Will Amarin’s new cardiovascular patent lawsuit against Hikma keep out generic sales?
Zachary Silbersher
The battle continues. We previously wrote about the Federal Circuit’s decision in the case (GlaxoSmithKline v. Teva) and how that case may offer Amarin another chance to bar generics from the market for Vascepa®. Sure enough, on November 30, Amarin filed suit against Hikma asserting three patents covering use of EPA to treat cardiovascular events. What are the takeaways from this suit?
Background
By way of background, Amarin previously sued Hikma in Nevada. That suit only asserted patents covering Vascepa®’s severe hypertriglyceridemia indication. In that prior suit, Amarin did not assert any patents covering its cardiovascular indication. That was because, when Hikma filed its ANDA for Vascepa®, Amarin had yet to receive approval for the cardiovascular indication and Hikma’s ANDA did not cover that indication.
When Amarin lost that suit, Hikma was only approved to market its generic for the hypertriglyceridemia indication. Hikma is nevertheless anticipated to benefit from off-label sales for the cardiovascular indication. Even though Amarin had separate patents covering its cardiovascular indication, it could not likely assert those patents against Hikma. That was based on existing precedent (e.g., Takeda Pharmaceuticals v. West-Ward) from the Federal Circuit that held generics cannot typically be liable for inducing infringement of method-of-use patents covering unapproved, off-label indications, even if the generic benefits from and is fully aware of those off-label sales.
The GlaxoSmithKline case changed that. It opened the door to make it easier for courts to find induced infringement of patents covering off-label generic sales. Thus, as we discussed in our earlier post, the GSK case raised the prospect that Amarin might sue the generics for Vascepa® with its REDUCE-IT patents.
That is what Amarin has done. In that sense, this is not a typical Hatch-Waxman case. Amarin has accused Hikma of infringing patents covering use of EPA for cardiovascular reasons even though Hikma does not appear to have filed an ANDA with the FDA for approval to sell its generic drug for the cardiovascular indication. Amarin has asserted three patents against Hikma: U.S. Patent Nos. 9,700,537; 8,642,077; and 10,568,861. The patents are each very different, but they each have claims covering use of pure EPA to reduce cardiovascular risk. There are few interesting aspects of this lawsuit.
Infringement
Amarin’s complaint against Hikma spends considerable time showing that Hikma specifically intends its generic formulation to be prescribed for cardiovascular reasons. Amarin does this by laying out different circumstantial evidence.
For instance, Amarin alleges that Hikma’s label removed a cardiovascular limitation from its label. Before Amarin added the cardiovascular indication to its label (following the REDUCE-IT study), the label included a statement that Vascepa®’s effect on certain cardiovascular events for patients with severe hypertriglyceridemia had not been studied. After Amarin added the cardiovascular indication to its label, it also removed the limitation statement. Yet, Amarin now alleges that, despite carving out the cardiovascular indication from its label and filing Section viii statements against Amarin’s cardiovascular patents, Hikma’s generic label nonetheless removed the cardiovascular limitation statement. (A generic typically files Section viii statements with the FDA with respect to patents covering a carved-out label, thereby informing the FDA these patents should not delay ANDA approval.) This, according to Amarin, shows Hikma’s intent to market its generic drug for the cardiovascular indication.
Amarin also highlights Hikma’s press releases announcing its generic formulation for Vascepa®. Amarin argues that these press releases implicitly telegraph to doctors that its generic formulation can be used for cardiovascular conditions. For instance, the press releases say that Hikma’s generic is “indicated, in part” for hypertriglyceridemia. They also quote approximately $1 billion in US sales for “all uses” of Vascepa®. They also do not specifically state that Hikma’s generic is not indicated for cardiovascular conditions. Amarin also alleges that Hikma’s website states that its generic drug is AB rated—meaning, determined to be therapeutically equivalent—for hypertriglyceridemia, which is broader than the specific condition approved in its label. Altogether, Amarin alleges this shows Hikma’s intent to encourage doctors to prescribe its generic drug for cardiovascular reasons.
This is all very compelling evidence, and but it is not a foregone conclusion that Amarin can prevail on its infringement theory. The GlaxoSmithKline case broke new ground, and it is extremely helpful to Amarin’s claims. Yet, when it comes to determining which facts support induced infringement for off-label uses, the court will be in somewhat unchartered waters. The facts of the GlaxoSmithKline provide guidance, but the facts of that case do not precisely mirror this case, and that will give Hikma room to distinguish. Given this, Hikma may choose to file a Rule 12(b)(6) motion to dismiss in response to Amarin’s complaint. That is relatively unusual move for a pharmaceutical patent case. But in this instance, Hikma may argue that—even assuming everything alleged in Amarin’s complaint is true—the facts don’t show induced infringement, either under GlaxoSmithKline case or any other case.
