A few years ago, I wrote about the first emergence of biosimilars on the US market. At the time, everyone was focused on the patent dance – how patent litigation would play out with the new rules. Very little was happening in the product arena. Only one biosimilar had launched as of September 2015 – ZARXIO.
Moving to where we are now, at the end of 2017, the US has 7 biosimilars approved encompassing 5 original biologics (filgrastim/Neupogen; infliximab/Remicade; etanercept/Enbrel; adalimumab/Humira; bevacizumab/Avastin). Europe has approved 25 biosimilars relating to 13 original drugs.
Already the patent litigation has taken off – certainly with starts and stops. The dance appears to be more of a disjointed jig. Quite a bit of controversy over the rules of engagement. The merits of the patents haven’t been on the mainstage much. The first court decision finding patent infringement came out in October, addressing Pfizer’s biosimilar of Amgen’s Epogen, a biosimilar not yet launched in the US, but undergoing manufacturing. Many of the remaining biosimilar litigations are still in early stages of discovery and have been mired in negotiating the dance steps for exchange of information. A few have reached decisions of non-infringement or patent invalidity.
The current group of biosimilars is dominated by some big players – Amgen, Sandoz, Samsung-Bioepis (a JV of Biogen and Samsung). These folks have been in the game with branded and/or generic small molecule drugs. A number of new players made some splash in announcing loaded biosimilar platforms, but as of yet, only one of these, Celltrion, partnered with Pfizer, has a US approval.
So, I got curious – what is happening between biosimilar manufacturers going after the same biosimilar targets? Small molecule drugs that go through the generic drug (Hatch-Waxman) pathway race to be the first generic and can be awarded with 180 days of exclusivity against other generic entrants. That 6 months can be crucial in establishing a good foothold for the first generic in the market. The biologics pathway operates differently. Until a true interchangeable hits the market, there are no exclusivity provisions for the first biosimilar. How will the first biosimilar manufacturers maintain a competitive edge against other biosimilar entrants? Will they develop their own IP and will they use it against other biosimilar entrants?
The answer to the IP development question is yes – at least for some. A number of the biosimilar players have filed patent applications to formulations, as well as methods of making the biologics and purifying them. Some of these patents have issued and others remain pending.
On the biosimilar-to-biosimilar challenge question, perhaps it is too early. The IPR docket shows that players including Sandoz, Celltrion, Coherus, and Samsung-Bioepis have filed challenges to patents protecting the reference biologics. However, as of yet, there doesn’t appear to be any challenges to the second wave of patents coming from the biosimilar manufacturers.
Given that the majority of the US biosimilars only reached FDA approval within the last year or so, and many of these haven’t launched, it may be too early to see IP disputes between competing biosimilar manufacturers. For example, both Amgen and Boehringer are headed towards of biosimilars of AbbVie’s Humira. Boehringer received FDA approval for its biosimilar version CYLTEZO in August, but is not selling it in the US at this time. Amgen recently settled its litigation with AbbVie and agreed to delay the launch of its US biosimilar AMJEVITA until 2023. The 5+ years until launch gives Amgen and Boehringer, as well as other potential biosimilar makers, plenty of time to duke it out.
Another reason for the lack of patent challenges between biosimilar manufacturers may be due to the limited breadth of the patents in their control. These later-filed patents are generally focused on specific methods of producing and purifying proteins and specific formulations. The more tailored claims may not be applicable from one biosimilar manufacturer to another and may have only been filed for defensive purposes.
So, we wait and see – the current litigation and IPR actions are revealing how the reference product and first biosimilar manufacturers are stepping into the patent dance. It will likely take another several years before we see if the second, third and subsequent biosimilar entrants will be tapping each other on the shoulder to cut in on the dance floor.