It was a remarkable year in many respects for the maturing US biosimilars field, with new launches and approvals and new legal issues explored, found life sciences attorneys Geoff Biegler and Jenny Shmuel.
Regulatory agencies and legislators also renewed their focus on access to lower-cost biologics, including biosimilars, said the Fish & Richardson principals during a webinar reviewing developments in the US biosimilars field.
“Among other efforts, FDA announced several initiatives to facilitate biosimilar development. Regulatory agencies also addressed biologic drug pricing and anti-competitive behavior in the biosimilars space.”
The Fish & Richardson webinar summary details all the legislation and regulatory developments that occurred in 2022 supporting US biosimilar market development.
While US Food and Drug Administration (FDA) approvals slowed significantly during the height of the global COVID-19 pandemic, they rebounded in 2022, with seven new biosimilar approvals, they noted. All of those, however, referenced products with previously approved biosimilars; there were no biosimilars approved in 2022 referencing new reference products.
The agency also designated two new interchangeable biosimilars last year: Rezvoglar, referencing Lantus (insulin glargine) and Cimerli, referencing Lucentis (ranibizumab), doubling the number of FDA-approved biosimilar products with an interchangeability designation, bringing the total number to four, said the attorneys.
The number of development programs enrolled in FDA’s Biosimilar Biological Product Development Program—FDA’s program for expediting the process for the review of submissions in connection with biosimilar biological product development—has risen again. As of Q4 of fiscal year 2022, the agency reported 106 programs participating in the scheme.
In addition, more biosimilar product developers have initiated studies to support interchangeability or submitted applications to FDA seeking interchangeability status, reported the legal experts.
“For example, both Alvotech and Pfizer have announced that FDA accepted interchangeability applications for their respective Humira biosimilars, AVT02 and Abrilada. Celltrion has announced that it will pursue a Phase III clinical trial to support interchangeability of its Humira biosimilar, Yuflyma, and Samsung Bioepis and Amgen have announced that they will pursue interchangeability designations for their Humira biosimilars, Hadlima and Amjevita, respectively.”
With more FDA-approved interchangeable biosimilars in the pipeline, federal lawmakers have begun introducing new legislation aimed at improving patient access to cost-saving biosimilars by removing barriers to substitution and increasing public trust in interchangeable biosimilars, said the Fish & Richardson duo. "While this legislation was not enacted by the 117th Congress, it provides insight into those issues that may be the focus of future legislation."
Four new Biologics Price Competition and Innovation Act (BPCIA) cases were filed in 2022. Those legal proceedings make up all the ongoing BPCIA litigation, as all of the cases filed prior to 2022 have been resolved, reported the legal team.
In 2022, new lawsuits were filed for more recent reference products, including, Tysabri (first FDA-approved in 2004), Stelara (first FDA-approved in 2009), and Eylea (first FDA-approved in 2011). “These newer reference products have introduced new issues in BPCIA litigation.”
The webinar reviewed the status of each new BPCIA case:
Genentech versus Tanvex
This case involves Tanvex’s proposed biosimilar of Genentech’s Herceptin (trastuzumab) called TX05. Tanvex is the fifth trastuzumab biosimilar developer against which Genentech has brought BPCIA litigation, following litigation against Pfizer, Celltrion/Teva, Amgen, and Samsung Bioepis, all of which settled between 2018 and 2020. In 2017, Genentech also reached a settlement with Mylan in relation to Genentech’s patents for trastuzumab, in which Mylan agreed to withdraw two inter parties review challenges. Each of these companies has commercially launched its trastuzumab biosimilar in the US.
The parties have notified the court that they had reached an agreement-in-principle to resolve their claims and expected to file a joint stipulation to dismiss sometime in January or early February 2023
Regeneron versus Mylan
On August 2, 2022, Regeneron filed a complaint against Mylan asserting infringement of 24 patents. The case relates to Mylan’s Eylea (aflibercept) biosimilar called M710. This is the first BPCIA litigation filed in the Northern District of West Virginia, the first BPCIA litigation involving Regeneron, and the first BPCIA litigation involving a proposed biosimilar of Eylea (aflibercept). "Eylea (first FDA-approved in 2011) is the newest biologic to be subject to BPCIA litigation, raising issues of first impression for the courts."
A Markman hearing is scheduled for January 24, 2023, and a trial is scheduled for June 12, 2023
Biogen versus Sandoz and Polpharma
Biogen filed a sealed complaint against Sandoz and Polpharma on September 9, 2022, related to the defendants’ Tysabri (natalizumab) biosimilar PB006. Biogen’s complaint asserted 28 patents relating to natalizumab and associated manufacturing and testing methods. "This is the first BPCIA litigation involving Biogen as the reference product sponsor, the first BPCIA litigation involving Polpharma, and the first BPCIA litigation involving a proposed biosimilar of Tysabri (natalizumab)."
On October 14, 2022, Biogen and Sandoz filed a joint stipulation and scheduling order for expedited preliminary injunction proceedings. Briefing on Biogen’s motion for preliminary injunction is scheduled to be completed by April 2023, and a preliminary injunction hearing is to be scheduled thereafter.
Janssen versus Amgen
Janssen filed a complaint against Amgen on November 29, 2022, alleging infringement of US patents ’734, which covers ustekinumab, and ’307, which covers methods of treating ulcerative colitis with ustekinumab. "This is the first BPCIA litigation involving a proposed biosimilar of Stelara (ustekinumab)."
On December 20, 2022, the parties filed a joint stipulation to extend the deadline for Amgen to move, answer, or otherwise respond to the complaint through and including January 23, 2023. On the same day, the court ordered the extension.
On the horizon
The next 12 months are poised to bring even more developments, with 10 or more Humira (adalimumab) biosimilar companies having settled with AbbVie and 2023 to see permitted launch dates for those products, according to Biegler and Shmuel.
The biosimilar market could also expand with additional product approvals, said the attorneys. “For example, the FDA recently accepted biosimilar BLAs for Actemra (tocilizumab), a newer reference product first FDA-approved in 2010 for which there are currently no approved biosimilars. Other companies have renewed their commitment to biosimilars.”
Teva and Sandoz are both planning a significant ramp-up in production of biosimilars, with Teva reporting 13 and Sandoz reporting 15 biosimilars in development, they commented.
“This is all in addition to new expected guidance from the courts and regulatory agencies on how to navigate thorny issues related to regulatory approval and patent clearance.”