FDA panel backs licensure for epoetin alfa biosimilar

 

A Food and Drug Administration advisory committee voted overwhelmingly in support of licensure for Epoetin Hospira as a biosimilar product to epoetin alfa (Epogen/Procrit) for all approved Epogen/Procrit indications.

Most committee members who voted “yes” said they were hesitant to do so, however, because of safety concerns, particularly in HIV and oncology patients.

The 14-1 vote during the May 25 Oncologic Drugs Advisory Committee meeting specifically addressed whether the totality of evidence presented by Hospira (a Pfizer company), which submitted a biologic licensing application (BLA) for the product, supports licensure. That is, members were asked to consider whether the evidence shows that Epoetin Hospira is highly similar to the reference drug not withstanding minor differences in clinically inactive components. They also considered whether there are clinically meaningful differences between the agent and reference drug and whether the scientific justification is adequate to support licensure for the four proposed indications: treatment of anemia resulting from chronic kidney disease, including in patients on or not on dialysis, to decrease the need for red blood cell transfusion; treatment of anemia resulting from zidovudine administered at no more than 4,200 mg/week in HIV-infected patients with endogenous serum erythropoietin levels of 500 or less mUnits/mL; treatment of anemia in patients with nonmyeloid malignancies in whom anemia results from the effect of concomitant myelosuppressive chemotherapy and in whom, upon initiation, there is a minimum of two additional months of planned chemotherapy; to reduce the need for allogeneic RBC transfusions among patients with perioperative hemoglobin levels greater than 10 to less than 13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery.

“I voted yes. I came in with concerns about the HIV and oncology patients. However, I do believe ... after hearing the justification, that it meets the [FDA regulatory guideline],” said temporary voting member and patient representative Karen E. Arscott, DO, of the Commonwealth Medical College, Scranton, Penn. “I would like to see extensive follow-up in these two population groups,” she said.

The concerns about HIV and oncology patients are related to the potential for immunogenicity-related events. Some members noted that the study populations were likely too small to detect these rare events.

Scott A. Waldman, MD, of Thomas Jefferson University, Philadelphia, also a temporary member, said he voted “yes” because there was “no substantial difference analytically, biologically, or clinically in what was tested.”

“I think the residual uncertainty of immunogenicity and hypersensitivity and the extrapolation across different patient populations will emerge in postmarketing surveillance. I think that’s when we’ll get the clearest picture of whether there really is any uncertainty in how these drugs perform,” he said.

For one member, however, the concerns were enough for a “no” vote.

“The analytical, clinical, and preclinical data support biosimilarity, and I strongly support approval for indications 1 and 4 based on the clinical data ... but I have residual concerns about lack of data, immunogenicity, basic safety data in patients with HIV and cancer and, for that reason, voted no for the broader indication,” said Thomas S. Uldrick, MD, of the HIV & AIDS Malignancy Branch at the Center for Cancer Research, National Cancer Institute, Bethesda, Md.

Gregory J. Riely, MD, of Memorial Sloan-Kettering Cancer Center in New York expressed similar concerns but said he found the data compelling.

“I understand the concerns around immunogenicity for HIV and cancer patients. I was somewhat reassured by the nonclinical data showing an absence of increased immunogenicity for this biosimilar,” he said.

To support its BLA for Epoetin Hospira, Hospira submitted data from four studies comparing it with the U.S.-licensed Epogen/Procrit and presented an analytical biosimilarity assessment and a nonclinical, clinical pharmacology and clinical biosimilarity assessment. The FDA analysis of the data considered chemistry, manufacturing, and controls, as well as pharmacology/toxicology, immunogenicity, clinical pharmacology, and clinical efficacy and safety.

Sumant Ramachandra, MD, of Pfizer Essential Health noted that the company is not currently seeking an interchangeability designation and that, while this is the first application for a biosimilar product to Amgen’s Epogen/Procrit product, which was approved in 1989, a “highly related epoetin product” from Pfizer (Retacrit) has been available in Europe for 9 years, with more than 363,000 patient years of treatment administered.

The demonstration of biosimilarity in the Epoetin Hospira data presented to the FDA, coupled with well-characterized nature of the reference product, “together support extrapolation across all conditions of use for the reference product,” he said, noting that the data demonstrate that the mechanism of action for both the biosimilar and reference product is the same, and that the immunogenicity profiles are consistent.