In an interesting twist that will surely be unique to this case, Amarin also points out that sometime in October, and presumably after the GlaxoSmithKline issued, Hikma removed many of these press releases from its website. Amarin’s suggestion is that, apprised of the new law on induced infringement for indication patents, Hikma attempted to cover its tracks. And doing so purportedly shows its intent to market the cardiovascular indication. While this may appear to be damning evidence, it also highlights that the relief available to Amarin from this case may not be a full injunction against Hikma’s generic drug. This is discussed in the next section.
Relief
Apart from challenging infringement, Hikma is likely to also attack the precise relief that Amarin is seeking. Amarin’s complaint specifically seeks an injunction against Hikma selling any drug infringing the asserted patents. In other words, Amarin wants Hikma’s drug to be taken off the market.
Yet, in the Nevada suit, there was no question that Hikma was seeking to sell its drug for the severe hypertriglyceridemia indication. If Hikma had lost that suit, it could not change its label to remove the hypertriglyceridemia indication altogether from the label in an effort to bypass the patents. By contrast, in this case, there is no dispute that Hikma has not received approval for the cardiovascular indication. Rather, the central dispute relates to Hikma’s marketing efforts—i.e., statements in press releases, statements on its website and so forth. Indeed, if Amarin proves infringement, it will be based primarily upon what Hikma is doing outside of its label.
Because of all that, Hikma is likely to argue that, even if it is proved to be an infringer, that does not warrant an injunction against Hikma selling its generic drug altogether. In lieu of that, Hikma could just stop saying and doing all the things that Amarin complains amounts to tacit marketing of the cardiovascular indication. In other words, Hikma can revise its press releases, revise its website, and add the cardiovascular limitation back into the label. And if it does, it will presumably no longer infringe.
Thus, Amarin’s chances of using this lawsuit to bar Hikma from the market altogether is doubtful. Indeed, Amarin’s principal goal from bringing this suit may be to force Hikma to revise its marketing, and thereby include explicit statements in its marketing materials—and perhaps in its label as well—that Hikma’s generic formulation is not indicated for cardiovascular events. If that dissuades some doctors from prescribing the generic off-label, and correspondingly preserves substantial sales for Amarin, then that is well-worth the cost of this lawsuit.
Taking this a step further, if this case settles, this is what a settlement may look like. In most Hatch-Waxman lawsuits that settle, the most material term is how long the generic will agree to delay entry into the market. But that is because the generic cannot typically design around the patent to avoid infringement. That is because infringement typically rises and falls based upon the wording of the label, and the FDA typically dictates the generic’s label must mirror the brand’s label. Here, however, Hikma can theoretically design around the patents by revising its activities outside of its label. And therefore, a settlement between the parties may boil down to an agreement over what Hikma can and cannot say about its generic drug.
There is also another form of relief available to Amarin that was unavailable in Nevada. That includes damages. Hikma’s generic has already launched. If Hikma’s sales are infringing, then Hikma owes Amarin damages. The principle way to calculate those damages would be Amarin’s lost profits. In theory, that could amount to a lot of money, and technically eclipse Hikma’s own profits. Yet, Hikma’s drug launched only a few weeks ago. Accordingly, the size of Amarin’s damages at this point are likely negligible. That said, this facet may put pressure on Hikma to settle. The longer the case drags on, the higher Hikma’s damages exposure becomes.
Invalidity
Even if Amarin can show infringement, to prevail in this lawsuit, it will have to face an invalidity challenge. The challenge will most likely focus on the JELIS study. That study purportedly suggested that purified EPA could reduce cardiovascular risks in patients with abnormal lipid levels who were on statin therapy.
During the prior Nevada lawsuit, the parties debated the relevance of the JELIS study. Amarin argued that the JELIS study was flawed, whereas the generics argued that Amarin had previously relied upon the JELIS study in its bid to the FDA for a cardiovascular indication Vascepa®. Either way, JELIS presents a validity challenge to the patents now asserted by Amarin, and this will likely form a focal point of the case.
Amarin appears to have contemplated this in selecting patents to assert against Hikma. One very interesting patent is the ‘537 patent. This is not a homegrown Amarin patent. Rather, this patent is owned by the Japanese company, Mochida Pharmaceutical, which is the manufacturer for Epadel, another EPA drug. (This is likely why Mochida is a plaintiff in this lawsuit.) Even though Amarin does not own this patent, it has an exclusive license, which permits it to bring suit.
The ‘537 patent has an earlier priority date than the other two asserted patents. During prosecution, the ‘537 patent also appears to have preliminarily overcome considerable prior art related to JELIS in the process of being granted by the Patent Office. Moreover, the patent is based upon the Saito article, which studied the use of EPA in patients enrolled in JELIS with no history of cardiovascular events. Therefore, the ‘537 patent is likely to be very important to this case.
