BALTIMORE––Making a generic drug is easy compared to developing a biosimilar compound, said David Goldsmith, MD, president and senior consultant of Goldsmith Pharmacovigilance and Systems. He, along with Ali McBride, PharmD, clinical coordinator for hematology/oncology at the University of Arizona Cancer Center, walked through the steps of how biosimilars are tested and developed during a symposium held this past week at the Renal Physicians Association’s annual meeting here.

The symposium was sponsored by Hospira, who is currently awaiting U.S. Food and Drug Administration review of its biosimilar Retacrit, a drug that would compete with Amgen’s epoetin alfa and Janssen’s Procrit. Hospira submitted the application last December, making it the fourth company to announce submission of a biosimilar application to the FDA. The drugmaker said it expects FDA notification of acceptance of the submission within 60 days of filing.

The FDA has committed for this fiscal year to act on at least 80% of biosimilar applications within 10 months, according to a Jan. 20 article in FDA News. An FDA’s Oncologic Drugs Advisory Committee voted unanimously recently to recommend approval of Sandoz’s Zarxio, a biosimilar to Amgen’s Neupogen (filgrastim).
While still in its infancy in the U.S., biosimilars have been marketed in Europe for a number of years. Hospira has products in Australian and European markets, including Retacrit, which Hospira launched in Europe in 2008 and Australia in 2011.

Goldsmith and McBride both agreed that the biosimilar path is a complicated one. Unlike generic manufacturers, biosimilar pharmaceutical companies have to notify the company they will be directly competing against that they are developing a similar drug to their original biologic.

But biosimilar companies point to the high cost of biologics to help justify their pursuit: global biological sales are projected to be $221 billion in 2017, up from just $46 billion in 2002. In 2010, eight of the 10 highest expenditure drugs were biologics, accounting for more than $8 billion in Medicare Part B spending. Epoetin for patients on dialysis was at the top of the list, with $2 billion spent on the drug by Medicare in 2010.

Patents losing clout

Part of the pursuit of Amgen’s Epogen by biosimilar manufacturers lies in the upcoming expiration of patents owned by the company.  The FDA has set up requirements for biosimilar manufacturers for testing and validation studies of their drug “to ensure the quality, safety, and efficacy of a biologic.” Such requirements are already set up in Europe for drug manufacturers, including tests to determine comparability to protein structure and product quality to the biologic; in vivo and in vitro assays to confirm functional biosimilarity; preregistration studies to compare efficacy between the biosimilar and the biologic drug, and comparative phase 3 studies of “head-to-head” biosimilar versus the reference biologic studies with patients.

To date, there are 17 biosimilars approved in Europe by the European Medicines Agency, including three Epoetin alpha products.

The FDA has been developing guidelines for the approval of biosimilars since March 2010, and came out with final regulations in September 2014. The overall approach from the FDA will focus on a “totality of evidence” approach, which will lessen the need for extensive animal and clinical testing.

Ultimately, biosimilars could be a significant part of the pharmaceutical market in the near future. The Institute for Healthcare Informatics estimated that manufacturers spent $92 billion on biologics in 2013, up 9.6% from 2012.  But an IMS Health report released in December 2011 predicted that by 2020, the U.S. biosimilar market may be as large as $25 billion. Various sources estimate that biosimilars could save the government $25 billion over the next 10 years.