The FDA assessment of the data led to a similar conclusion that no clinically significant differences were found between the biosimilar and reference product.

Among other concerns expressed by advisory committee members and/or the public were in regard to the extrapolation of data from patients with chronic kidney disease on hemodialysis to other indications (although this is considered acceptable, according to FDA regulations) and to populations that weren’t studied and about the possibility that Epoetin Hospira would be forced on patients inappropriately, despite the fact that Hospira is not seeking an interchangeability designation. Patients and others speaking on behalf of various patient groups and advocacy organizations called for safeguards against such inappropriate substitution.

Acting committee chair, Brian I. Rini, MD, of the Cleveland Clinic Taussig Cancer Clinic, Ohio, said he voted “yes” because the product met all regulatory requirements but agreed that the “need for vigilance is exceedingly important not only for this drug but for all drugs in this circumstance.”

The FDA, which usually follows the recommendations of its advisory committees, will now consider the BLA for Epoetin Hospira.

In a statement released after the vote, Diem Nguyen, Pfizer Essential Health global president, Americas, said the committee’s recommendation for approval “reinforces the potential value of biosimilars in expanding access to additional high-quality treatment options for the patients in the U.S. who need them.”

The advisory committee members were screened and found to have no relevant conflicts of interest.

 

[email protected]

 

A Food and Drug Administration advisory committee voted overwhelmingly in support of licensure for Epoetin Hospira as a biosimilar product to epoetin alfa (Epogen/Procrit) for all approved Epogen/Procrit indications.

Most committee members who voted “yes” said they were hesitant to do so, however, because of safety concerns, particularly in HIV and oncology patients.

The 14-1 vote during the May 25 Oncologic Drugs Advisory Committee meeting specifically addressed whether the totality of evidence presented by Hospira (a Pfizer company), which submitted a biologic licensing application (BLA) for the product, supports licensure. That is, members were asked to consider whether the evidence shows that Epoetin Hospira is highly similar to the reference drug not withstanding minor differences in clinically inactive components. They also considered whether there are clinically meaningful differences between the agent and reference drug and whether the scientific justification is adequate to support licensure for the four proposed indications: treatment of anemia resulting from chronic kidney disease, including in patients on or not on dialysis, to decrease the need for red blood cell transfusion; treatment of anemia resulting from zidovudine administered at no more than 4,200 mg/week in HIV-infected patients with endogenous serum erythropoietin levels of 500 or less mUnits/mL; treatment of anemia in patients with nonmyeloid malignancies in whom anemia results from the effect of concomitant myelosuppressive chemotherapy and in whom, upon initiation, there is a minimum of two additional months of planned chemotherapy; to reduce the need for allogeneic RBC transfusions among patients with perioperative hemoglobin levels greater than 10 to less than 13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery.

“I voted yes. I came in with concerns about the HIV and oncology patients. However, I do believe ... after hearing the justification, that it meets the [FDA regulatory guideline],” said temporary voting member and patient representative Karen E. Arscott, DO, of the Commonwealth Medical College, Scranton, Penn. “I would like to see extensive follow-up in these two population groups,” she said.

The concerns about HIV and oncology patients are related to the potential for immunogenicity-related events. Some members noted that the study populations were likely too small to detect these rare events.

Scott A. Waldman, MD, of Thomas Jefferson University, Philadelphia, also a temporary member, said he voted “yes” because there was “no substantial difference analytically, biologically, or clinically in what was tested.”

“I think the residual uncertainty of immunogenicity and hypersensitivity and the extrapolation across different patient populations will emerge in postmarketing surveillance. I think that’s when we’ll get the clearest picture of whether there really is any uncertainty in how these drugs perform,” he said.

For one member, however, the concerns were enough for a “no” vote.

“The analytical, clinical, and preclinical data support biosimilarity, and I strongly support approval for indications 1 and 4 based on the clinical data ... but I have residual concerns about lack of data, immunogenicity, basic safety data in patients with HIV and cancer and, for that reason, voted no for the broader indication,” said Thomas S. Uldrick, MD, of the HIV & AIDS Malignancy Branch at the Center for Cancer Research, National Cancer Institute, Bethesda, Md.

