• U.S. Food & Drug Administration and European Medicines Agency approve first trastuzumab biosimilars
  • U.S. Food & Drug Administration approves a second infliximab 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 nine branded biologic drugs were estimated to total $63 billion in 2016[1].  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 37 out of 42 applications have been approved in Europe.  Three of the authorizations have been withdrawn post-approval by the marketing authorization holders (Table 1).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, only eight other biosimilar drugs have gained U.S. approval to date (Table 2).  As illustrated in the following graph, the EU’s significant head start led to the existent imbalance in the number of biosimilar drugs available in the respective markets.

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

On December 1, 2017, Mylan and Biocon announced that the FDA approved OgivriTM, a trastuzumab biosimilar to Roche’s Herceptin®.  This is the first Herceptin® biosimilar approved by the FDA, and it follows the EMA’s approval of the first Herceptin® biosimilar (Ontruzant®) in November 2017.  No launch date has been set for OgivriTM in the United States.

On December 13, 2017, Pfizer announced that the FDA approved IxifiTM, a infliximab biosimilar to Pfizer’s Remicade®.  This is the second infliximab biosimilar approved by the FDA after Inflectra®’s approval in 2016.  Pfizer currently has no plans to launch IfixiTMin the United States, according to Pfizer spokesperson Thomas Biegi, because Pfizer already markets Inflectra® in the U.S.

On January 15, 2018, the EMA approved MvasiTM, the first bevacizumab biosimilar to Roche’s Avastin in Europe.  The FDA previously approved MvasiTM in September 2017.  MvasiTM is the first product from Allergan’s collaboration with Amgen to receive authorization from the European Commission according to David Nicholson, chief research and development officer at Allergan.

Given biosimilar applicant experience in navigating the EMA process and the EMA’s high authorization rate, the FDA will need to continue to provide useful guidance and streamline the approval process in order to reduce the imbalance.

Table 1. European Medicines Agency List of Approved Biosimilar Drugs (updated January 24, 2018).

Table 2U.S. Food and Drug Administration List of Approved Biosimilar Drugs (CDER list of licensed biologics updated on December 13, 2017).

Table 3. European Medicines Agency List of Biosimilars Under Evaluation for Marketing Approval (Source: EMA list of applications for new human medicines updated on January 4, 2018).

Table 4Biologics with recent or nearing primary patent expiry in the U.S. that have biosimilars in the regulatory pipeline.