US FDA accepts Roche’s BLA for FDC of Perjeta & Herceptin to treat HER2-positive breast cancer
Roche announced that the US Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) for the fixed-dose combination (FDC) of Perjeta (pertuzumab) and Herceptin (trastuzumab) with hyaluronidase, administered by subcutaneous (SC) injection in combination with intravenous (IV) chemotherapy, for the treatment of eligible patients with HER2-positive breast cancer. The BLA for the FDC is based on results from the phase III FeDeriCa study, which demonstrated non-inferior levels of Perjeta in the blood (pharmacokinetics) and comparable efficacy and safety to standard IV infusions of Perjeta plus Herceptin and chemotherapy.1
“For more than two decades, our medicines have redefined the standard of care for people with HER2-positive breast cancer,” said Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of Global Product Development. “Today’s acceptance builds upon our commitment by potentially offering patients a faster way to administer Perjeta and Herceptin. We’re working with the FDA to bring this treatment option to patients as quickly as possible.”
SC administration of the FDC takes approximately eight minutes for the initial loading dose and approximately five minutes for each subsequent maintenance dose. This is compared to approximately 150 minutes for infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60-150 minutes for subsequent maintenance infusions of the two medicines.
The FeDeriCa study met its primary endpoint, with SC administration of the FDC showing non-inferior levels of Perjeta in the blood during a given dosing interval (Ctrough) when compared to IV administration of Perjeta. A secondary endpoint of non-inferior Ctrough of Herceptin was also met. A non-inferiority endpoint was chosen for the study to ensure that people were receiving sufficient dosing with Perjeta and Herceptin as compared to the established IV doses at the same treatment intervals. In addition, rates of total pathological complete response (pCR), another secondary endpoint, were comparable between the treatment arms. The safety profile of the FDC in combination with chemotherapy was comparable to that of IV administration of Perjeta plus Herceptin and chemotherapy and no new safety signals were identified, including no meaningful difference in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhoea and anaemia.
In previous studies of other SC formulations, SC administration has been shown to be strongly preferred by the majority of patients compared to IV administration of the same medicine, with the most common reason being that administration required less time in the clinic. In the PHranceSCa study, Roche is currently investigating patient preference for SC administration of the FDC compared to standard IV administration of Perjeta and Herceptin in people with HER2-positive early breast cancer (eBC). Interim results of this phase II study will be presented at a future medical meeting.
FeDeriCa is an international, multi-centre, two-arm, randomised, open-label, phase III study evaluating the pharmacokinetics, efficacy and safety of SC injection of the FDC of Perjeta and Herceptin in combination with chemotherapy, compared with standard IV infusions of Perjeta and Herceptin in combination with chemotherapy, in 500 people with HER2-positive eBC who are being treated in the neoadjuvant (before surgery) and adjuvant (after surgery) settings. The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval (Ctrough). Secondary endpoints include safety; minimum levels of Herceptin in the blood during a given dosing interval (Ctrough); and total pCR, meaning there is no tumour tissue detectable in the tissue removed at the time of surgery.
The FDC of Perjeta and Herceptin is a new SC formulation that combines Perjeta and Herceptin with Halozyme Therapeutics’ Enhanze drug delivery technology.
Pertuzumab in the FDC is the same monoclonal antibody as in IV Perjeta, and trastuzumab in the FDC is the same monoclonal antibody as in IV Herceptin. The mechanisms of action of Perjeta and Herceptin are believed to complement each other as both bind to the HER2 receptor, but in different locations. The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of the HER signaling pathways.
The standard IV formulation of Perjeta in combination with IV Herceptin and chemotherapy (the Perjeta-based regimen) is approved in over 100 countries for the treatment of both early and metastatic HER2-positive breast cancer. In the neoadjuvant eBC setting, the Perjeta-based regimen has been shown to almost double the rate of pCR compared to Herceptin and chemotherapy. Additionally, the combination has been shown to significantly reduce the risk of recurrence of invasive disease or death in the adjuvant eBC setting. In the metastatic setting, the combination has shown an unprecedented survival benefit in previously untreated (first-line) patients with HER2-positive metastatic breast cancer.
