Pfizer’s proposed biosimilar of Amgen’s Epogen® and Johnson & Johnson’s Procrit® (epoetin alfa) is poised to be the first erythropoietin (EPO) biosimilar in the U.S.  FDA staff recommended approval of Pfizer’s product as a biosimilar for the four indications of Epogen/Procrit.  On May 25, 2017, FDA’s advisory committee agreed with that assessment, but FDA did not approve Pfizer’s product following the meeting.  Instead, in a first for biosimilar products, FDA issued a complete response letter in June rejecting Pfizer’s EPO biosimilar application for a second time.  Pfizer revealed that FDA did not approve the application after the advisory committee meeting due to FDA’s concerns with a manufacturing site for the EPO biosimilar.  Pfizer’s product may not be approved, much less launched, this year due to outstanding manufacturing issues.

EPO is a complex and blockbuster biologic product that is used to treat anemia.  It is a glycosylated protein that is produced using genetic engineering techniques in mammalian cells and stimulates production of red blood cells.  Hospira (now a Pfizer company) developed Pfizer’s proposed EPO biosimilar based on Hospira’s Retacrit®, which was approved in Europe in 2007 as a biosimilar to Johnson & Johnson’s Eprex® (epoetin alfa).  The U.S. product uses the same cell line, growth medium and purification as Retacrit. 

Hospira first submitted an abbreviated Biologics License Application (aBLA) for its proposed U.S. EPO biosimilar to FDA in December 2014, which FDA accepted for review in early 2015.  Pfizer acquired Hospira in 2015.  In October 2015, FDA issued its first complete response letter rejecting the application.  FDA’s performance goal is to act on most applications for approval of biosimilar products within a 10-month period.  It met its goal in acting on the application in October 2015, but denied approval of the proposed biosimilar.  Pfizer had indicated that it would resubmit an application to FDA during the first half of 2016, and that it expected FDA to act on the resubmitted application in the second half of 2016.  FDA’s performance goal is to act on most resubmitted applications for biosimilar products within six months. 

Pfizer resubmitted the application in December 2016 and FDA acted within six months.  In May of this year, FDA convened the Oncologic Drugs Advisory Committee.  In its briefing document for the committee, FDA concluded that Pfizer’s proposed product is “highly similar to US-licensed Epogen/Procrit notwithstanding minor differences in clinically inactive components.”  The committee agreed on May 25, voting 14-1 to recommend approval of the first U.S. EPO biosimilar.  One member of the committee voted against approval of the product for two of the four indications, HIV and oncology.  The rest of the committee recommended approval of Pfizer’s product for all four of the indications being sought.  But last month, FDA issued a second complete response letter rejecting Pfizer’s biosimilar application. 

According to Pfizer’s June 22, 2017 press release, this second complete response letter relates to violations noted in FDA’s February 2017 Warning Letter concerning Pfizer’s drug manufacturing facility in McPherson, Kansas.  The facility is the proposed manufacturing site for Pfizer’s EPO biosimilar.  In that Warning Letter, FDA summarized “significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals.”  FDA also noted that it had “cited similar CGMP violations at other facilities in the company’s network.”  In its June 22 press release, Pfizer states that it provided a “corrective and preventative action plan to the FDA in March 2017, and has been diligently working to address the items outlined in the Warning Letter.” 

Pfizer does not mention in the press release when it expects to resolve the manufacturing issues and resubmit its biosimilar application to FDA.  But as discussed at a recent hearing in the patent litigation involving the biosimilar, FDA approval of the EPO biosimilar is unlikely until 2018.  The patent litigation is pending in the District of Delaware before Judge Andrews.  In the district court litigation, Amgen is seeking 180-days’ notice of commercial marketing and to preclude launch of the biosimilar for 180 days after receipt of effective notice.  Pfizer argues that it provided notice in 2015 and that no further notice is necessary prior to launch.