The Biologics Price Competition and Innovation Act of 2009 (BPCIA) was passed as part of health reform signed into law by President Obama in March 2010. This year, the BPCIA turns 10. While the U.S. Biosimilars Pathway has been slow to take shape, 26 biosimilars have now been approved (with 20 approvals in the past two years). This year we will see more litigation under the BPCIA, with biosimilar makers sharing or withholding information about their biosimilar products during the pre-suit BPCIA information exchanges, and continued disputes about what constitutes other manufacturing information under the statute and whether it will be disclosed. We will also see the continued onslaught of inter partes review (IPR) proceedings challenging patents protecting biologic medicines, including IPRs filed long prior to any litigation under the BPCIA. 2020 will also usher in some notable changes expanding the scope of products that are regulated and litigated under the BPCIA. It may also provide further guidance on circumstances requiring a 180-day notice of commercial marketing, biosimilar injunctions, interchangeability status and the impact of biosimilar settlements. Here is what’s ahead.
Biosimilar competition for certain biological products previously submitted under the Federal Food, Drug and Cosmetic Act (FD&C Act)
- The BPCIA requires a notable change as soon as it turns 10, resulting in the expansion of the number of medicines that are regulated under the BPCIA and therefore the expansion of the number of possible biosimilar products. In particular, after March 23, 2020, a marketing application for a biological product that historically could have been submitted under Section 505 of the FD&C Act (e.g., insulin and insulin analogs, human growth hormone, pancreatic enzymes, and reproductive hormones) will need to be submitted as a biologics license application (BLA) under Section 351 of the Public Health Service Act (PHS Act).
- Further, on March 23, 2020, a biological product previously approved under Section 505 of the FD&C Act will be deemed to be an approved BLA and regulated under the PHS Act. According to the Food and Drug Administration (FDA), “sponsors can seek approval of products that are biosimilar to, or interchangeable with, these transitioned products.”
Circumstances requiring a new notice of commercial marketing and biosimilar injunctions
- In Genentech’s appeals involving Amgen’s at-risk launch of biosimilar versions of Avastin and Herceptin, the Federal Circuit may provide further guidance on circumstances requiring a new 180-day notice of commercial marketing as well as guidance on biosimilar injunctions.
Avastin (bevacizumab)
- Amgen’s biosimilar for bevacizumab (Mvasi) was approved by the FDA in September 2017. In October 2017, Amgen served Genentech its notice of commercial marketing related to Mvasi. Amgen then filed two supplements to its BLA revising manufacturing and labeling information for its Mvasi product. These supplements were approved by the FDA in December 2018 and June 2019. Amgen did not provide any further notice of commercial marketing. On July 8, 2019, Amgen made a decision to launch Mvasi at risk. On July 10, 2019, Genentech filed a motion to enforce the BPCIA’s statutory prohibition on commercial marketing, as well as a temporary restraining order. Under the BPCIA, Amgen cannot market Mvasi until 180 days after Amgen provides Genentech notice of its intent to commercially market Mvasi. Genentech argued that Amgen’s October 2017 letter failed to satisfy the notice requirement because the Mvasi product approved in September 2017 was different from the products approved in December 2018 and June 2019. According to Genentech, new notices of commercial marketing were required as a result of Amgen’s two supplements to its BLA.
- On July 19, 2019, the district court denied Genentech’s motions, finding that Amgen’s October 2017 letter satisfied the notice requirements of subsection (l)(8)(A) of the BPCIA. The district court held that “under the express terms of the BPCIA, the same biologic product can be the subject of an application and supplements to the application.” The court also found that “the BPCIA’s language makes clear that a biologic product is not defined by its manufacturing facilities or labeling.” The district court denied Genentech’s request for a temporary restraining order on that basis.
Herceptin (trastuzumab)
- Amgen served Genentech its notice of commercial marketing related to its biosimilar for trastuzumab (Kanjinti) on May 15, 2018 (long prior to any approval). Over a year later (on July 10, 2019), and four weeks after Kanjinti was approved by the FDA, Genentech moved for a temporary restraining order and preliminary injunction to prevent Amgen from launching, marketing or selling Kanjinti until the district court rendered a decision on the merits and the Federal Circuit adjudicated any appeal.
- On July 18, 2019, the district court denied Genentech’s motions, finding that Genentech failed to show it would suffer irreparable harm absent an injunction. According to the opinion, Genentech filed its motion for a preliminary injunction 14 months after receiving the notice of commercial marketing, three months after receiving a specific launch date and approximately one month after Kanjinti was approved by the FDA. The court indicated that “Genentech’s actions are [ ] contrary to the spirit and purpose of the BPCIA” because the 180-day notice period is designed to prevent the circumstances that “Genetech has engineered in this case — ‘a race to court for immediate relief to avoid irreparable harm from market entry . . .’” The court further stated that Genentech’s undue delay in requesting a preliminary injunction should be sufficient by itself to deny the motion. However, the court held that a finding of no irreparable harm was also supported by the fact that “Genentech has engaged in a pattern and practice of licensing the Dosage Patents.”
- Genentech appealed both adverse decisions to the Federal Circuit and moved for injunctions pending appeal. In August 2019, the Federal Circuit denied Genentech’s motions for an injunction pending appeal in both cases, stating that “[w]ithout prejudicing the ultimate disposition of this case, we conclude that Genentech has not established that an injunction pending appeal is warranted here under these factors.”
Interchangeability status for biosimilar products
- On May 10, 2019, the FDA provided final guidance on interchangeability, clarifying how sponsors may demonstrate a biosimilar product is interchangeable with a branded biologic medicine. The interchangeability designation for a biosimilar product allows for its substitution at the pharmacy without the involvement of the prescriber, similar to how generic drugs may be substituted for branded drugs.
- Thus far, there have been no interchangeable biosimilars approved in the United States. However, for the past two years, Boehringer Ingelheim has been conducting interchangeability studies for a biosimilar to AbbVie’s Humira. 2020 may provide more guidance on the requirements for interchangeability.
Antitrust litigations impacting biosimilars and biologics
- On March 18, 2019, an antitrust class action lawsuit was filed by a welfare fund against AbbVie and seven biosimilar companies involving the drug adalimumab (Humira). The complaint alleges that AbbVie and the biosimilar competitors entered into “unlawful market division agreements” which allowed competition in Europe but “which delay biosimilars in the U.S. market until at least January 2023.” AbbVie’s briefing in support of its motion to dismiss contends that the plaintiffs’ suit seeks to “usher in the end of any international early-entry patent settlement unless it provides for the same world-wide entry date; and chill medical and therapeutic innovation.” Opposition and reply briefs to the motion to dismiss were filed in November 2019, and December 2019, respectively.