Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapy
Abstract Background Chemotherapy-induced neutropenia is a common result of myelosuppressive chemotherapy treatment. Infections such as febrile neutropenia (FN) are sensitive to the duration of neutropenia as well as the depth of absolute neutrophil count (ANC) at nadir. Filgrastim, a granulocyte col...
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | Experimental Hematology & Oncology |
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| Online Access: | http://link.springer.com/article/10.1186/s40164-018-0114-9 |
| _version_ | 1818138974827315200 |
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| author | Kalpna Desai Priya Misra Sanyukta Kher Nirmesh Shah |
| author_facet | Kalpna Desai Priya Misra Sanyukta Kher Nirmesh Shah |
| author_sort | Kalpna Desai |
| collection | DOAJ |
| description | Abstract Background Chemotherapy-induced neutropenia is a common result of myelosuppressive chemotherapy treatment. Infections such as febrile neutropenia (FN) are sensitive to the duration of neutropenia as well as the depth of absolute neutrophil count (ANC) at nadir. Filgrastim, a granulocyte colony stimulating factor (G-CSF), can stimulate the function of mature neutrophils. Pegfilgrastim, a long-acting form of filgrastim, has been shown to reduce FN to a greater extent compared to filgrastim. G-CSF agents have been recommended for prophylactic administration with chemotherapy. Apotex developed a proposed pegfilgrastim biosimilar. This study was conducted to confirm that no clinically meaningful efficacy or safety differences exist between Apotex’s proposed biosimilar and its reference product. Methods 589 breast cancer patients were randomized and dosed with the proposed pegfilgrastim biosimilar, US-licensed pegfilgrastim reference product, or EU-approved pegfilgrastim reference product. The primary endpoint assessed was the duration of severe neutropenia (DSN) and secondary endpoints included rate of FN and ANC nadir. Results Data showed that the mean DSN, the primary endpoint measured, was comparable across all three treatments. The As Treated arm had a 95% confidence interval within the equivalence range for the proposed pegfilgrastim biosimilar with the US-licensed and EU-approved pegfilgrastim reference products. Secondary endpoints, which included depth and peak of ANC nadir, time to ANC recovery post-nadir and rates of FN, also showed similarity between the three different treatment groups. The adverse event incidence was similar across treatment arms and there were no unexpected safety events. Conclusions Overall, these results show that the proposed pegfilgrastim biosimilar is similar to Amgen’s US-licensed and EU-approved pegfilgrastim reference products with regard to the clinical efficacy and safety endpoints assessed. Trial registration EMA: European Union Clinical Trials Register: (https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002678-21) Eudract # 2011-002678-21 Registered: 01/10/2012 |
| first_indexed | 2024-12-11T10:20:43Z |
| format | Article |
| id | doaj.art-058efc7f899c4f45b9fb5806cf474b8d |
| institution | Directory Open Access Journal |
| issn | 2162-3619 |
| language | English |
| last_indexed | 2024-12-11T10:20:43Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj.art-058efc7f899c4f45b9fb5806cf474b8d2022-12-22T01:11:26ZengBMCExperimental Hematology & Oncology2162-36192018-09-017111110.1186/s40164-018-0114-9Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapyKalpna Desai0Priya Misra1Sanyukta Kher2Nirmesh Shah3Preclinical and Clinical Programs, ApobiologixPreclinical and Clinical Programs, ApobiologixRegulatory Affairs, ApobiologixMedical Affairs, ApobiologixAbstract Background Chemotherapy-induced neutropenia is a common result of myelosuppressive chemotherapy treatment. Infections such as febrile neutropenia (FN) are sensitive to the duration of neutropenia as well as the depth of absolute neutrophil count (ANC) at nadir. Filgrastim, a granulocyte colony stimulating factor (G-CSF), can stimulate the function of mature neutrophils. Pegfilgrastim, a long-acting form of filgrastim, has been shown to reduce FN to a greater extent compared to filgrastim. G-CSF agents have been recommended for prophylactic administration with chemotherapy. Apotex developed a proposed pegfilgrastim biosimilar. This study was conducted to confirm that no clinically meaningful efficacy or safety differences exist between Apotex’s proposed biosimilar and its reference product. Methods 589 breast cancer patients were randomized and dosed with the proposed pegfilgrastim biosimilar, US-licensed pegfilgrastim reference product, or EU-approved pegfilgrastim reference product. The primary endpoint assessed was the duration of severe neutropenia (DSN) and secondary endpoints included rate of FN and ANC nadir. Results Data showed that the mean DSN, the primary endpoint measured, was comparable across all three treatments. The As Treated arm had a 95% confidence interval within the equivalence range for the proposed pegfilgrastim biosimilar with the US-licensed and EU-approved pegfilgrastim reference products. Secondary endpoints, which included depth and peak of ANC nadir, time to ANC recovery post-nadir and rates of FN, also showed similarity between the three different treatment groups. The adverse event incidence was similar across treatment arms and there were no unexpected safety events. Conclusions Overall, these results show that the proposed pegfilgrastim biosimilar is similar to Amgen’s US-licensed and EU-approved pegfilgrastim reference products with regard to the clinical efficacy and safety endpoints assessed. Trial registration EMA: European Union Clinical Trials Register: (https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002678-21) Eudract # 2011-002678-21 Registered: 01/10/2012http://link.springer.com/article/10.1186/s40164-018-0114-9BiosimilarPegfilgrastimChemotherapy-induced neutropeniaSevere neutropeniaFebrile neutropeniaAbsolute neutrophil count |
| spellingShingle | Kalpna Desai Priya Misra Sanyukta Kher Nirmesh Shah Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapy Experimental Hematology & Oncology Biosimilar Pegfilgrastim Chemotherapy-induced neutropenia Severe neutropenia Febrile neutropenia Absolute neutrophil count |
| title | Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapy |
| title_full | Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapy |
| title_fullStr | Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapy |
| title_full_unstemmed | Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapy |
| title_short | Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapy |
| title_sort | clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim a 3 way randomized equivalence study for a proposed biosimilar pegfilgrastim versus us licensed and eu approved reference products in breast cancer patients receiving myelosuppressive chemotherapy |
| topic | Biosimilar Pegfilgrastim Chemotherapy-induced neutropenia Severe neutropenia Febrile neutropenia Absolute neutrophil count |
| url | http://link.springer.com/article/10.1186/s40164-018-0114-9 |
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