Year in Review: Top Legal Developments of 2023

As we settle into 2024, we reflect on the significant legal developments of 2023 that hold potential impact on the biologics and biosimilars market.  The following is a recap of some of the top five legal decisions and developments in the biosimilars and biologics space in 2023 that we covered on the Big Molecule Watch.

  1. Regeneron’s Suits Against Proposed Biosimilars of EYLEA

The year 2023 saw significant developments in litigation related to biosimilars referencing Regeneron’s EYLEA (aflibercept) product.  In June 2023, an expedited trial was held in the Northern District of West Virginia on Regeneron’s BPCIA suit against Biocon, successor in interest to Mylan.  As we have reported, Regeneron sought, and was granted, an expedited trial—just 10 months after filing its complaint—in order to get an opportunity to gain the benefit of a statutory permanent injunction available under 35 U.S.C. 271(e)(4)(D).  The Court entered a mixed judgment on December 27, 2023, holding that the asserted claims of a Regeneron formulation patent were valid and infringed and that asserted claims of two of Regeneron’s dosing patents were invalid.  No appeal has been filed to date

Shortly before judgment in the trial against Biocon, Regeneron filed BPCIA complaints in the Northern District of West Virginia against Celltrion (on November 8), Formycon (on November 29), and Samsung Bioepis (on both November 22 and December 27, 2023).  Shortly after filing these suits and the day after the Biocon trial judgment, Regeneron filed emergency motions on December 28 for entry of a preliminary injunction (PI) schedule in these second-wave aflibercept BPCIA cases, citing Celltrion’s provision of Notice of Commercial Marketing (NCM) and generally referencing the 180-day clock provided for PI proceedings after receipt of NCM.  In parallel with seeking a PI schedule, Regeneron also moved on December 22, 2023 for authorization of alternative service via e-mail.

Stay tuned to Big Molecule watch for further developments on these litigations in 2024, including developments on the IPRs related to Regeneron’s patents directed to dosing of aflibercept .

  1. Passage of and Challenges to the Inflation Reduction Act

In August 2023, HHS announced the ten drugs that will be included in the first year of the Inflation Reduction Act’s new Drug Price Negotiation Program. They are:

  1. Eliquis (apixaban, Bristol Myers Squibb)
  2. Jardiance (empagliflozin, Boehringer Ingelheim)
  3. Xarelto (rivaroxaban, Janssen Pharms)
  4. Januvia (sitagliptin phosphate, Merck Sharp Dohme)
  5. Farxiga (dapagliflozin, AstraZeneca AB)
  6. Entresto (sacubitril; valsartan, Novartis Pharms Corp)
  7. Enbrel (etanercept, Immunex)
  8. Imbruvica (ibrutinib, Pharmacyclics LLC)
  9. Stelara (ustekinumab, Centocor Ortho Biotech Inc., Janssen Biotech)
  10. Fiasp; Fiasp FlexTouch; Fiasp PenFill (insulin aspart, Novo); NovoLog; NovoLog FlexPen; NovoLog PenFill (insulin aspart recombinant, Novo Nordisk Inc.)

Since its passage and the announcement of the drugs that would be part of the program, six of the manufacturers whose drugs are on the list and several other interested groups have filed lawsuits challenging the Program. Legal challenges to the IRA are ongoing, including a denial of a preliminary injunction motion and motion to dismiss, and new complaints filed by challengers of the statute.

  1. PTAB Challenges Relating to SOLIRIS (eculizumab) and  STELARA® (ustekinumab)

There was also a lot of action at the PTAB this year related to biologic drugs.  In May and June, Samsung filed five IPR petitions challenging all claims of four patents assigned to Alexion relating to SOLIRIS (eculizumab) in IPR2023-00933, IPR2023-00998, IPR2023-00999IPR2023-01069, and IPR2023-01070.  The challenged claims related to various aspects of  SOLIRIS (eculizumab) including pharmaceutical dosages and methods for treating paroxysmal nocturnal hemoglobinuria with eculizumab.  In December 2023, the PTAB instituted all of these IPR petitions.

Samsung also filed IPR2023-01103 in June, challenging all claims of a patent assigned to Janssen that related to methods for treating ulcerative colitis with ustekinumab, the active ingredient in Janssen’s STELARA product.  That IPR was terminated in August in view of a settlement agreement and before there was any decision on institution.  Biocon Biologics then filed its own IPR on the same patent in IPR2023-01444.  That petition is pending.

