinny labeling did not include a limitation of use for cardiovascular treatment. FDA approved the Hikma generic in 2020. 

Alleged infringement by Hikma

After the ANDA approval, Amarin sued Hikma for induced infringement of the patent directed to the CV indication.  The alleged acts of induced infringement by Hikma fall into three categories: 1) the labeling, 2) statements made in press releases, and 3) the Hikma website. Hikma did not make direct mention of the CV indication on the labeling of its product. However, it failed to include the cardiovascular limitation of use, and at the same time included information in the Warnings and Precautions section noting increased likelihood of atrial fibrillation or atrial flutter in patients with cardiovascular risk factors. Furthermore, in the Clinical Studies section, the labeling described a trial of statin-treated patients with the same cardiovascular history and lipid levels covered by the asserted patents. In other words, the labeling contained information inclusive of the population to be treated by the claimed CV method of use.

In its marketing material, Hikma often referred to its product as the “generic version of Vascepa®.” The company failed, however, to note that its product was not indicated for all the approved uses of Vascepa. In fact, when describing Vascepa, Hikma stated it was “indicated, in part, [to treat] severe (≥500 mg/dL) hypertriglyceridemia” (emphasis added). As explained by Amarin, this had the effect of saying that the generic can be used more broadly than its SH indication, bleeding over into the “carved-out” CV condition of use. Additionally, Hikma frequently referred to Vascepa sales figures when trying to secure new investors, failing to distinguish whether the profits derived from the SH or CV indication. 

Finally, the Hikma website described the generic product as being in the “Therapeutic Category: Hypertriglyceridemia.” This category, Amarin argued, is inclusive of infringing uses. The website was notably distinct from Hikma's advertising: it indicated the product is only “AB” rated and made clear that “Hikma's generic version is indicated for fewer than all approved indications of the Reference Listed Drug.” 

The district court dismissed the claim of induced infringement, finding that the CV information in Hikma's labeling (and the absence of the limitation of use) did not result in induced infringement and that the press statements and website similarly did not rise to an actionable level.  The Federal Circuit reversed. Like the district court, it explained that the labeling, in-and-of-itself, was not sufficient to state a claim. However, considered in combination with statements made in the press and on Hikma's website, the Federal Circuit concluded the case should proceed to trial. 

Petition for certiorari and brief of the Solicitor General

In its petition for a writ of certiorari, Hikma raised two issues. First, “[w]hen a generic drug label fully carves out a patented use,” whether reference to a product as a “generic version” of the RLD and citation to public information about the RLD (e.g., sales) is sufficient to state a claim of induced infringement. Second, the Court was asked whether a claim of induced infringement can exist without an alleged instruction or statement that “encourages, or even mentions, the patented use.” 

In a largely policy-oriented brief, the Solicitor General urged the Court to hear the case. The Solicitor General opined that, if the opinion of the Federal Circuit is upheld, the very purpose of the generic approval pathway would be upset: by affording fewer protections to generic manufacturers, there will also be less incentive for sponsors to develop low-cost alternative treatments.  

Looking ahead

This case comes before the Supreme Court on a motion to dismiss for failure to state a claim. The Court is not deciding whether Hikma actually induced infringement, which is an issue for trial. Instead, its ruling will determine only whether the case can move forward.

That, however, does not diminish the importance of the Supreme Court's decision to hear the case, and the potential consequences of its ultimate holdings. If the Court upholds the Federal Circuit, generic manufacturers may be more limited in the way they can market their products. However, a ruling in favor of Hikma will make it more difficult to sustain a claim of induced infringement when the allegations involve “off-label” use of the generic for the carved-out condition of use.

We will continue to keep you informed about developments in this case and the carve-out regulations more generally. If you have any questions regarding how this litigation may impact your products, you may contact any of the authors of this alert or the Hogan Lovells attorney with whom you regularly work. 

Authored by Gary Veron, Jason Conaty, and Noah Fisher