• FDA approves the second Enbrel® (etanercept) biosimilar—no etanercept biosimilar has launched in the United States to date.
  • FDA approves the fourth Herceptin® (trastuzumab) biosimilar—no trastuzumab biosimilar has launched in the United States to date.
  • European Medicines Agency approves ninth and tenth adalimumab biosimilars and second bevacizumab biosimilar.

As pharmaceutical drug costs attract increasing media attention and political scrutiny, a growing number of biosimilar drugs are set to enter the U.S. and European markets in the coming years.  Global sales for the top ten branded biologic drugs totaled approximately $71 billion in 2017[1].  In July 2018, Health and Human Services Secretary Alex Azar announced a Biosimilars Action Plan to aid the development of a market for biosimilars in order to increase competition for biologic drugs, which make up 40% of U.S. pharmaceutical spending.  Competition in the heavily regulated marketplace for these blockbuster therapeutics is expected to substantially impact the pharmaceutical industry and national health systems.  To date, the U.S. has considerably lagged behind Europe’s expansion of biosimilar drug options.  The RAND Corporation estimates that biosimilar products can save the U.S. health system approximately $54 billion over the next decade, as discussed here.

Since 2005, the biosimilar regulatory framework in Europe has been implemented through the Committee for Medicinal Products for Human Use (CHMP) under the European Medicines Agency (EMA).  The CHMP provides initial assessments for marketing authorization of new medicines that are ultimately approved centrally by the EMA.  Since Sandoz’s somatotropin biosimilar Omnitrope® was first authorized on April 12, 2006, an additional 59 applications have been approved in Europe.  Six of the authorizations have been withdrawn post-approval (Table 1).

The U.S. did not implement a regulatory framework for biosimilar evaluation until after enactment of the Biologics Price Competition and Innovation Act (BPCIA) of 2009.  Given that the first U.S. biosimilar drug was approved almost a decade after the first in Europe, the number of authorized biosimilar drugs in Europe far exceeds the number of biosimilars approved in the United States.  Sandoz’s filgrastim biosimilar, Zarxio®, received the first U.S. approval in 2015, whereas nine filgrastim biosimilars have been approved in Europe dating back to multiple authorizations in 2008.  Zarxio® (in the U.S.) and Zarzio® (in Europe) are biosimilar to the reference product Neupogen® marketed by Amgen and originally licensed in 1991.  Subsequent to Zarxio®’s approval, 18 other biosimilar drugs have gained U.S. approval to date (Table 2).

As illustrated in the following graph, while the EU’s significant head start led to an imbalance in the number of biosimilar drugs available in the respective markets, the EU’s relatively higher rate of approvals in recent years has widened its lead over the United States.

Currently, six biosimilar applications are under review by the EMA for marketing authorization (Table 3).  As an increasing number of patents expire on blockbuster biologic drugs, the number of abbreviated biologics license applications is also increasing.  Biosimilars for at least 23 different original biologics are currently navigating biosimilar pathways or are in late stage development in the U.S. (Table 4).

On April 29, 2019, Samsung Bioepis announced the approval of its etanercept biosimilar EticovoTM.  “The approval of ETICOVO adds to our growing portfolio of anti-TNF medicines in the US, where we believe biosimilars can bring meaningful value to the country’s healthcare system,” said Christopher Hansung Ko, President & CEO of Samsung Bioepis. “Through relentless process innovation and an uncompromising commitment to quality, we remain dedicated to advancing one of the industry’s strongest biosimilar pipelines.”  In addition to the United States, Samsung Bioepis’ etanercept biosimilar has been approved for marketing in 38 countries, namely 28 European Union (EU) member states, the European Economic Area (EEA) member states of Norway, Iceland and Liechtenstein, as well as Switzerland, Canada, Brazil, Australia, New Zealand, Israel, and Korea.

In April 2019, the EMA approved two more adalimumab biosimilars to Abbvie’s Humira® in Europe, bringing the total number of approved adalimumab biosimilars to ten.  In February 2019, the EMA approved Pfizer’s Zirabev, which is the second bevacizumab biosimilar to Genentech and Roche’s Avastin® approved in Europe.

The FDA has recently provided useful guidance as reported here.  Under the leadership of Dr. Scott Gottlieb, the FDA advanced new policies aimed at promoting more competition when it comes to biosimilar products as outlined in Dr. Gottlieb’s December 11, 2018 statement on new actions advancing the agency’s biosimilars policy framework.  However, with Dr. Gottlieb’s unexpected resignation on March 5, 2019, it will be up to the next permanent successor to guide stakeholders in navigating the FDA approval process.

Table 1. European Medicines Agency List of Approved Biosimilar Drugs (updated May 6, 2019).

Table 2
. U.S. Food and Drug Administration List of Approved Biosimilar Drugs.

Table 3. European Medicines Agency List of Biosimilars Under Evaluation for Marketing Approval (Source: EMA list of applications for new human medicines compiled on April 8, 2019 and published on April 15, 2019).

Table 4. Biologics having already expired or nearing primary patent expiry in the U.S. and biologics that have biosimilars in the regulatory pipeline.

[1] Based on sales reported by respective manufacturers (1. Humira—Abbvie, 2. Rituxan—Roche, 3. Enbrel—Pfizer/Amgen, 4. Herceptin—Roche, 5. Avastin—Roche, 6. Remicade—Johnson & Johnson/Merck, 7. Lantus—Sanofi, 8. Neulasta—Amgen, 9. Avonex—Biogen, 10. Lucentis—Roche/Novartis).