  1. REGENXBIO Sues Sarepta Therapeutics for Patent Infringement on Gene Therapy Product

In June, REGENXBIO and the Trustees of the University of Pennsylvania filed suit in Delaware against Sarepta Therapeutics, claiming that Sarepta’s adeno-associated virus (AAV) technology gene therapy product infringes U.S. Patent No. 11,680,274.  The patent covers an AAV capsid and a minigene used in delivering a transgene into cells for gene therapy.  REGENXBIO alleges that Sarepta is making, using, and building a commercial stock of the product in the U.S., with plans to commercialize it upon FDA approval.  Two days after the lawsuit, Sarepta announced FDA approval for its product, SRP-9001, intended for treating Duchenne muscular dystrophy in pediatric patients aged 4 through 5 years, with a confirmed mutation in the DMD gene.  The FDA had accepted the Biologics License Application for priority review in November 2022.

Before the most recent suit was filed, in September 2020, REGENXBIO had previously sued Sarepta on a different patent,  U.S. Patent No. 10,526,617 (the ’617 Patent), which is generally directed to host cells comprising adeno-associated virus (“AAV”) sequences encompassing AAV-rh10 and AAV-rh74.  That case was set to go to trial in January 2024, but on January 5, 2024, Judge Richard Andrews of the U.S. District Court for the District of Delaware District Court granted summary judgment for Sarepta and ruled that the ’617 Patent was invalid as being directed to ineligible subject matter.  The Court held the claims of the ’617 Patent are invalid under § 101 because the isolated AAVrh.10 sequences are not different from those found in nature and isolation alone is not sufficient to create patentable subject matter.  Stay tuned for more coverage on the anticipated appeal of this case, as well as the case filed in 2023.

  1. Antitrust Litigation Updates

The year 2023 also saw a lot of activity in antitrust litigation related to biologic drugs.

For example, Amgen failed to throw out Regeneron’s antitrust lawsuit in the U.S. District Court for the District of Delaware involving allegations that Amgen violated antitrust laws by engaging in an exclusionary campaign against Regeneron’s cholesterol-reducing medication, PRALUENT.  Regeneron claims Amgen seeks to avoid competing on the merits, as PRALUENT is a direct competitor to Amgen’s REPATHA.  Both drugs are PCSK9 inhibitors designed to lower low-density lipoprotein cholesterol.  On August 8, 2022,  Amgen filed a motion to dismiss and to stay the antitrust complaint, arguing that Regeneron’s allegations fall short of stating an antitrust violation and requesting a stay pending the resolution of related patent litigation before the Supreme Court.  On Feb 10, 2023, Magistrate Judge Hall recommended denying Amgen’s motion to dismiss, noting that Regeneron adequately pled antitrust violations, though expressing reservations about a specific claim.  The motion to stay was denied without prejudice, with Judge Hall citing the potential complication of the case and significant prejudice to Regeneron if delayed.

In a March 21, 2023 opinion, Judge Andrews adopted the magistrate judge’s recommendation and denied Amgen’s motion to dismiss.  That case is ongoing with a jury trial set for November 2024.

An antitrust litigation filed against Johnson & Johnson and Janssen Biotech, Inc. related to J&J’s REMICADE (infliximab) product came to a conclusion in 2023.  In that case, the class actions were brought by employee welfare benefit plans, specifically the National Employees Health Plan, the Welfare Fund of Plumbers Local Union No. 200, and the Local 295 IBT Employer Group Welfare Fund.  The class action cases brought by the welfare benefit plans followed an earlier antitrust complaint filed by Pfizer against J&J and Janssen.  The class action plaintiffs alleged that J&J “worked to suppress competition and raise prices to purchases of [REMICADE] by imposing a web of exclusionary contracts on both health insurers and healthcare providers.”  Further, the complaints alleged that, when Pfizer launched its competing INFLECTRA (infliximab-dyyb) product in 2016, J&J “deployed improper exclusionary tactics to maintain the dominance of its flagship product.”

Discovery in the indirect-purchaser antitrust actions were consolidated with discovery in the antitrust action brought by Pfizer.  As we previously reported, the Pfizer antitrust action settled in 2021.

In April 2022, the parties in the indirect-purchaser antitrust class action stipulated to a $25 million settlement and the court preliminarily approved the settlement in August 2022.  In March 2023, the court granted Plaintiffs’ Motion for Final Approval of Settlement, Plan of Allocation and Distribution, Award of Attorneys’ Fees and Expenses, and Service Awards, which among other things, awarded class counsel $7 million in attorneys’ fees and $2.3 million in expenses.