This summer, the U.S. District Court for the District of Delaware faced a question of first impression in the Genentech Inc. v. Amgen Inc. bevacizumab biosimilar litigation: Does the FDA’s approval of a supplement to an already-approved biosimilar application trigger an obligation by the applicant to provide a new notice of commercial marketing (NCM)?
On July 18, the district court ruled that Amgen was not required to provide a new NCM to Genentech in this situation, and that Amgen’s earlier, pre-supplement NCM remained effective. The district court’s decision cleared the way for Amgen to immediately launch MVASI® (bevacizumab-awws) as the first biosimilar of AVASTIN® on the market in the U.S.
The decision, now on appeal, is notable for presenting the first major legal dispute regarding NCM since the Supreme Court decided the seminal case concerning this provision, Sandoz v. Amgen, in 2017.
This article examines the district court’s decision in view of established NCM jurisprudence, and identifies yet-unanswered questions regarding NCM that may or may not be addressed by the Federal Circuit on appeal.
The NCM provision, subsection (l)(8)(A) of the Biologics Price Competition and Innovation Act (BPCIA), states that the “subsection (k) applicant shall provide notice to the reference product sponsor not later than 180 days before the date of the first commercial marketing of the biological product licensed under subsection (k).”
This provision acts as a gateway that gives the reference product sponsor the opportunity to enforce its patent rights, such as by seeking a preliminary injunction, to protect its market position from imminent biosimilar competition.
Until recently, controversy surrounded the fundamental issue of when an applicant may first provide NCM. In 2015, the Federal Circuit held in Amgen v. Sandoz (concerning Sandoz’s filgrastim biosimilar) that an applicant can provide NCM only after the FDA approves the biosimilar application.
A year later, in Amgen v. Apotex (concerning Apotex’s proposed pegfilgrastim biosimilar), the Federal Circuit relied on its 2015 Sandoz decision to conclude that subsection (l)(8)(A)’s “requirement of 180 days’ post-licensure notice before commercial marketing … is a mandatory one enforceable by injunction.”
These rulings would have effectively handed reference product sponsors six additional months of exclusivity from biosimilar competition beyond the statutory 12 years granted to new biologic products. This Federal Circuit precedent, however, was short-lived.
In 2017, the Supreme Court took up the 2015 Sandoz decision (but declined to review the 2016 Apotex decision) and held that a biosimilar applicant can provide NCM even before FDA-approval—a reversal of the Federal Circuit. For the next couple of years, few if any disputes arose regarding the legal aspects of providing NCM.
A Question of First Impression
In July, however, Genentech sought to block Amgen from launching its MVASI® biosimilar with a motion “to enforce the statutory prohibition on commercial marketing” (essentially, a preliminary injunction motion), together with a motion for a temporary restraining order. Genentech argued that although Amgen had already provided NCM in 2017, Amgen was required to provide a new NCM and wait another 180 days before marketing MVASI® because Amgen had submitted supplements to its aBLA that changed manufacturing and labeling information for the biosimilar product.
FDA’s approval of the supplements, according to Genentech, meant that the MVASI® biosimilar for which Amgen had originally provided NCM was actually a different “biological product” under the BPCIA than the MVASI® biosimilar that Amgen was seeking to imminently launch. Genentech therefore contended that this different “biological product” required a new NCM.
On July 18, the district court denied Genentech’s motions. In so ruling, the court held that the BPCIA’s express terms show that the same “biological product” can be the subject of a biosimilar application and supplements to that application. In short, the original and supplemental MVASI® approvals concerned the same “biological product.” The court therefore concluded that Amgen’s original NCM in 2017 remained legally effective and a new NCM was unnecessary.
Immediately after the decision, Amgen launched MVASI® and, within a day, Genentech appealed to the Federal Circuit.
Questions That May Be Addressed on Appeal
The Federal Circuit has yet to address several questions relating to the BPCIA’s NCM provision.
1. Does FDA-approval of a supplement ever obligate the biosimilar applicant to issue a new NCM?
Genentech argued in its motion that the approved amendments to Amgen’s MVASI® application were “major changes” that may implicate new patent rights or the parties’ ongoing BPCIA litigation. Thus, Genentech argued, the supplements’ approvals obligated Amgen to engage in a new patent dance and provide a distinct NCM relating to the post-supplement biosimilar product.
Although the district court denied Genentech’s motion, it did not assess the significance of Amgen’s supplements beyond acknowledging Genentech’s characterization of them as “major.” Instead, the court found that whether a single biological product has been licensed more than once is “irrelevant” to compliance with subsection (l)(8)(A).
On appeal, the Federal Circuit might rule only on the specific facts of the case, or it could issue dicta regarding circumstances under which a new NCM might be required.
2. Is Subsection (l)(8)(A) enforceable by injunction?
Although Genentech has argued to the courts that compliance with subsection (l)(8)(A) is enforceable by injunction, and Amgen has not objected, no appellate court has ruled on this issue since the 2017 Sandoz opinion. The Supreme Court in Sandoz did not directly decide this issue, but held that a different section of the BPCIA, subsection (l)(2)(A) governing the “patent dance” procedures, is not enforceable by injunction. The logic of the Supreme Court’s reasoning with regard to non-compliance with subsection (l)(2)(A) may apply equally in the context of non-compliance with subsection (l)(8)(A).
Thus, one question that the Federal Circuit may address on appeal is whether Genentech even had a legal basis to seek to compel Amgen to comply with subsection (l)(8)(A) in its preliminary injunction motion.
3. What remedies are available to a sponsor if an applicant launches a biosimilar product less than 180 days after providing NCM?
This circumstance is not present in Genentech v. Amgen and does not appear to have occurred before. But the question remains how the BPCIA would operate in this scenario, including what repercussions, if any, an applicant might face for an early launch.
For instance, if the launch were near the end of the 180-day period, there might be insufficient time for the reference product sponsor to seek emergency injunctive relief. If the launch were to come earlier in the 180-day period, the answer may depend on whether compliance with subsection (l)(8)(A) is enforceable by injunction, as discussed above. Still, given that these are uncharted waters, a biosimilar applicant might be wary of potential risks from launching before 180 days expire, for example, in terms of damages, permanent injunctive relief, or coloring the litigation in an unconstructive way.
Even after the Supreme Court’s Sandoz decision, many open questions remain about how many of the provisions of the BPCIA operate. To date, there have been fewer than 30 BPCIA litigations (many of which settled before adjudication) and only nine U.S. biosimilar launches, so relatively few opportunities have arisen to test and resolve these questions.
As demonstrated by Genentech v. Amgen, there is likely a great deal of case law yet to be written on this topic.
This column does not necessarily reflect the opinion of The Bureau of National Affairs, Inc. or its owners.
Joshua Whitehill is a counsel in Goodwin’s Intellectual Property Litigation group, where he focuses his practice on patent matters in the area of pharmaceuticals and other life sciences. He has represented clients in federal district and appellate courts, patent office proceedings, and arbitration in patent and license disputes relating to small molecule and biologic products, diagnostic methods, and genetic engineering.
Alexandra Valenti is a partner in Goodwin’s Intellectual Property Litigation group, focusing her practice on patent matters across a variety of industries, including pharmaceuticals, biotech, consumer products, and computing. She has represented clients in patent infringement lawsuits in federal courts nationwide, including significant victories after trial and on appeal, and represents clients in intellectual property matters outside of litigation, including in licensing disputes and arbitrations.