FDA Accepts BLA for Pegfilgrastim Biosimilar to Treat Chemotherapy-Induced Infection

A Biologics License Application (BLA) has been accepted by the FDA for MSB11455, a biosimilar for pegfilgrastim (Neulasta), for consideration as treatment of patients with chemotherapy-induced infection associated with febrile neutropenia, Fresenius Kabi developer of the biosimilar, announced in a press release.¹

“Pegfilgrastim plays a vital role in oncology care, and this acceptance by FDA is an important step toward giving oncologists and their patients greater access by providing another option to help support the immune system following chemotherapy,” said Seema Kumbhat, MD, chief medical officer for Fresenius Kabi.

The biosimilarity of MSB11455 to pegfilgrastim was confirmed in 2 studies, of which 1 study evaluated the safety and tolerability of MSB11455 compared with pegfilgrastim (NCT03251339) and the other study (NCT03251248) assessed the pharmacokinetic and pharmacodynamic similarity of MSB11455 and pegfilgrastim.

The safety/tolerability trial was a double-blind, 2-dose, randomized, parallel-group, group-sequential, immunogenicity study in which 404 healthy patients were enrolled and 336 were randomized to receive either the pegfilgrastim biosimilar or pegfilgrastim itself. Baseline characteristics were balanced between the study 2 groups with the average age being 56.8 years. The population was predominantly male, and 4.8% of participants were anti-PEG antibody-positive.²

Overall, the study showed that the safety and tolerability profiles of the 2 drugs were similar. Treatment-emergent adverse events (TEAEs) occurred in 99.4% of patients who received MSB11455 and 99.4% of patients who received pegfilgrastim. The most common TEAEs in the biosimilar and pegfilgrastim itself arms were musculoskeletal and connective tissue disorders and nervous system disorders such as headache (62.5 % vs. 71.4%), bone pain (67.3% vs.60.1%), spinal pain (39.9% vs. 40.5%), and upper respiratory infection (19% vs. 11.9%), respectively. Treatment discontinuations caused by TEAEs were the same in both groups. Serious AEs were rare in both arms. No deaths occurred.

In the phase I PK/PD study, the comparability of the 2 agents was demonstrated in 244 patients. Ninety percent of confidence intervals of MSB11455 compared with pegfilgrastim met the pre-defined range for equivalence, which was (80.00%–125.00%): AUC0–∞ (96.59, 112.82), AUC0–last (97.29, 113.96), Cmax (97.13, 114.99), Emax (98.74, 102.39) and AUE0–t (97.30, 100.23). Additionally, the study investigators did not detect any filgrastim-specific neutralizing antibodies in either treatment sequence.³

The eligibility criteria for both clinical trials were alike. Participants in the safety/tolerability trial were required to be in good health, which was defined by their medical history, physical examination, vital signs, and clinical laboratory test. The PK/PD study also had set criteria for eligibility. In terms of exclusions, patients could not have hypersensitivity to any component of MSB11455 or pegfilgrastim.

Like pegfilgrastim, MSB11455 stimulates white blood cell production in the body to combat infection. If approved by the FDA, MSB11455 will be the first biosimilar for Fresenius Kabb in the United States.¹

_References:

_{FDA accepts for review fresenius kabi’s BLAsubmission for pegfilgrastim biosimilar [news release]. Lake Zurich, Illinois: Fresenius Kabi; May 27, 2020. https://bwnews.pr/2X4IUWA. Accessed May 27, 2020.}

_{Wynne C, Schwabe C, Vincent E, et al. Immunogenicity safety of a proposed pegfilgrastim biosimilar MSB11455 versus the reference pegfilgrastim Neulasta in healthy subjects: A randomized, double-blind trial. Pharmacol Res Perspect. 2020;00:e00578. doi: 10.1002/prp2.578.}

_{Lickliter JD, Griffin P, Vincent E, et al. Pharmacokinetic/pharmacodynamic assessment of a proposed biosimilar MSB11455 versus the currently licensed pegfilgrastim: A randomized, double-blind trial. J Clin Oncol. 2019; 37: (suppl; abstr e14514). doi: 10.1200/JCO.2019.37.15_suppl.e14514.}