Venue
Another interesting aspect of this new suit is that Amarin has brought it in Delaware. That is different from its last suit against Hikma, which was brought in Nevada. Unlike Nevada, Delaware is a popular district for patent pharmaceutical cases. The Judges in Delaware have generally presided over many more patent pharma cases that most other districts (apart from possibly New Jersey), and they are very familiar with the infringement and invalidity issues that typically arise in these cases.
There is nevertheless the possibility that Hikma (as well as Dr. Reddy’s, to the extent it is also sued) may move to transfer the case to Nevada. Hikma may also attempt to have the case should specifically assigned to the Honorable Miranda M. Du, who presided over the Nevada suit. These arguments in favor of transfer will not be easily dismissed. For one thing, Amarin previously sued Hikma in Nevada, and therefore, Amarin cannot likely argue it would be inconvenient for this suit to occur there. Moreover, Judge Du has already spent considerable time presiding over a case involving the same drug and similar patents, and is already very familiar with the facts that will overlap with that case—the REDUCE-IT study, the sales of Vascepa®, the history of the drug, and so forth. These are the types of arguments that often carry a transfer motion made by defendants.
On the other hand, this case has an unusual legal wrinkle that may save the case from being sent back to Nevada. When Amarin brought suit against Hikma and Dr. Reddy’s in Nevada, the law on patent venue was much broader. It has since been narrowed by the Supreme Court (in the TC Heartland case.) In addition, a very recent decision from the Federal Circuit further narrowed the available districts where generics can be sued in Hatch-Waxman cases. That means that when Amarin filed its recent suit against Hikma on November 30, Nevada was most likely not even a legal option. Motions to transfer typically fail if the plaintiff could not have legally filed in the requested district. This is therefore an unusual situation where an intervening change in the law of venue may mean that what would have otherwise been an easy transfer motion by Hikma under ordinary circumstances may no longer be so easy.
Whether Hikma decides to move to transfer is an issue worth watching. Yet, even if the case is transferred back to Nevada, and even if Judge Du presides over the case, there will be a big difference between this suit and the prior suit. Hikma has already launched its generic. Unlike the Nevada suit, that means that Hikma has sales, and Amarin has a claim to damages. Because there will be damages at stake, if this case goes to trial, it will most likely be tried in front of a jury, rather than the Judge as happened in Nevada. Trying cases to juries rather than Judges can be an entirely different affair.
Amarin has also not brought suit against Dr. Reddy’s. Thus, the existing suit against Hikma cannot address Dr. Reddy’s sales. Given that Dr. Reddy’s prevailed in the earlier Nevada suit, it has freedom to operate over the previously-asserted Marine patents. Thus, it is likely that Amarin will also bring a suit against Dr. Reddy’s for infringement of its cardiovascular patents.
That said, the suits may not necessarily parallel each other as in the prior Nevada suit. That is because infringement under the GlaxoSmithKline depends upon the individual marketing efforts of each generic. In the prior case, infringement essentially rose and fell based upon the wording of the generics’ prospective labels, and those labels were effectively the same. Now, however, to the extent Hikma and Dr. Reddy’s market their generic formulations differently, for instance by different wording in press releases and so forth, there is a universe where one generic could be deemed to infringe the patents, but not the other. For instance, as discussed above, Amarin alleges that after the GlaxoSmithKline decision issued, Hikma removed certain press releases from its website. This type of evidence may not be available in the case of Dr. Reddy’s.
The other wrinkle is that Amarin may not be able to sue Hikma and Dr. Reddy’s in the same court. Hikma is incorporated in Delaware, and has its headquarters in New Jersey, whereas Dr. Reddy’s is incorporated in New Jersey with its principal place of business also in New Jersey. Under the current venue rules for patent cases, that suggests that Dr. Reddy’s may not be amenable to suit in Delaware. Further, another recent Federal Circuit decision drastically narrowed where generics can be sued in Hatch-Waxman lawsuits. Together this suggests that the Hikma and Dr. Reddy’s suits may not be consolidated, with the Hikma suit in Delaware and Dr. Reddy’s suit in New Jersey.
The GlaxoSmithKline Case
Amarin’s new suit against Hikma hinges upon the GlaxoSmithKline case. Yet, as we discussed in our earlier blog post, it is not a foregone conclusion that that decision will remain intact. The case represented a relatively drastic change in the law, and there was a fierce dissent. While petitions for en banc review are typically denied, the GlaxoSmithKline case may be one of the exceptions where it is taken up by the Court. Teva’s deadline to file its petition for rehearing and en banc review is December 2, 2020. Thus, any handicapping of Amarin’s new suit against Hikma would be prudent to follow the GlaxoSmithKline appeal. Lots of moving pieces.