Gregory J. Riely, MD, of Memorial Sloan-Kettering Cancer Center in New York expressed similar concerns but said he found the data compelling.

“I understand the concerns around immunogenicity for HIV and cancer patients. I was somewhat reassured by the nonclinical data showing an absence of increased immunogenicity for this biosimilar,” he said.

To support its BLA for Epoetin Hospira, Hospira submitted data from four studies comparing it with the U.S.-licensed Epogen/Procrit and presented an analytical biosimilarity assessment and a nonclinical, clinical pharmacology and clinical biosimilarity assessment. The FDA analysis of the data considered chemistry, manufacturing, and controls, as well as pharmacology/toxicology, immunogenicity, clinical pharmacology, and clinical efficacy and safety.

Sumant Ramachandra, MD, of Pfizer Essential Health noted that the company is not currently seeking an interchangeability designation and that, while this is the first application for a biosimilar product to Amgen’s Epogen/Procrit product, which was approved in 1989, a “highly related epoetin product” from Pfizer (Retacrit) has been available in Europe for 9 years, with more than 363,000 patient years of treatment administered.

The demonstration of biosimilarity in the Epoetin Hospira data presented to the FDA, coupled with well-characterized nature of the reference product, “together support extrapolation across all conditions of use for the reference product,” he said, noting that the data demonstrate that the mechanism of action for both the biosimilar and reference product is the same, and that the immunogenicity profiles are consistent.

The FDA assessment of the data led to a similar conclusion that no clinically significant differences were found between the biosimilar and reference product.

Among other concerns expressed by advisory committee members and/or the public were in regard to the extrapolation of data from patients with chronic kidney disease on hemodialysis to other indications (although this is considered acceptable, according to FDA regulations) and to populations that weren’t studied and about the possibility that Epoetin Hospira would be forced on patients inappropriately, despite the fact that Hospira is not seeking an interchangeability designation. Patients and others speaking on behalf of various patient groups and advocacy organizations called for safeguards against such inappropriate substitution.

Acting committee chair, Brian I. Rini, MD, of the Cleveland Clinic Taussig Cancer Clinic, Ohio, said he voted “yes” because the product met all regulatory requirements but agreed that the “need for vigilance is exceedingly important not only for this drug but for all drugs in this circumstance.”

The FDA, which usually follows the recommendations of its advisory committees, will now consider the BLA for Epoetin Hospira.

In a statement released after the vote, Diem Nguyen, Pfizer Essential Health global president, Americas, said the committee’s recommendation for approval “reinforces the potential value of biosimilars in expanding access to additional high-quality treatment options for the patients in the U.S. who need them.”

The advisory committee members were screened and found to have no relevant conflicts of interest.

 

[email protected]

 

A Food and Drug Administration advisory committee voted overwhelmingly in support of licensure for Epoetin Hospira as a biosimilar product to epoetin alfa (Epogen/Procrit) for all approved Epogen/Procrit indications.

Most committee members who voted “yes” said they were hesitant to do so, however, because of safety concerns, particularly in HIV and oncology patients.

The 14-1 vote during the May 25 Oncologic Drugs Advisory Committee meeting specifically addressed whether the totality of evidence presented by Hospira (a Pfizer company), which submitted a biologic licensing application (BLA) for the product, supports licensure. That is, members were asked to consider whether the evidence shows that Epoetin Hospira is highly similar to the reference drug not withstanding minor differences in clinically inactive components. They also considered whether there are clinically meaningful differences between the agent and reference drug and whether the scientific justification is adequate to support licensure for the four proposed indications: treatment of anemia resulting from chronic kidney disease, including in patients on or not on dialysis, to decrease the need for red blood cell transfusion; treatment of anemia resulting from zidovudine administered at no more than 4,200 mg/week in HIV-infected patients with endogenous serum erythropoietin levels of 500 or less mUnits/mL; treatment of anemia in patients with nonmyeloid malignancies in whom anemia results from the effect of concomitant myelosuppressive chemotherapy and in whom, upon initiation, there is a minimum of two additional months of planned chemotherapy; to reduce the need for allogeneic RBC transfusions among patients with perioperative hemoglobin levels greater than 10 to less than 13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery.

