It is widely reported that European biosimilar development is way ahead of that in the US. In a number of ways, this is true. However, when talking about biosimilar development in the EU compared with the US, we really should take a look at the bigger picture.
First of all, let me specify that I’m talking about biosimilar approvals, not launches. In the latter case, the US is way behind, not even viewable in the distance.
Obviously, the US lags because it got a later start, first in promulgating the BPCIA in 2010, and then in developing the biosimilar regulatory pathway. The US system then tried to shoot itself in the foot with the “patent dance,” which also does not exist in the EU. Even America’s inability to master the steps of the patent dance did not deter initial interest in biosimilars, from inside and outside the nation. Overall, the US failed to take great advantage of the pioneering work of European policy makers in divining a regulatory pathway for biosimilars, and has been playing catch up ever since. In a sense, however, the US’s regulatory machinery has caught up, and perhaps exceeded the pace of the European Medicines Agency (EMA) in approving biosimilars.
This is a complicated comparison, outside of numbers alone. The chart below offers a view to the Food and Drug Administration’s (FDA’s) 17 current approvals, all accomplished within seven years of the pathway being available (and the seventh year, 2019, is still young). An analysis of information from the Generics and Biosimilars Initiative demonstrates that only 13 biosimilars were approved in the EU seven years after the pathway was implemented.
A closer look reveals a couple of important points: (1) The EU’s first biosimilar approvals were for growth hormone drugs, which were not considered biosimilar products in the US (until 2020); (2) epoetin biosimilars dominated 2007 approvals with five; and (3) filgrastim biosimilars comprised the main approvals for 2008–2010 in the EU. Between 2009 and 2012, the EMA approved only three biosimilars, two of which were filgrastim molecules. In 2013, an impressive array of biosimilars were approved in the EU, including yet another filgrastim and growth hormone, two infliximabs, and follitropin. The EU has made tremendous progress with new molecules over the past couple of years, including the rush of rituximabs in 2017, and pegfilgrastims and adalimumabs in 2018, all corresponding closely with patent expirations. In fact, of the 54 biosimilars approved in the EU (as of December 2018) in its 13 years of experience with biosimilars, 30 (55%) were approved in 2017 or 2018.
That doesn’t mean the FDA hasn’t made missteps—there have been plenty. Remember, the patent dance was not FDA’s doing, that was statutory not regulatory. They do need to admit their responsibility on the four-digit suffixes and the long delay in finalizing guidances, especially on interchangeability. And there are certainly biosimilar drugs that were approved by the EMA but rejected by the FDA.
Overall though, the FDA has not been the reason only seven biosimilars in four drug classes are now available for prescription. Those are uniquely American problems.
However, the number of patents existing on a specific reference product and the complex nature of the web of exclusivities, has compelled several speakers at a September 4, 2018 public hearing on biosimilars to question the value of the current Purple Book information.
The health care professional community, academia, and patient advocates may take another view: They are complex biochemical medicines and we cannot be sure of their safety and efficacy without carefully controlled studies in large populations. We have been ingrained for 40 years with the need for randomized, phase 3 clinical investigations that it may be very uncomfortable indeed to approve a drug without them.