Evaluation: Similar safety profile of Biosimilar, reference Pegfilgrastim in clinical studies

The authors of the review article comparing the safety profile of the biologic drug pegfilgrastim and products originating from the EU and the United States concluded: Pegfilgrastim biosimilars are currently approved or applied for approval. Review in the United States demonstrated a high degree of similarity and comparability with the reference product with no unexpected safety findings. reference products.

This review includes 12 phase 1 studies and 4 phase 3 clinical trials comparing the pegfilgrastim biosimilar to the reference product. In these 16 trials, 2978 participants received the biosimilar and 3787 received the reference product. Biosimilars studied in the studies included pegfilgrastim-bmez (Ziextenzo), pegfilgrastim-fpgk (Stimufend), pegfilgrastim-apgf (Nyvepria), pegfilgrastim-jmdb (Fulphila), and pegfilgrastim-cbqv (Udenyca).

Filgrastim and pegfilgrastim are recombinant human granulocyte colony-stimulating factor (G-CSF) analogues; Pegfilgrastim (product reference: Neulasta) is a longer-acting form of filgrastim. Filgrastim and pegfilgrastim bind to G-CSF receptors, initiating signaling pathways that lead to proliferation, differentiation, and survival of hematopoietic cells. These G-CSF biologics are used to prevent febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy.

Side effects in phase 1 studies

In phase 1 studies, reviewers found that the majority of treatment emergent adverse events (TEAEs) were mild or moderate in severity and that the incidence of TEAEs was similar between biosimilars. sequence and reference products. According to the report, drug-related grade 3 or higher TEAE studies ranged from 0%-10% and 0%-9% of participants receiving the biosimilar and the reference product. Serious adverse event (SAE) rates were low and similar between the biosimilar (0%-1.4%) and the reference product (0%-1.6%). TEAEs leading to study discontinuation, reported in 6 of 12 trials, occurred in 2.9% of subjects receiving the biosimilar and 3% of subjects receiving the reference product.

In phase 1 studies, headache rates ranged from 6%-68% in the biosimilar group and 9%-71% in the reference product group. Bone pain occurred in 16%-78% of participants receiving the biosimilar and 18%-75% of participants receiving the reference product. According to the authors, the incidence of other musculoskeletal and connective tissue disorders was similar between groups, as were injection site pain and bruising. Changes in white blood cell counts were also common TEAEs in the phase 1 study, the authors said.

Side effects in phase 3 studies

In 4 phase 3 trials in breast cancer patients receiving TAC chemotherapy (docetaxel, doxorubicin, cyclophosphamide), drug-related study TEAEs occurred in 12%-34% of patients receiving biosimilars and 14.6%-28.1% of patients used the reference product. . Discontinuation rates due to TEAEs were low for both biosimilars (1.3%-3.2%) and reference products (0%-3.3%). SAEs occurred in 1.5%-18.7% of patients treated with biosimilars and in 13%-21% of patients treated with the reference product. Twelve deaths were reported, none considered related to pegfilgrastim treatment.

Headache rates in phase 3 trials ranged from 9%-20% in the biosimilar group and 12%-28% in the reference product group. Bone pain occurred in 40%-45% of patients treated with the pegfilgrastim biosimilar and in 36%-56% of patients treated with the reference product. As with the phase 1 studies, the authors said the incidence of other musculoskeletal and connective tissue disorders was similar between groups and that changes in white blood cell counts were common TEAEs . The incidence of febrile neutropenia ranged from 5%-10% in patients treated with biosimilars and 2%-13% in patients treated with reference products.

Regarding adverse events of particular concern, the authors said they were rarely reported and there were no notable differences between biosimilars and biologics. [reference products]. They noted that the large variation in AE incidence they observed was due to a high degree of clinical and methodological heterogeneity across trials.

Immunogenicity

In phase 1 trials, anti-drug antibody (ADA) rates ranged from 6%-29% in the biosimilar group and 7%-33% in the reference product group; The rate of neutralizing antibodies ranged from 0.2%-1.4% and 0.2%-0.5%. In phase 3 trials, the authors reported that the incidence of ADA was also low and had similar incidence rates, ranging from 1%-4.4% for biosimilars and 1%-8 .3% for reference product. No phase 3 studies reported neutralizing antibodies.

The authors concluded that the safety profile of biosimilar pegfilgrastim was similar to the reference products in the phase 1 and phase 3 studies and consistent with the known safety profile of pegfilgrastim. They added that their conclusions were consistent with a 2019 meta-analysis, which found no significant differences in efficacy or safety between the biosimilar pegfilgrastim and reference products.

Authority to solve

Loaiza-Bonilla A, Trang RD. Achieving leukemia equity: are the safety profiles of biosimilar and reference pegfilgrastim comparable? Future Oncol. 2023. doi:10.2217/fon-2023-0026