Halozyme’s Enhanze drug delivery technology may enable and optimise SC drug delivery for appropriate co-administered therapeutics. The technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body – to aid in the dispersion and absorption of other injected therapeutic drugs.
Source:http://www.pharmabiz.com/NewsDetails.aspx?aid=121405&sid=2
“For more than two decades, our medicines have redefined the standard of care for people with HER2-positive breast cancer,” said Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of Global Product Development. “Today’s acceptance builds upon our commitment by potentially offering patients a faster way to administer Perjeta and Herceptin. We’re working with the FDA to bring this treatment option to patients as quickly as possible.”
SC administration of the FDC takes approximately eight minutes for the initial loading dose and approximately five minutes for each subsequent maintenance dose. This is compared to approximately 150 minutes for infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60-150 minutes for subsequent maintenance infusions of the two medicines.
The FeDeriCa study met its primary endpoint, with SC administration of the FDC showing non-inferior levels of Perjeta in the blood during a given dosing interval (Ctrough) when compared to IV administration of Perjeta. A secondary endpoint of non-inferior Ctrough of Herceptin was also met. A non-inferiority endpoint was chosen for the study to ensure that people were receiving sufficient dosing with Perjeta and Herceptin as compared to the established IV doses at the same treatment intervals. In addition, rates of total pathological complete response (pCR), another secondary endpoint, were comparable between the treatment arms. The safety profile of the FDC in combination with chemotherapy was comparable to that of IV administration of Perjeta plus Herceptin and chemotherapy and no new safety signals were identified, including no meaningful difference in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhoea and anaemia.
In previous studies of other SC formulations, SC administration has been shown to be strongly preferred by the majority of patients compared to IV administration of the same medicine, with the most common reason being that administration required less time in the clinic. In the PHranceSCa study, Roche is currently investigating patient preference for SC administration of the FDC compared to standard IV administration of Perjeta and Herceptin in people with HER2-positive early breast cancer (eBC). Interim results of this phase II study will be presented at a future medical meeting.
FeDeriCa is an international, multi-centre, two-arm, randomised, open-label, phase III study evaluating the pharmacokinetics, efficacy and safety of SC injection of the FDC of Perjeta and Herceptin in combination with chemotherapy, compared with standard IV infusions of Perjeta and Herceptin in combination with chemotherapy, in 500 people with HER2-positive eBC who are being treated in the neoadjuvant (before surgery) and adjuvant (after surgery) settings. The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval (Ctrough). Secondary endpoints include safety; minimum levels of Herceptin in the blood during a given dosing interval (Ctrough); and total pCR, meaning there is no tumour tissue detectable in the tissue removed at the time of surgery.
The FDC of Perjeta and Herceptin is a new SC formulation that combines Perjeta and Herceptin with Halozyme Therapeutics’ Enhanze drug delivery technology.
Pertuzumab in the FDC is the same monoclonal antibody as in IV Perjeta, and trastuzumab in the FDC is the same monoclonal antibody as in IV Herceptin. The mechanisms of action of Perjeta and Herceptin are believed to complement each other as both bind to the HER2 receptor, but in different locations. The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of the HER signaling pathways.
The standard IV formulation of Perjeta in combination with IV Herceptin and chemotherapy (the Perjeta-based regimen) is approved in over 100 countries for the treatment of both early and metastatic HER2-positive breast cancer. In the neoadjuvant eBC setting, the Perjeta-based regimen has been shown to almost double the rate of pCR compared to Herceptin and chemotherapy. Additionally, the combination has been shown to significantly reduce the risk of recurrence of invasive disease or death in the adjuvant eBC setting. In the metastatic setting, the combination has shown an unprecedented survival benefit in previously untreated (first-line) patients with HER2-positive metastatic breast cancer.
Halozyme’s Enhanze drug delivery technology may enable and optimise SC drug delivery for appropriate co-administered therapeutics. The technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body – to aid in the dispersion and absorption of other injected therapeutic drugs.
Source:http://www.pharmabiz.com/NewsDetails.aspx?aid=121405&sid=2
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