More biosimilars reach the market in efforts to improve access and cut costs

Epoetin alfa-epbx

Epoetin alfa-epbx was evaluated in 2 clinical trials in healthy individuals. The EPOE-12-02 trial established the PK and PD following a single subcutaneous dose of 100 U/kg in 81 participants. The EPOE-14-1 study was designed to determine the PK and PD of multiple doses of subcutaneous 100 U/kg 3 times weekly for 3 weeks in 129 participants. Both studies met prespecified criteria for PK and PD similarity to US-approved epoetin alfa, including geometric mean of area under the curve (AUC)0-120h, AUC0-inf, C_max (maximum serum concentration achieved by a drug in a specified area of the body) and E_max (maximum response achievable for a drug dose).

Evidence of efficacy and safety were also evaluated using pooled data from EPOE-10-13 and EPOE-10-01, conducted in patients with chronic kidney disease, which was considered the most sensitive population in which to evaluate clinically meaningful differences between the biosimilar and reference product.^8,9

There were no clinically meaningful differences in efficacy and a similar adverse event profile. The most common side effects include high blood pressure, joint pain, muscle spasm, fever, dizziness, respiratory infection, and cough, among others.

The recommended dose of epoetin alfa-epbx, which is marketed as Retacrit, is 40,000 Units weekly or 150 U/kg 3 times weekly in adults and 600 U/kg intravenously weekly in pediatric patients aged 5 years or younger. Epoetin alfa-epbx comes with a boxed warning to alert health care providers to the increased risks of death, heart problems, stroke, and tumor growth, or recurrence. The prescribing information also details warnings and precautions relating to these risks, as well as hypertension, seizures, lack or loss of hemoglobin response, pure red cell aplasia, serious allergic reactions, and severe cutaneous reactions.⁹

Blood pressure should be appropriately controlled before treatment initiation, treatment should be reduced or withheld if it becomes uncontrollable, and patients should be advised of the importance of compliance with anti-hypertensive medication and dietary restrictions. Patients should be monitored closely for premonitory neurologic symptoms and advised to contact their provider in the event of new-onset seizures, premonitory symptoms, or change in seizure frequency.

The prescribing information has dosing recommendations for lack or loss of hemoglobin response to epoetin alfa-epbx. If severe anemia or low reticulocyte count occur, treatment should be withheld and patients evaluated for neutralizing antibodies to erythropoietin and, in the event that PRCA is confirmed, treatment should be permanently discontinued. Treatment should be immediately and permanently discontinued for serious allergic reactions or severe cutaneous reactions.