Legislative riddles hand courts vital role in shaping biosimilar path

The FDA's slow pace of developing a U.S. biosimilar path that already trails that of other markets has drawn sharp rebukes from Congress and critics, but the regulator isn't the only force shaping the path.

Even as the agency ponders the science and consequences of potential guidance while mulling its way through biosimilar reviews, the courts are deciding the parameters of the ambiguities of the Biologics Price Competition and Innovation Act (BPCIA), as well as the workings of the America Invents Act (AIA), which created a new junction for clearing patents ahead of the launch of biosimilars.

"We have a long and very interesting road ahead," Scott Cunning, a partner at Haynes and Boone LLP, toldBioWorld Today, noting that every aspect of the BPCIA and its intersection with the AIA will undoubtedly be teased out in the courts.

He pointed out that in the 30-plus years since Hatch-Waxman created a generics path, there's been no end to the level of creativity from both brand and generic drug companies in questioning every part of that legislation. "We're just at the very beginning of BPCIA," he said.

Given the reaction of the courts to the BPCIA, there's a lot to tease out. When the U.S. Court of Appeals for the Federal Circuit handed down its split decision last year in Amgen Inc. v. Sandoz Inc. – its first involving the BPCIA – Judge Raymond Chen wrote in his partial dissent, "As the majority opinion recognizes, this case requires us to 'unravel the riddle, solve the mystery and comprehend the enigma' that is the BPCIA. . . . To fulfill our judicial obligation 'to say what the law is,' we must choose from a series of imperfect choices." (SeeBioWorld Today, July 22, 2015.)

The challenges, however, won't stop with the BPCIA and AIA. Courtenay Brinckerhoff, a partner with Foley & Lardner LLP, expects some of the FDA's biosimilar guidances, once they're finalized, to be tested in court.

Then there will be the patent challenges – lots of them. Stacie Ropka, of Axinn, Veltrop & Harkrider LLP, said sponsors of biologics that may someday be targeted by biosimilars are already building thicker patent fences to protect their products from competition as long as possible. In addition to claiming the molecule itself, they are filing patent claims on everything imaginable – new indications, the methods to grow and harvest cells, manufacturing processes and the devices used to administer the drug, Ropka told BioWorld Today.

Elaine Blais and Robert Cerwinski, partners at Goodwin Procter LLP, agreed. Innovators have been thinking about biosimilars for a long time, Blais told BioWorld Today, so they've been protecting every aspect of their product and are aggressively defending their intellectual property (IP).

That includes trademarks, which can be used, in addition to patents, to protect device technology, Cerwinski said. Under the BPCIA, a biosimilar has to follow the same dosage and route of administration as the innovator, which could lead to infringement claims.

The IP protecting Humira (adalimumab), the nation's top-selling drug, is a harbinger of the future, Cerwinski told BioWorld Today. Abbvie Inc. has protected its investment in the drug by creatively layering its patents while making improvements and following a life cycle approach. So far, its patents have withstood an inter partes review (IPR) challenge by Amgen, which has a biosimilar application referencing the biologic under review at the FDA. (See BioWorld Today, April 26, 2016.)

Innovators aren't the only ones filing patents, though. Citing the complexities of biologics, Cunning said there's room for biosimilar sponsors to patent processes and devices to administer their follow-ons. As a result, he expects to see future patent litigation between competing biosimilars. But there's nothing in the BPCIA to address those challenges or even suggest patent exchanges with the sponsor of a marketed biosimilar.

WAITING FOR DIRECTION

While biologics companies continue to innovate, copy and patent, they're still waiting for the Supreme Court to give its first direction on the BPCIA. Sandoz has asked the court to overturn last year's fractured Federal Circuit decision that said a biosimilar maker cannot send the required 180-day notice of commercial marketing until after the FDA has approved the follow-on. That decision forced Sandoz to delay its launch of Zarxio, the nation's first biosimilar and a follow-on to Amgen's Neupogen (filgrastim), for a few months.

In response, Amgen asked the court, if it decides to take up the case, to also rule on the Federal Circuit's decision that the patent exchange laid out in the BPCIA is optional.

The Supreme Court will likely decide in June whether it will hear the case, Brinckerhoff told BioWorld Today. If the court grants cert, it wouldn't hear arguments until late this year or early next, which means a final answer on the two basic questions could be a year away. But Brinckerhoff and others aren't convinced the high court will wade in on this one. (See BioWorld Today, Oct. 20, 2015.)

In the meantime, the Federal Circuit's decision on the 180-day notice is the law of the land. When Celltrion Inc.'s biosimilar to Remicade (infliximab, Janssen Biotech Inc.) was approved earlier this month, the expectation was that Pfizer Inc., which will market the drug in the U.S. as Inflectra, wouldn't launch it until at least October because of that ruling.

While Pfizer, of New York, said it was continuing with the preparation of launch plans for 2016, it declined to comment on whether it had submitted a notice of commercial marketing to Janssen following the FDA's approval. (See BioWorld Today, April 6, 2015.)

The breadth of the Federal Circuit's decision is being tested in other biosimilar cases. For instance, the timing of the marketing notice is at the heart of a case being pursued by Amgen against Apotex Inc.'s biosimilar to Neulasta (pegfilgrastim) in the U.S. District Court for the Southern District of Florida. (See BioWorld Today, Aug. 12, 2015.)

Unlike Sandoz, Apotex followed the BPCIA's patent exchange, so the six-month waiting period after licensure serves little purpose under the Federal Circuit's explanation that the wait gives the innovator time to pursue infringement action.

BIOSIMILARS AND IPRs

As industry waits for the Supreme Court to weigh in on the first BPCIA issues, the justices are looking at other questions that could shape the biosimilar path. Just this week, they considered arguments on the standard the Patent Trial and Appeal Board (PTAB), set up under the AIA, should use in hearing patent challenges in an IPR.

Although Congress conceived the IPR as a less costly, faster alternative to challenging patents on the basis of obviousness, it is becoming an add-on to what is already a long litigation process for drug companies. Since PTAB uses a different review standard than the courts, conflicts are bound to occur – a point that seemed to trouble Chief Justice John Roberts during Monday's argument.

Regardless of how the Supreme Court rules in Cuozzo Speed Technologies LLC v. Lee, "IPR is going to be a valuable tool for biosimilar applicants," Cunning said. With an IPR, there is no presumption of patent validity as there is in court. That may make it easier, and cheaper, for a biosimilar sponsor to knock down some of the innovator's patents, especially since the courts so far have decided a biosimilar sponsor can't file for a declaratory judgment to invalidate a patent.

However, the IPR, especially where it intersects with the BPCIA path, opens up even more avenues for legal challenges that might need to be smoothed out in the courts.

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