The U.S. biosimilars market gained momentum over 2018, as more of the agents were submitted for FDA review and more regulatory approvals were granted, including additional immunosuppressive and cancer-treatment biosimilars.
Sandoz’s biosimilar adalimumab, Hyrimoz (adalimumab-adaz) injection was approved in October 2018, and Celltrion’s Truxima (rituximab-abbs), the first biosimilar to be approved in the U.S. for non-Hodgkin lymphoma and the first approved biosimilar to Rituxan, was approved in November 2018.
“We’re just seeing the cusp or initial wave of these cancer-treating biosimilars,” says Gary H. Lyman, MD, MPH, FASCO, FRCP, professor of medical oncology at the University of Washington School of Medicine, in Seattle. Lyman also serves as chair of the American Society of Clinical Oncology (ASCO) Biosimilars Work Group.
In May 2018, the FDA approved a biosimilar version of epoetin alfa (Epogen/Procrit), called Retacrit (epoetin alfa-epbx), for treatment of chemotherapy- and kidney disease-associated anemia, as well as for anemia resulting from zidovudine among HIV-positive patients. In June, the FDA approved Mylan and Biocon’s application for Fulfila (pegfilgrastim-jmdb), the first biosimilar to Neulasta (pegfilgrastim) for reducing infection risk in some patients with non-myeloid cancers who are administered myelosuppressive chemotherapy.
There are now 15 FDA-approved biosimilar products, up from nine in 2017. Of the four oncology biosimilars approved in 2018, three have already gone to market, says Rick Lozano, vice president of biosimilars and integrated business development, AmerisourceBergen.
Additional biosimilars approvals are coming in 2019 and more applications will be submitted, as more brand-name biologics’ patent protection periods expire.
“The regulatory framework is pretty well settled now,” Lyman says. “We’re still waiting for the final rules for some of the other aspects of biosimilar approval, such as substitution and interchangeability.”
Biosimilars do not have to be declared interchangeable with their reference brand-name biologics to be prescribed, but an interchangeability determination would allow substitution by pharmacists.
“While it will take time for us to fully benefit from recent regulatory updates, the changes and communications we saw coming from policy makers in 2018 were incredibly promising and present great opportunities for 2019,” Lozano says. “Looking ahead, policy makers are seriously exploring the interchangeability between biosimilars and their reference products as part of the blueprint for lowering drug prices.”
Congress and the FDA made it clear in 2018 that biosimilars “will be part of the solution” for controlling healthcare costs, Lozano says. “That alignment is starting to better pave the way for more products to come to market, as evidenced by this year’s uptick in approvals.”
The FDA is also preparing new guidelines on biosimilar product labels, which Lozano hopes will create a “more level playing field” between biosimilars and biologics by helping to reassure healthcare providers that biosimilars are safe and effective.
Lozano expects to see continued momentum in 2019, with more approvals and increasing acceptance of biosimilars as a viable treatment option.
“We are confident that the U.S. market will continue to evolve in the direction of the European biosimilar market, as more and more obstacles, such as patent challenges and litigation, are reduced,” he says
Will the U.S. catch up to Europe?
The U.S. has lagged behind Europe on biosimilars approvals and uptake, and some analysts have pointed to uncertainty about anticipated cost savings, regulatory and legal issues, contracting mechanisms, and physician unfamiliarity with biosimilars as potential barriers to uptake.
Because biosimilars are “highly similar” but not identical, on a molecular level, to originator biosimilars, some clinicians have had concerns about the idea of switching patients from well-known biologics to less familiar biosimilars. Patients have been switched to biosimilars in most cases only after brand-name biologics lost efficacy or brought intolerable toxicities.
“Europe has been ahead of the United States on biosimilar approvals for years but the good news is this: none of them have been withdrawn from the [European] market or seen red flags with major safety or efficacy issues,” Lyman says. “Nevertheless, recently, a submission for a biosimilar for rituximab for lymphoma was turned down by the FDA, for reasons they know and I don’t, and the company has decided not to challenge or resubmit.”
Cancer biosimilars take center stage
“Over the past year, for the first time, we have had a number of oncology biosimilars FDA-approved for cancer treatments as opposed to supportive care agents like growth factors,” Lyman says, citing approvals since September 2017 for the biosimilars Mvasi (bevacizumab-awwb), Ogivri (trastuzumab-dkst), Ixifi (infliximab-qbtx), Hyrimoz, and Truxima.
The first biosimilar approval was for Zarxio (filgrastim-sndz), a biosimilar G-CSF myeloid growth factor used in supportive cancer care, which was approved back in March 2015. In 2018, three more filgrastim and pegfilgrastim biosimilar products were approved.
But Lyman cautions that biosimilars are still in their early days.
“Biosimilar trastuzumab and bevacizumab were approved in December 2017, but both of these met with delays and even now they are just beginning to enter the marketplace, so we really don’t yet have data on their uptake,” he says.
Oncology biosimilars have been “mainly a good-news story,” Lyman says.
“We have multiple new approvals and the approval process seems to be going smoothly—with perhaps one glitch that was part of the growing pains of a new process,” he says.