Updated BLA Submitted to FDA for Eflapegrastim as Chemotherapy-Induced Neutropenia Treatment

An updated Biologics License Application (BLA) has been submitted to the FDA for eflapegrastim (Rolontis) for the treatment of neutropenia in patients with cancer receiving myelosuppression drugs, according to a press release from Spectrum Pharmaceuticals.¹

Data supporting the updated BLA come from 2 phase III clinical trials, ADVANCE and RECOVER, that investigated the use of eflapegrastim in patients with early-stage breast cancer who developed neutropenia from treatment with myelosuppressive chemotherapy agents.

Spectrum previously submitted a BLA for eflapegrastim in December 2018, which was then voluntarily withdrawn by the company in March 2019.²The new filing addresses requests from the FDA and contains new information on chemistry, manufacturing, and controls for the long-acting granulocyte colony-stimulating factor (G-CSF) agent.¹

“We have submitted a robust package to the FDA that incorporates strong clinical data and addresses previously communicated FDA requests relating to manufacturing processes,” Joe Turgeon, president and CEO of Spectrum, stated in the press release. “Rolontis could be the first novel G-CSF available to healthcare providers in over 15 years.”

In the randomized, active-controlled, open-label, multicenter phase III ADVANCE trial, 406 patients with stage I-IIIA breast cancer were randomized to receive either eflapegrastim or pegfilgrastim. The patients were treated with 4 cycles of adjuvant or neoadjuvant docetaxel and cyclophosphamide chemotherapy and either eflapegrastim 13.2 mg/0.6 mL or pegfilgrastim 6 mg was added on day 2 of each cycle. The primary endpoint of the trial was the noninferiority of eflapegrastim to pegfilgrastim according to the mean duration of severe neutropenia in cycle 1, as assessed by an absolute neutrophil count (ANC) <0.5&times;10⁹/L.³

The mean duration of severe neutropenia was 0.19 days (standard derivation [SD], 0.478) in those treated with eflapegrastim and 0.34 days (SD, 0.668) for pegfilgrastim, achieving noninferiority (95% CI, -0.260 to -0.035;P<.0001). The noninferiority of eflapegrastim was maintained throughout all 4 cycles of treatment.

No significant differences were noted between the treatment arms for the secondary endpoints of time to ANC recovery, depth of ANC nadir, and incidence of febrile neutropenia in cycle 1.

The rates of adverse events (AEs) were similar between the 2 arms, with the most common events being neutropenia, lymphopenia, anemia, and leukopenia.

The RECOVER trial had a similar design to the ADVANCE trial, looking at the noninferiority of eflapegrastim with a primary endpoint of mean duration of severe neutropenia in cycle 1. A total of 237 patients with stage I-IIIA breast cancer were enrolled and treated with adjuvant or neoadjuvant docetaxel and cyclophosphamide with the addition of either eflapegrastim or pegfilgrastim.⁴

The mean duration of severe neutropenia was 0.31 days (SD, 0.688) with eflapegrastim treatment and 0.39 days (SD, 0.949) with pegfilgrastim, which also demonstrated noninferiority (95% CI, -0.292 to 0.129;P<.0001). Noninferiority was maintained across all 4 cycles.

Additionally, the secondary endpoints of time to ANC recovery, depth of ANC nadir, and incidence of febrile neutropenia in cycle 1 did not show significant differences between the 2 treatment arms.

Common grade 3/4 AEs included neutropenia, lymphopenia, anemia, and leukopenia, and the rates were similar in each of the treatment arms. Grade 3/4 bone pain and febrile neutropenia was also observed in less than 5% of patients in each arm.

References

1. Spectrum Pharmaceuticals Announces Submission to the U.S. Food and Drug Administration of Updated Biologics License Application for ROLONTIS