Ortho Biotech Statement on U.S. Food and Drug Administration Oncologic Drugs Advisory Committee Vote
Ortho Biotech is concerned by the Advisory Committee’s recommendations to restrict access to erythropoiesis-stimulating agents (ESAs) for chemotherapy-induced anemia (CIA) in patients with metastatic breast and head and neck cancer, and patients treated with curative intent. The company believes that fully informed patients and their physicians should have the choice to use this important medication, which is the only therapeutic alternative to blood transfusion.
“Over the past several months, the company provided the FDA with substantial new data that give important insight into the safety of ESAs,” said Jay Siegel, M.D., Group President, Research & Development. “We hope that the FDA will now take time to review this substantial body of data before reaching its final decision.”
The FDA has not yet reviewed new or follow-up survival data accounting for approximately 50 percent of the 7,444 patients in the company’s database. The totality of available data support continuing the option to use ESAs according to the label in patients with chemotherapy-induced anemia (CIA).
Out of a total of 59 controlled studies with survival data, the FDA has focused on eight studies of concern. All eight studies researched investigational uses of the drug, and the PROCRIT® (Epoetin alfa) label contains specific warnings against such uses.
In addition, a representative of the Cochrane Collaboration who attended the meeting confirmed that the group is about to generate important new analyses regarding the safety of ESA use in CIA. The FDA should consider these analyses before making its final decision.
The current product labeling prominently reflects all known risks of ESAs, including thrombovascular events (TVEs). TVEs are a plausible explanation for increased mortality observed in studies with high hemoglobin (Hb) targets. When ESA use is targeted to Hb higher than 12 grams per deciliter of blood (g/dL), the risk is unacceptably increased.
Ortho Biotech will continue to evaluate and minimize risk of ESAs within the labeled treatment setting. We remain committed to continuing to educate healthcare professionals and patients regarding the appropriate use of PROCRIT®.
About PROCRIT® (Epoetin alfa)
PROCRIT® is used for the treatment of anemia in patients with most types of cancer receiving chemotherapy, with chronic renal failure who are on dialysis and those who are not on dialysis, who are being treated with zidovudine for HIV infection, and to reduce the need for transfusion in anemic patients who are scheduled for elective noncardiac, nonvascular surgery. Depending on the country in which Epoetin alfa is marketed, these indications may differ.
Important U.S. Safety Information for PROCRIT®
Boxed WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION
Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.
* ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of greater than or equal to 12 g/dL.
* The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of -12 g/dL.
* To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions.
* Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
* Discontinue following the completion of a chemotherapy course.
Perisurgery: PROCRIT® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.
PROCRIT® is contraindicated in patients with uncontrolled hypertension or with known hypersensitivity to albumin (human) or mammalian cell-derived products.
Additional Important Safety Information
* The dose of PROCRIT® should be titrated for each patient to achieve and maintain the following hemoglobin levels:
o Chronic renal failure patients - hemoglobin levels between 10 to 12 g/dL. If a patient does not attain hemoglobin levels of 10 to 12 g/dL despite 12 weeks of appropriate PROCRIT® therapy, see DOSAGE and ADMINISTRATION in the PROCRIT® Prescribing Information. Cancer or HIV patients - the lowest hemoglobin level sufficient to avoid transfusion and not to exceed 12 g/dL.
o Monitor hemoglobin regularly during therapy, more frequently following a dosage adjustment or until hemoglobin becomes stable.
* Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients with chronic renal failure receiving PROCRIT® by subcutaneous administration. If any patient develops a sudden loss of response to PROCRIT®, accompanied by severe anemia and low reticulocyte count, and anti-erythropoietin antibody-associated anemia is suspected, withhold PROCRIT® and other erythropoietic proteins. Contact ORTHO BIOTECH (1-888-2ASKOBI or1-888-227-5624) to perform assays for binding and neutralizing antibodies. If erythropoietin antibody-mediated anemia is confirmed, PROCRIT® should be permanently discontinued and patients should not be switched to other erythropoietic proteins.
* The safety and efficacy of PROCRIT® therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes or hypercoagulable disorders).
* In some female patients, menses have resumed following PROCRIT® therapy; the possibility of pregnancy should be discussed and the need for contraception evaluated.
* Prior to and regularly during PROCRIT® therapy monitor iron status; transferrin saturation should be greater than or equal to 20% and ferritin should be greater than or equal to 100 ng/mL. During therapy absolute or functional iron deficiency may develop and all patients will eventually require supplemental iron to adequately support erythropoiesis stimulated by PROCRIT® .
* During PROCRIT® therapy, blood pressure should be monitored carefully and aggressively managed, particularly in patients with an underlying history of hypertension or cardiovascular disease.
* In studies, the most common side effects included fever (pyrexia), diarrhea, nausea, vomiting, swelling of hands or feet (edema), lack or loss of strength or weakness (asthenia, fatigue), shortness of breath, high blood pressure, headache, joint pain (arthralgias), abnormal skin sensations (as tingling or tickling or itching or burning; paresthesia), rash, constipation and upper respiratory infection.
Please visit www.procrit.com for the full Prescribing Information, including the Boxed WARNINGS.
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