By Nicholas Mitrokostas and Elaine Blais, Goodwin Procter
The recent settlement of the patent war involving Amgen’s biosimilar to AbbVie’s Humira (adalimumab) has caused rippling in the pharmaceutical industry. The companies had been battling worldwide since at least as early as August 2016, when AbbVie filed a lawsuit against Amgen in the U.S. District Court for the District of Delaware. That lawsuit was triggered by Amgen’s filing of an abbreviated biologics license application (aBLA) to manufacture and sell its own adalimumab biosimilar, Amgevita/Amjevita, in the United States. The settlement resolved the parties’ adalimumab disputes on a global basis. As part of the settlement, Amgen agreed not to launch its product in the United States until January 31, 2023, and in Europe until October 2018. Amgen also agreed to pay an undisclosed amount in royalties for the license to AbbVie’s portfolio of patents, which Amgen conceded were valid. As a result, if it successfully litigates or settles its remaining challenges to the Humira patent portfolio on similar terms, AbbVie could secure another five years of exclusivity over its more than $10 billion U.S. market for Humira. We expect pharmaceutical companies to look to this settlement for lessons learned, including strategies to pursue for successfully resolving patent disputes involving biosimilar products.
By way of brief background, Humira was the first fully human antibody approved by the FDA and was first commercialized in the United States in 2003 for the treatment of rheumatoid arthritis. AbbVie has obtained over 100 U.S. patents concerning Humira. The enactment of the Biologics Price Competition and Innovation Act (BPCIA) as part of the Affordable Care Act paved the way for companies to seek FDA approval of biosimilar products. Humira, with more than $100 billion in total global sales, became a clear target for biosimilar developers. And AbbVie’s efforts to create a patent thicket surrounding the product did nothing to stymie that interest.
Among those interested in the development of a biosimilar to Humira was Amgen. This was a bit of a role-reversal for Amgen, whose own biologics have been the subject of aBLAs. In June 2015, Amgen filed petitions seeking inter partes review (IPR) of two of AbbVie’s patents directed at formulations of Humira. Amgen’s IPR petitions were denied. Separately, in 2016, shortly before Amgen received FDA approval for its product, AbbVie filed a lawsuit for patent infringement against Amgen and for alleged violations of the BPCIA patent dance. AbbVie asserted infringement of 10 patents in this first wave of BPCIA litigation, but claimed an additional 51 patents were infringed by Amgen’s biosimilar.
At the same time, AbbVie has faced other challenges to its HUMIRA patent portfolio, both in the United States and overseas. By way of example, the Patent Trial and Appeal Board (PTAB) instituted review of IPR petitions filed by Coherus BioSciences and Boehringer Ingelheim (BI) involving other AbbVie patents and issued final written decisions invalidating at least three Humira patents. Recently, Coherus and Sandoz filed a number of other IPR petitions challenging AbbVie patents for Humira, all of which remain pending as of publication. In addition, AbbVie is in the early stages of litigation with BI involving its own biosimilar product. And a number of other companies, including Samsung Bioepsis UK and Fujifilm Kyowa Kirin Biologics, have challenged AbbVie patents covering Humira patents overseas. In sum, AbbVie was, and continues to be, facing significant pressure on its exclusivity of Humira in the United States and abroad.
It is not surprising, then, that AbbVie decided to settle its litigation with Amgen, whose Amgevita was FDA-approved in 2016. In doing so, AbbVie bought itself potentially several more years of U.S. exclusivity for Humira. And while still facing challenges from other biosimilar applicants, AbbVie’s settlement indicates to the market the outer end of Humira’s U.S. exclusivity, January 31, 2023. What lessons can pharmaceutical companies developing a biosimilar, or defending another biologic’s exclusivity, take from that settlement?
First, based on the settlement date for the U.S. market, January 2023, AbbVie will have effectively 20 years of exclusivity for Humira unless another challenger is successful in invaliding the patents or settles for an earlier entry date. AbbVie was likely able to negotiate that date, notwithstanding the approval of Amgen’s product over a year ago, because of the tremendous patent portfolio it amassed covering Humira, as well as the product’s large sales. In such a context, a biosimilar applicant might be concerned about launching before final resolution of patent disputes, a scenario that could put the applicant on the hook for enormous lost-profit damages. The fact that AbbVie was able to put off a U.S. biosimilar entry date more than five years through settlement, even while giving up a foreign market (Europe) in 2018, is a reflection of the uncertainty and expense associated with Amgen’s patent challenges in the courts and the U.S. Patent and Trademark Office. Moving forward, one should expect other biologics companies to seek to amass a similarly large portfolio of patents covering their products and to further seek to use that portfolio to maintain additional years of exclusivity through litigation and/or settlement.
Second, other adalimumab biosimilar applicants will likely focus on moving the date of biosimilar competition to a date earlier than January 31, 2023. It is likely Amgen negotiated a “most-favored nation” clause in its settlement agreement, which means another biosimilar applicant that settles for an earlier date or otherwise launches on an earlier date would result in Amgen ability to enter the market prior to January 2023. Nonetheless, other applicants could still benefit from a strategy that increases the pressure on and raises the stakes for AbbVie. Thus, any company that has or is considering filing an aBLA for Humira is likely thinking (or should be thinking) about how to raise the risk for AbbVie and potentially secure a settlement with an earlier entry date.
Third, companies developing adalimumab biosimilars might consider whether an earlier U.S. market entry, even a launch prior to resolution of patent disputes, is a realistic possibility. Should another company launch in that time frame, Amgen (and potentially other companies that may settle in the future) might join the market through accelerating provisions in their agreements. Sharing the risk of a launch for a product the size of Humira shortly before the time when that product was set to lose exclusivity in any event could be lucrative, despite the possibility of damages down the road.
Finally, all companies will be watching for guidance from federal regulatory bodies, such as the Federal Trade Commission (FTC), about how they view settlements for BPCIA patent litigation. Unlike small molecules, biosimilars are not automatically substitutable unless filed and approved as an “interchangeable” product, which means market forces will be more involved in determining their success. This may impact if and how the FTC views settlement agreements to delay entry of a biosimilar after approval but prior to the expiry of patents-in-suit. FTC officials recently indicated biosimilars are on the radar. In a prepared statement before the U.S. House of Representatives Judiciary Committee in July 2017, Acting Director of the FTC’s Bureau of Competition Markus Meier noted that “[i]n particular, the FTC is concerned that branded firms could frustrate the timely entry of biosimilar competitors by restricting access to product samples, erecting roadblocks to the biosimilar firms’ efforts to meet the BPCIA requirements relating to preclinical and clinical testing using reference biologic samples.” Thus, at least for now, one should assume settlements of biosimilar patent disputes may receive some level of scrutiny by antitrust regulators.
In short, the settlement between AbbVie and Amgen provides at least one example of a market pathway for biosimilar applicants and sets some benchmark for what we might expect biologics companies to seek in settling their patent disputes: 20 years of market exclusivity, an earlier entry date in foreign markets, and some sort of licensing royalty. Whether that passes scrutiny with the FTC remains to be seen. In the meantime, we should expect more companies on both sides of the “v.” to follow the model of these two companies.
About The Authors:
Nicholas Mitrokostas and Elaine Blais are partners in Goodwin’s pharmaceutical patent practice and editors of the firm’s award-winning Big Molecule Watch blog.