FDA Approves Eflapegrastim for Chemo-Induced Neutropenia

FDA

The FDA has approved eflapegrastim-xnst (Rolvedon) injection to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia.¹

The approval was supported by data from the phase 3 ADVANCE (NCT02643420) and RECOVER (NCT02953340) trials, where eflapegrastim demonstrated the pre-specified hypothesis of non-inferiority vs pegfilgrastim (Neulasta) in mean duration of severe neutropenia with a similar safety profile to pegfilgrastim.

“[Eflapegrastim's] approval marks Spectrum’s transformation to a commercial-stage company with the opportunity to compete in a $2 billion dollar market, and offers a unique value proposition,” Tom Riga, president and chief executive officer of Spectrum Pharmaceuticals, stated in a news release. “This approval is a significant milestone for our development team and collaboration with Hanmi Pharmaceutical. On behalf of Spectrum, I would like to thank all of the patients, families, health care providers, and our own team members for bringing this goal to fruition.”

Eflapegrastim is a novel, long‐acting recombinant human granulocyte-colony stimulating factor (G‐CSF) that consists of a recombinant human G‐CSF analog conjugated to a human IgG4 Fc fragment via a short polyethylene glycol linker.²

The ADVANCE and RECOVER trials both evaluated the efficacy and safety of eflapegrastim vs pegfilgrastim in the management of neutropenia in patients with breast cancer receiving docetaxel and cyclophosphamide.

ADVANCE and RECOVER enrolled patients with early-stage breast cancer who were randomly assigned to fixed‐dose eflapegrastim at 13.2 mg/0.6 mL(3.6 mg G‐CSF) or standard pegfilgrastim (6 mg G‐CSF) following standard docetaxel plus cyclophosphamide chemotherapy for 4 cycles.^3,4 Subcutaneous injections of eflapegrastim or pegfilgrastim were administered on day 2 of each cycle, approximately 24 hours after chemotherapy. Patients received 75 mg/m² of intravenous (IV) docetaxel and 600 mg/m² of IV cyclophosphamide on day 1 of every 21-day cycle.

The primary end point in each trial was the duration of severe neutropenia in cycle 1 of treatment. Secondary end points included duration of severe neutropenia in cycles 2 to 4, time to absolute neutrophil count (ANC) recovery, depth of ANC nadir, incidence of febrile neutropenia, incidence of neutropenic complications, relative dose intensity, and safety.

Data from ADVANCE showed that patients in the eflapegrastim group (n = 196) had incidence of severe neutropenia in cycle 1 of 15.8%, compared with 24.3% for the pegfilgrastim arm (n = 210), resulting in an 8.5% absolute and a 34.9% relative risk reduction (P = .034).²

The mean cycle 1 duration of severe neutropenia in the eflapegrastim arm was 0.20 ± 0.503 days vs 0.35 ± 0.683 days for the pegfilgrastim arm, resulting in a difference in mean duration of severe neutropenia of −0.148 days (95% CI, −0.264 to −0.032). This met the study's primary endpoint of non-inferiority (P < .0001).

In RECOVER, patients in the eflapegrastim arm (n = 118) experienced a mean cycle 1 duration of severe neutropenia of 0.31 ± 0.688 days, compared with 0.39 ± 0.949 days in the pegfilgrastim arm (n = 119) for a difference in mean duration of severe neutropenia of −0.073 days (95% CI, −0.292 to −0.129).⁵ The incidence of severe neutropenia in cycle 1 of 20.3% in the eflapegrastim arm compared with 23.5% in the pegfilgrastim arm.

Regarding safety, data from ADVANCE and RECOVER showed that the most common adverse effects (AEs) occurring in more than 20% of patients were fatigue, nausea, diarrhea, bone pain, headache, pyrexia, anemia, rash, myalgia, arthralgia, and back pain. Four percent of patients who received eflapegrastim discontinued treatment due to AEs, and 3 patients discontinued due to rash.

References

1. Spectrum Pharmaceuticals receives FDA approval for Rolvedon™ (eflapegrastim-xnst) injection. News release. Spectrum Pharmaceuticals. September 9, 2022. Accessed September 9, 2022. https://bwnews.pr/3DayQAD
2. Schwartzberg LS, Bhat G, Peruero J, et al. Eflapegrastim, a long‐acting granulocyte‐colony stimulating factor for the management of chemotherapy‐induced neutropenia: results of a phase III trial. Oncologist. 2020;25(8):e1233-e1241. doi:10.1634/theoncologist.2020-0105
3. SPI-2012 vs pegfilgrastim in the management of neutropenia in participants with breast cancer with docetaxel and cyclophosphamide (ADVANCE). ClinicalTrials.gov. Updated March 2, 2022. Accessed September 9, 2022. https://clinicaltrials.gov/ct2/show/NCT02643420
4. SPI-2012 vs pegfilgrastim in management of neutropenia in breast cancer participants with docetaxel and cyclophosphamide. ClinicalTrials.gov. Updated March 2, 2022. https://clinicaltrials.gov/ct2/show/NCT02953340
5. Rolvedon. Prescribing information. Spectrum Pharmaceuticals; 2022. Accessed September 9, 2022. https://bit.ly/3KZLmFb