In 2004, the European Commission (EC) passed legislation creating the world’s first biosimilars approval pathway, and in 2005 and 2006 the European Medicines Agency (EMA) released its first set of biosimilar guidelines.  Since then 23 biosimilars have received marketing authorization in Europe. Over that time, researchers have accumulated substantial, real world evidence (RWE) confirming their clinical comparability with originators and there have been no reported safety issues when compared with the originators.

The US has been slower to embrace biosimilars, though regulators are beginning to catch up. In 2010, the US created a dedicated regulatory pathway for the approval of biosimilars as part of the Patient Protection and Affordable Care Act (PPAC Act). And in 2012, the US Food and Drug Administration (FDA) released draft guidance providing step-wise considerations for nonclinical and clinical biosimilar development, which was finalized in 2015. By November of 2016, FDA had approved four biosimilars, however all five faced patent challenges and their launches were delayed due to issues related to patents.

This is promising for developers interested in producing biosimilars for the US market, particularly as this field is one of the fastest growing pharmaceutical sectors globally, with many biologics reaching patent expiration in the next few years. It has been projected that more than 30 innovator biologics -- with global sales of more than US $79 billion—will have lost patent protection by the end of 2018. Increasing numbers of biopharmaceutical companies—including those originally committed to developing innovative drugs only—are eager to take advantage of the opportunity presented by biosimilars in the US. However, they still face many challenges. Their success will be related not only to the timing of expiration of the originator’s patents, but also to the companies’ technical and financial ability to manufacture sufficiently comparable products. Considerable resources are required to finance the necessary studies and to protect the biosimilar sponsor during patent litigation.

Patents and IP

Because this is a nascent industry in the US, regulations and policies are still evolving, and pharma companies need to stay abreast of changes if they want to successfully navigate the market.

For example, through the Biologics Price Competition and Innovation Act (BPCI Act)—part of the Patient Protection and Affordable Care Act (PPAC Act) of 2010—the biotechnology industry won its long fight to preserve a lengthy period of exclusivity for innovator products. New innovator biologics are currently granted 12 years of market exclusivity, compared to the average three-to-five years of exclusivity for small-molecule drugs—but this decision may now be in question. In an effort to drive prices down, debate continues around reducing the biologic exclusivity period from 12 years to seven, which is more in line with other countries.

Developers should also pay attention to ongoing patient litigation. Under the PPAC Act, there was a complex scheme for resolving patent disputes, often referred to as the patent dance. The biosimilar applicant and the originator company were intended to engage in an elaborate negotiation to determine which patents will be addressed in litigation. However, the detailed disclosure of manufacturing information prompted several biosimilar applicants to sidestep the patent dance to protect confidential trade secret information.

In January 2017, the US Supreme Court said it would review whether biosimilar companies should have to wait six months after FDA approval before launching their follow-on products. The decision involved Sandoz’s Zarxio (filgrastim-sndz), which came to market as a biosimilar version of Amgen’s Neupogen (filgrastim). The Supreme Court’s decision to hear the case was unexpected as so few biosimilars have come to market in the US, and in December 2016, the Supreme Court declined to hear a similar dispute between Amgen and Apotex.

In June 2017, the Supreme Court, by a 9-0 ruling, overturned the lower court decision that had prevented Novartis from selling its biosimilar version of Amgen's Neupogen (filgrastim) until 180 days after gaining FDA approval. The court also determined that patent holders cannot compel companies developing biosimilars to provide information about their products.

This could lead to more rulings in the coming years, but, for now, it means that biosimilars will now be able to reach the market sooner.

Biosimilar litigation has already been directed at some of the most successful biologic products, including Enbrel, Humira, Neulasta, Neupogen and Remicade. Future years promise more challenges and further court interpretation of the patent aspects of the PPAC Act.

How to respond

To succeed in the marketplace, companies need to stay up-to-date of the complex and evolving IP and patent landscape. Originator biologic manufacturers are implementing sophisticated lifecycle plans, including filing for new patents and developing improved formulations to protect their branded products from biosimilar competition. To manage these issues, biosimilar sponsors will need to budget for defense against legal actions by originator companies as their patent protection comes to an end.

Because regulatory professionals are increasingly being asked to weigh-in on biosimilar programs and participate in due diligence teams, they need to be familiar with the IP investigations and assessments for biosimilar programs. This knowledge will enable their employers to better understand the risks associated with the inevitable patent challenges rising with financially successful branded products and potential threats from third-party patent owners. Knowledge of the patent landscape and regulatory exclusivity surrounding biosimilar patent life is also required to better understand risk, forecast revenue, seek price concessions or obtain valuable contract language to mitigate risk. 



About The Authors

Vice President, Global Strategic Drug Development and Head of Global Biosimilars Strategic Planning

Recent thinking: Biosimilars or biobetters?

Vice President Strategic Drug Development, Head, Biosimilar Center of Excellence

Recent thinking: Biosimilars or biobetters?