John P. Kennedy
Epoetin alfa-epbx (Retacrit), the biosimilar to epoetin alfa (Procrit/Epogen) has been launched in the United States at a significant discount, according to Pfizer, the developer of the injectable.1
The shipment of the biosimilar to wholesalers throughout the United States began on November 12, 2018.
“We are delighted to introduce our third biosimilar in the United States,” said John P. Kennedy, general manager of US Biosimilars at Pfizer Essential Health, in a recent statement. “Pfizer is committed to fostering a sustainable marketplace for biosimilars and advocates for policies that bring these important medicines to patients and physicians as quickly as possible.”
Prior to this announcement, on May 15, 2018, the FDA approved the biosimilar to be used as a treatment for anemia caused by chronic kidney disease, chemotherapy, or the use of zidovudine in patients with HIV infection.2
Epoetin alfa-epbx is also indicated for use prior to and following surgery to decrease the likelihood that patients will need a red blood cell transfusion due to blood loss from surgery.
The manufacturer of the biosimilar, Hospira, a Pfizer company, submitted the biologics license application (BLA) based on data yielded from the 2 single-center, randomized, open-label EPOE-12-02 and EPOE-14-01 studies.
The first study was designed to establish the pharmacokinetics (PK) and pharmacodynamics (PD; reticulocyte count) of the biosimilar following a single subcutaneous dose of 100 u/kg in healthy participants (n = 81). The investigators compared the biosimilar data with that of epoetin alfa.
Investigators found that the biosimilar met the prespecified acceptance criteria for similarity, the geometric mean of AUC0-120h
(1.06 mIU-h/mL; 90% CI, 1.01-1.11), AUC0-INF
(1.03 mIU-h/mL; 90% CI, 0.97-1.09), and CMAX
(1.09 mIU-h/mL; 90% CI, 1.01-1.18). The same was true of PD for AUEC0-456h
(1.01%-h; 90% CI, 0.98-1.05) and EMAX
(1.02%-h; 90% CI, 0.99-1.05).
The second study, EPOE-14-01, aimed to determine the drug’s PK and PD (hemoglobin level) after multiple doses of subcutaneous 100 u/kg of the biosimilar 3 times weekly for the duration of 4 weeks in health participants (n = 129). Again, these data were compared with data associated with epoetin alfa.
This study also met prespecified acceptance criteria for PD similarity of geometric mean of hemoglobin level AEUC 0-28d
(1.00 g-h/dL; 90% CI, 0.99-1.02) and EMAX
(1.00 g/dL; 90% CI, 0.99-1.02).
The FDA’s Oncologic Drugs Advisory Committee voted 14 to 1 in favor of the approval of the BLA for the biosimilar in May 2017. At that time, the committee reported that the analytical similarity data supported the conclusion that, overall, epoetin alfa-epbx was “highly similar to US-licensed Epogen/Procrit, notwithstanding minor differences in clinically inactive components.” They added that “there were no clinically relevant differences” in the data associated with PK, PD, safety, efficacy, and immunogenicity between the two drugs.
Not long afterwards, however, the FDA issued a complete response letter to Hospira expressing concerns regarding manufacturing the biosimilar at the company’s facility based in McPherson, Kansas. Particular issues identified by the FDA included: in-process specifications, failure to follow procedures developed to prevent contamination of products, and lack of appropriate sampling plans for analytical and inspection activities.
However, Pfizer emphasized that these concerns were not specifically related to epoetin alfa-epbx, and, in an attempt to address the FDA’s concerns, the company submitted a corrective and preventative action plan in March 2017.
Epoetin alfa-epbx will now be introduced to the market at a substantial discount at a Wholesale Acquisition Cost (WAC) of $11.03 per 1000 units/mL, which is 57.1% below the WAC of Procrit ($25.72 per 1000 units/mL), and 33.5% below the WAC of its reference product, Epogen ($16.58 per 1000 units/mL).
Epoetin alfa-epbx has been granted 2 unique assigned Q codes from the Centers for Medicare and Medicaid Services: Q5105 for End-Stage Renal Disease (ESRD) and Q5106 for non-ESRD. Under the hospital outpatient prospective payment system, epoetin alfa-epbx qualifies for pass-through status.
- Pfizer. Pfizer introduced biosimilar Retacrit (epoetin alfa-epbx) injection in the US at a substantial discount. Published November 14, 2018.
- Pfizer. Pfizer’s biosimilar RETACRIT® (epoetin alfa-epbx) approved by U.S. FDA. Published May 15, 2018. https://bit.ly/2Pd4J3L. Accessed November 14, 2018.