“I voted yes. I came in with concerns about the HIV and oncology patients. However, I do believe ... after hearing the justification, that it meets the [FDA regulatory guideline],” said temporary voting member and patient representative Karen E. Arscott, DO, of the Commonwealth Medical College, Scranton, Penn. “I would like to see extensive follow-up in these two population groups,” she said.

The concerns about HIV and oncology patients are related to the potential for immunogenicity-related events. Some members noted that the study populations were likely too small to detect these rare events.

Scott A. Waldman, MD, of Thomas Jefferson University, Philadelphia, also a temporary member, said he voted “yes” because there was “no substantial difference analytically, biologically, or clinically in what was tested.”

“I think the residual uncertainty of immunogenicity and hypersensitivity and the extrapolation across different patient populations will emerge in postmarketing surveillance. I think that’s when we’ll get the clearest picture of whether there really is any uncertainty in how these drugs perform,” he said.

For one member, however, the concerns were enough for a “no” vote.

“The analytical, clinical, and preclinical data support biosimilarity, and I strongly support approval for indications 1 and 4 based on the clinical data ... but I have residual concerns about lack of data, immunogenicity, basic safety data in patients with HIV and cancer and, for that reason, voted no for the broader indication,” said Thomas S. Uldrick, MD, of the HIV & AIDS Malignancy Branch at the Center for Cancer Research, National Cancer Institute, Bethesda, Md.

Gregory J. Riely, MD, of Memorial Sloan-Kettering Cancer Center in New York expressed similar concerns but said he found the data compelling.

“I understand the concerns around immunogenicity for HIV and cancer patients. I was somewhat reassured by the nonclinical data showing an absence of increased immunogenicity for this biosimilar,” he said.

To support its BLA for Epoetin Hospira, Hospira submitted data from four studies comparing it with the U.S.-licensed Epogen/Procrit and presented an analytical biosimilarity assessment and a nonclinical, clinical pharmacology and clinical biosimilarity assessment. The FDA analysis of the data considered chemistry, manufacturing, and controls, as well as pharmacology/toxicology, immunogenicity, clinical pharmacology, and clinical efficacy and safety.

Sumant Ramachandra, MD, of Pfizer Essential Health noted that the company is not currently seeking an interchangeability designation and that, while this is the first application for a biosimilar product to Amgen’s Epogen/Procrit product, which was approved in 1989, a “highly related epoetin product” from Pfizer (Retacrit) has been available in Europe for 9 years, with more than 363,000 patient years of treatment administered.

The demonstration of biosimilarity in the Epoetin Hospira data presented to the FDA, coupled with well-characterized nature of the reference product, “together support extrapolation across all conditions of use for the reference product,” he said, noting that the data demonstrate that the mechanism of action for both the biosimilar and reference product is the same, and that the immunogenicity profiles are consistent.

The FDA assessment of the data led to a similar conclusion that no clinically significant differences were found between the biosimilar and reference product.

Among other concerns expressed by advisory committee members and/or the public were in regard to the extrapolation of data from patients with chronic kidney disease on hemodialysis to other indications (although this is considered acceptable, according to FDA regulations) and to populations that weren’t studied and about the possibility that Epoetin Hospira would be forced on patients inappropriately, despite the fact that Hospira is not seeking an interchangeability designation. Patients and others speaking on behalf of various patient groups and advocacy organizations called for safeguards against such inappropriate substitution.

Acting committee chair, Brian I. Rini, MD, of the Cleveland Clinic Taussig Cancer Clinic, Ohio, said he voted “yes” because the product met all regulatory requirements but agreed that the “need for vigilance is exceedingly important not only for this drug but for all drugs in this circumstance.”

The FDA, which usually follows the recommendations of its advisory committees, will now consider the BLA for Epoetin Hospira.

In a statement released after the vote, Diem Nguyen, Pfizer Essential Health global president, Americas, said the committee’s recommendation for approval “reinforces the potential value of biosimilars in expanding access to additional high-quality treatment options for the patients in the U.S. who need them.”

The advisory committee members were screened and found to have no relevant conflicts of interest.

 

[email protected]