FDA Recommends Approval of First Biosimilar Application

FDA's Oncologic Drugs Advisory Committee met on Jan. 7, 2015 to review the Biologics License Application (BLA) submitted by Sandoz for a biosimilar version of Amgen's Neupogen (filgrastim). In the meeting, regulators concluded that there were no clinically meaningful differences between Amgen’s Neupogen (filgrastim) and Sandoz’s follow-on biologic version (EP2006) and recommended the agency approve the product. Sandoz already confirmed similarity of their version of filgrastim compared with reference product Neupogen in terms of safety and efficacy in late 2014.

Some issues addressed by the FDA briefing released prior to the decision included the fact that Sandoz used Neupogen approved by the European Union in clinical trials. FDA said six batches of the EU-approved Neupogen manufactured “by the commercial process are lower in protein content than the comparator products and do not meet statistical equivalence.” The dilution was said to have likely occurred at the fill-and-finish stage of manufacturing.

If approved by FDA, Sandoz’s copycat version of filgrastim would be the first official biosimilar approved through the regulatory pathway constructed for these types of biologic medicines. The drug is already approved and marketed as Zarzio in more than 40 countries outside of the United States, although the name in the US may be different.

Umer Raffat, Evercore ISI analyst, wrote in an analyst note that “the key point worth noting is that FDA documents/review and draft questions (which can change) appear to focus on biosimilarity of Zarzio and not the higher bar of interchangeability.” In other words, Raffat and other analysts do not expect FDA to designate Sandoz’s filgrastim as interchangeable. A Novartis spokesperson told Ed Silverman of the Wall Street Journal that the company never submitted an application to FDA seeking an interchangeability status. A request for interchangeability can come later, Sandoz said in a briefing, as “FDA's policy is to require sponsors to first obtain approval as a biosimilar and later apply for interchangeability.”

Another important item to consider is the extrapolation of indications for Neupogen. Although Teva technically had the “first” biosimilar for Neupogen, there was no formal biosimilar pathway in place when the company released Granix (tbo-filgrastim). As a result, Granix was approved for only one indication-reducing neutropenia in non-myeloid malignancy patients receiving myelosuppressive chemotherapy-and was not the indication considered most desirable for Teva. In other words, Granix was ineligible for indication extrapolation through the biologics license agreement pathway. In contrast, through the 351(k) pathway, Sandoz is seeking approval for all five of Neupogen’s indications.

The pathway through which each filgrastim copy was filed may also have an influence on uptake, according to Kate Keeping of Decision Resources. She pointed out in a 2014 blog that the Medicare reimbursement level for Granix may be lower than that of Sandoz’s product and could incentivize the use of Sandoz’s version. “According to the Average Sales Price +6% rule, the value of reimbursement for a biosimilar will be its average selling price plus 6% of the reference brand’s price. However, because Granix was not approved via the biosimilar pathway, reimbursement is calculated as the average selling price plus 6% of its own price, which is approximately 20% less than Neupogen,” Keeping wrote.

A legal wrinkle may dampen the success of Sandoz’s filgrastim, however. As we previously reported, Amgen wants the court to prevent Sandoz from commercially marketing its filgrastim copy and requested an injunction to prevent Sandoz from moving the product through the FDA regulatory process until the company has been granted permission by Amgen to use the license for the medication.

"We are pleased with the ODAC's recommendation to approve our biosimilar filgrastim and we look forward to continuing to work with FDA as it completes its review of our filing," said Mark McCamish, MD, PhD, head of Global Biopharmaceutical and Oncology Injectables Development at Sandoz, in a press release. "We are proud to lead the way in biosimilars globally and believe this positive recommendation brings us one step closer to delivering high-quality biosimilars to patients in the US."

For more detailed information, please read Jill Wechsler's blog on PharmTech.com.