The first wave of biosimilars began lapping at U.S. shores five years ago when the FDA approved Sandoz Inc.’s Zarxio on March 6, 2015, giving it a label identical to that of its reference biologic, Amgen Inc.’s Neupogen (filgrastim).

Approved two months ahead of schedule as the first test of the 2010 Biologics Price Competition and Innovation Act (BPCIA), Zarxio was greeted as a tide change bringing much needed pricing competition to the U.S. biologics market.

"The approval of Zarxio is quite significant as it paves the way for the future of biosimilar approvals," the FDA's Janet Woodcock said at the time in an email to the staff at the Center for Drug Evaluation and Research. "A successful biosimilars review process will spark the development of a new segment of the biotechnology industry in the United States."

Five years later, Zarxio is the most successful biosimilar to launch in the U.S., having claimed a 50% market share. But the tsunami of biosimilars, and the multibillion dollars of savings they were expected to bring, has yet to wash ashore.

Today, 26 biosimilars referencing nine different biologics have been approved in the U.S.; 15 have launched. Their success varies from product to product. Some biosimilars have struggled to get a foothold, causing lawmakers and policy experts to complain about the sluggishness of the market and to cast blame on the anticompetitive practices of the innovators.

Such complaints ignore that other biosimilars are eroding the innovator’s market. For instance, in one year of being on the U.S. market, biosimilars of Amgen’s Neulasta (pegfilgrastim) had claimed 20% of the market share, Chad Pettit, executive director for global value access and policy for Amgen's biosimilars business unit, told BioWorld. And Pfizer Inc.’s Retacrit, which launched in 2018 as the only FDA-approved biosimilar to Amgen’s Epogen (epoetin alfa), took 22% of the market share within seven months.

In comparison, five epoetin biosimilars were approved in the EU in 2007, offering about a 20% discount from the price of the innovator, Janssen-Cilag Pty Ltd.’s Eprex, which eventually matched the price of the biosimilars. As a result, the five biosimilars together had managed to claim only 12% of Europe’s $1.3 billion epoetin market within five years, according to the EU’s project group on market access and uptake of biosimilars.

2020 a watershed

As more biologics go off patent in the U.S. and more biosimilars flow from the pipeline, 2020 could be a watershed year for the biosimilar market. By the end of the year, $100 billion worth of biologics will be off patent.

That’s a huge opportunity for biosimilars, William Yoon, head of U.S. external engagement and medical advocacy at Sandoz, told BioWorld. As a result, biosimilars could present a savings of $54 billion or more over the next 10 years, he said.

Sheila Frame, vice president of marketing, market access & patient services at Sandoz, echoed his enthusiasm. “We’re very excited about where we think the marketplace is going to go,” she told BioWorld, adding that she’s optimistic about what the future holds for biosimilars.

Along with the patent expirations and the opportunities they provide for the follow-ons, Frame cited a number of factors that should help establish the U.S. biosimilar marketplace. For one, the current focus on prescription drug prices shows biosimilars are a solution, she said. She also noted that various health systems are publishing about their experience with biosimilars. That experience is leading to a change of mindset and more familiarity and confidence in the drugs.

The experience with biosimilars will continue to grow as the number of the follow-ons on the market swells. In the past four months, six new biosimilars have launched, five of which targeted Roche Group drugs:

  • Teva Pharmaceutical Industries Inc.’s Truxima and Pfizer Inc.’s Ruxience, both referencing Roche’s Rituxan (rituximab);
  • Sandoz’ Ziextenzo, referencing Amgen’s Neulasta;
  • Mylan NV’s Ogivri and Pfizer’s Trazimera, both referencing Roche’s Herceptin (trastuzumab);
  • Pfizer’s Zirabev, referencing Roche’s Avastin (bevacizumab);

“Overall, we anticipate that these launches will pave the way to the adoption of additional biosimilars in the United States,” Rick Lozano, vice president of biosimilars & specialty blood products at Amerisourcebergen Corp., told BioWorld.

Not only do the new launches provide competition with the innovator but they also create competition among biosimilars. “The launch of Ziextenzo was a significant milestone for the United States as it was the first time we had three biosimilars competing in one category,” Lozano said, “and now, the United States could see as many as five biosimilars competing with [Roche’s] biologic Herceptin and each other.”

With all six of the new biosimilars treating certain types of cancer, the launches will make the U.S. biosimilar market the most competitive it has been, Lozano said.

Consequently, “2020 will reveal whether this competition of biosimilar products can really increase affordability and access for patients,” he continued. “We hope the increased competition will push larger institutions and payers to make significant formulary decisions, opting to include biosimilars in their plans and ultimately encouraging more manufacturers to invest in these products.”

Lozano and Frame agreed that oncology will be the most competitive space for biosimilars over the next few years. “I think you’ll see some big waves in the next 24 months in the oncology space,” Frame said, adding that immunology will be the next big space after oncology, especially as patents expire on Abbvie Inc.’s Humira (adalimumab) and Amgen’s Enbrel (etanercept).

Those waves will make biosimilars a different market five to seven years from now, Frame said.

Shaping the market

Other events taking place this year will help shape that market. For instance, drugs such as insulin products that were approved as new drug applications will be deemed as biologic license applications March 23. The transition will open those products to biosimilar competition. It also could provide the first testing of the waters for interchangeability, a unique feature Congress included in the BPCIA.

Approval as an interchangeable allows for automatic substitution of a follow-on at the pharmacy, whereas a biosimilar has to be prescribed by name. So far, interchangeability has been a moot point since all the follow-ons approved to date are administered by health care providers – not picked up at the pharmacy.

However, the BPCIA’s differentiation between biosimilars and interchangeability has hindered biosimilars. “The very creation of interchangeability has led to a biosimilar barrier in the U.S.,” Yoon said, as it created a sense that interchangeability is a higher standard. But there is no scientific difference between an interchangeable and a biosimilar, he added.

Meanwhile, ongoing litigation continues to shape the market by further clarifying the BPCIA process. Just this week, the U.S. Court of Appeals for the Federal Circuit heard arguments in Genentech Inc. v. Amgen Inc., in which the Roche unit was seeking a preliminary injunction against Amgen’s at-risk launch of Kanjinti, a Herceptin biosimilar.

Since the launch of the Amgen biosimilar in July 2019, two other Herceptin biosimilars have come to market under licenses from Roche. With those biosimilars on the market, it makes it difficult to show irreparable harm from Amgen’s drug, one of the appellate judges said.

At issue in the appeal was the timing of the request for the injunction. The lower court had denied the request because it was filed 14 months after Roche received Amgen’s BPCIA notice, three months after it received the commercial marketing notice and a month after the FDA approved the biosimilar. “It looks like an ambush on your part,” Judge Evan Wallach told Roche, seeming to agree with the district court.

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