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A biologics license application has been submitted to the FDA for the approval of F-627 as a treatment option for patients with breast cancer who have chemotherapy-induced neutropenia.
A biologics license application has been submitted to the FDA for the approval of F-627 (Ryzneuta; formerly efbemalenograstim alpha) as a treatment option for patients with breast cancer who have chemotherapy-induced neutropenia, according to an announcement from Evive Biotech.1
The submission follows the completion of two phase 3 clinical trials examining the agent (NCT03252431 and NCT02872103) which both met their primary and secondary end points and showed strong and durable activity in this population.
“This is a significant milestone for Evive and demonstrates our full in-house capability to develop a novel biological drug from laboratory bench to global market launch,” Dr. Jubo Liu, chief executive officer of Evive Biotech, stated in a press release. “With this submission, we are looking forward to working with our partners to make [F-627] accessible to patients suffering from chemotherapy-induced neutropenia.”
F-627 is a recombinant fusion protein that contains granulocyte colony–stimulating factor at the amino terminal and human IgG2-Fc fragment at the carboxyl terminal. The protein is expressed in Chinese Hamster Ovary cells and it exists as a dimer with 2 molecules of rhG-CSF that are covalently linked with disulfide bonds made between the Fc fragment of the molecule.
F-627 triggers white blood cell production, which assists the immune system in fighting infection. Many patients who receive chemotherapy experience a drop in their white blood cell count; the protein was developed to boost those counts and enhance immune system response.
In the first multicenter, single-dose, open-label, phase 3 trial, investigators examined the safety and efficacy of the agent in patients with breast cancer who were receiving treatment with chemotherapy.2,3 To be eligible for enrollment, patients needed to have stage I-III invasive breast cancer who were to receive either neoadjuvant or adjuvant myelotoxic TC chemotherapy comprised of 75 mg/m2 of docetaxel and 600 mg/m2 of cyclophosphamide.
Twenty-four hours after chemotherapy completion in each cycle, patients in arm A were given F-627 at a fixed dose of 20 mg on day 2 of each 4 chemotherapy cycles, while those in arm B received pegfilgrastim (Neulasta) at a fixed dose of 6 mg on day 2 of each 4 chemotherapy cycles. Participants were randomized in a 1:1 fashion.
In the other phase 3 trial, investigators set out to evaluate the safety and efficacy of once-per-cycle F-627 in patients with stage II-IV breast cancer who were receiving myelotoxic TA chemotherapy comprised of docetaxel at 75 mg/m2 and doxorubicin at 60 mg/m2.4
To be eligible for enrollment, patients had to aged 18 years or older but under the age of 75 years, have stage II-IV disease, be scheduled to receive 4 cycles of TA chemotherapy, have an ECOG performance status of 0 to 2 and a white blood cell count of at least 4.0 x 109/L, hemoglobin of at least 11.5 g/dL, and a platelet count of at least 150 x 109/L.
Here, F-627 or placebo were administered subcutaneously 24 hours following chemotherapy in each 21-day cycle of chemotherapy treatment. The primary outcome measure for this trial was duration in days of grade 4 neutropenia observed in chemotherapy cycle 1 with F-627 vs placebo, while secondary measures included duration of grade 4 neutropenia for chemotherapy cycles 2, 3, and 4, and over all cycles; duration in days of grade 2, grade 3, and 4 neutropenia over all cycles; and others.
Previously, the agent was found to significantly reduce the duration of grade 4 neutropenia in chemotherapy cycle 1 (P <.0001) among 122 patients with stage II-IV breast cancer who were receiving myelotoxic chemotherapy, according to data presented at the 2018 San Antonio Breast Cancer Symposium.5 The mean treatment difference was 2.8 days, with 1.1 days in the investigative arm and 3.9 days in the control arm. F-627 also resulted in a lower incidence and shorter duration of grade 2, 3, and 4 neutropenia.
F-627 also significantly reduced incidence of febrile neutropenia compared with the control in cycle 1, at 4.8% and 28.2%, respectively (P <.0016). Additionally, F-627 resulted in lower rates of antibiotic and pain medication use.
The agent was found to be safe and well tolerated. No deaths or injection site reactions were reported with F-627. Moreover, less gastrointestinal adverse effects were reported in the investigative arm vs the placebo arm. During cycle 1, the most frequently reported treatment-emergent toxicities were leukopenia, anemia, thrombocytopenia, nausea, and alopecia.