Correction: An earlier version of this article incorrectly identified Amgen as producer of the drug Humira. AbbVie has the rights to and markets Humira.
Compared to Europe, the U.S. biosimilars market remains in its infant stages. However, the pace of growth could be shifting into higher gear with the U.S. approval of Novartis’ Zarxio and Pfizer/Celltrion’s Inflectra. However, the two drugs could have very different trajectories post-launch.
Zarxio, a copy of Amgen’s cancer drug Neupogen, cleared regulatory review by the Food and Drug Administration in March 2015 while Inflectra, a biosimilar of Janssen’s blockbuster inflammatory drug Remicade, won approval earlier this month.
The two biosimilars received similar treatment from the FDA. Both Zarxio and Inflectra are approved for the full range of indications held by their reference biologic. And like Zarxio, Inflectra was also approved as a biosimilar, rather than as an interchangeable drug. This means both cannot be substituted for the branded biologic at the discretion of a pharmacist.
It would appear the Pfizer/Celltrion team could follow Zarxio’s lead in navigating the U.S. biosimilars market. But Kate Keeping, senior director of biosimilars research at Decision Resources Group, says that may not be the case.
Different drugs, different challenges
Although two approved biosimilars do not represent a robust biosimilars market by any stretch of the imagination—especially considering the fact that there are 20 approved biosimilars in Europe—the US market is growing, diversifying, and becoming more complex.
With two approvals under its belt, the FDA is gaining experience and comfort with processing biosimilar applications, which should in turn help manufacturers. But consistency on the regulatory end may not translate to similar launch experiences.
“While it’s true that the progress that Sandoz has made with Zarxio may have helped in terms of the Biologics Price Competition and Innovation Act (BPCIA) regulatory process, the launch of Inflectra will be completely different than the launch of Zarxio,” Keeping said.
“Gastroenterologists and rheumatologists are likely to be a lot more conservative about uptake than oncologists for several reasons. Oncologists can look to Europe, where biosimilar Neupogen has been used for almost a decade, compared with just a couple of years for biosimilar Remicade,” she explained further.
There is also the challenge of addressing the concerns that physicians have about indication extrapolation—a process where the FDA can approve a biosimilar for indications held by the reference drug but weren’t directly studied. “Gastros have more concerns about indication extrapolation than rheumatologists, because Inflectra was not tested in gastro patients,” Keeping said.
In contrast, rheumatologists have a lot of clinical data to draw on, including independent study data from Europe. One study presented at the European League Against Rheumatism meeting in Dublin last summer highlighted a meta-analysis of 14 randomized, controlled trials assessing the safety of Inflectra in 1,454 patients with rheumatoid arthritis (RA) or ankylosing spondylitis. The data demonstrated Inflectra was both safe and effective among these populations.
But this data may not be enough to guarantee aggressive uptake among rheumatologists in the U.S., where the preferred first-line treatment options for RA remain Enbrel and Humira.
Additionally, some physicians may opt to use Inflectra only for treatment of new patients over concerns about immunogenicity.
Furthermore, Keeping noted that anti-TNG drugs like Remicade are generally used to treat chronic diseases over the course of a lifetime. Neupogen, and by extension Zarxio, is used only for a limited period of time.
The payer perspective
Payers are more likely to be open to Inflectra given their concern about the financial burden of using biologics to treat chronic immune-related conditions, according to Keeping. These conditions are associated with a significant financial burden—Remicade generated $4.5 billion in sales in the US last year. Of course, payer interest will also be affected by how much Inflectra is discounted versus Remicade.
Sandoz initially discounted Zarxio by 15% compared to the price of Neupogen – a significant price gap but less that what is sometimes seen in generic pricing. It is unclear yet what price Inflectra will carry in the U.S.
A shifting market
Inflectra may also face patent infringement litigation from Johnson & Johnson (the parent company of Janssen). J&J has said it would view any market launch of Inflectra in 2016 as patent infringement. Some of the U.S. patents on the drug don’t run out until 2018.
In a recent report on the outlook for the global pharmaceutical industry, the ratings agency Moody’s indicated biosimilar growth in the U.S. will speed up due, in part, to a number of blockbuster drugs hitting the end of their patent lives.
The FDA has already accepted six other biosimilar applications, including one for a copy of AbbVie’s bestseller Humira. Approvals for biosimilars for Amgen’s Neulast and Epogen are likely and the FDA could act on Humira by September 2016, according to Moody’s.
Respondents to BioPharma Dive’s first State of Drug Development survey picked up on this hastening pace of U.S. growth, selecting biosimilars as the most promising drug class.
While the trajectory for Zarxio and Inflectra remains somewhat unclear, it is apparent biosimilars will begin to exert a greater deal of competitive pressure on biologics over the next one to two years.