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The year 2022 witnessed the control of the COVID-19 pandemic in most countries through social and hygiene measures and also vaccination campaigns. It also saw a decrease in total approvals by the U.S. Food and Drug Administration (FDA). Nevertheless, there was no fall in the Biologics class, which was boosted through the authorization of 15 novel molecules, thus maintaining the figures achieved in previous years. Indeed, the decrease in approvals was only for the category of small molecules. Monoclonal antibodies (mAbs) continued to be the drug class with the most approvals, and cancer remained the most targeted disease, followed by autoimmune conditions, as in previous years. Interestingly, the FDA gave the green light to a remarkable number of bispecific Biologics (four), the highest number in recent years. Indeed, 2022 was another year without the approval of an antimicrobial Biologic, although important advancements were made in targeting new diseases, which are discussed herein. In this work, we only analyze the Biologics authorized in 2022. Furthermore, we also consider the orphan drugs authorized. We not only apply a quantitative analysis to this year's harvest, but also compare the efficacy of the Biologics with those authorized in previous years. On the basis of their chemical structure, the Biologics addressed fall into the following classes: monoclonal antibodies; antibody-drug conjugates; and proteins/enzymes. [ABSTRACT FROM AUTHOR]

Abstract Eflapegrastim (Rolontis®) is a novel, long‐acting hematopoietic growth factor consisting of a recombinant human granulocyte‐colony stimulating factor (rhG‐CSF) analog conjugated to a human IgG4 Fc fragment via a short polyethylene glycol linker. We report results from a second pivotal, randomized, open‐label, Phase 3 study comparing the efficacy and safety of eflapegrastim to pegfilgrastim for reducing the risk of chemotherapy‐induced neutropenia. Patients with Stage I to IIIA early‐stage breast cancer (ESBC) were randomized 1:1 to fixed‐dose eflapegrastim 13.2 mg (3.6 mg G‐CSF) or pegfilgrastim (6 mg G‐CSF) administered one day after standard docetaxel/cyclophosphamide (TC) therapy for four cycles. The primary objective was to demonstrate noninferiority (NI) of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN; Grade 4) in Cycle 1. A total of 237 eligible patients were randomized 1:1 to receive either eflapegrastim (n = 118) or pegfilgrastim (n = 119). Cycle 1 severe neutropenia was observed in 20.3% (n = 24) of patients receiving eflapegrastim and 23.5% (n = 28) receiving pegfilgrastim. The DSN of eflapegrastim in Cycle 1 was noninferior to pegfilgrastim with a mean difference of −0.074 days (NI P‐value

Eflapegrastim (Rolontis) is a long‐acting granulocyte colony‐stimulating factor (G‐CSF) produced by conjugating a human G‐CSF analogue and a human immunoglobulin G4 Fc fragment, linked via a polyethylene glycol linker. Weight‐based doses of 45 to 270 μg/kg eflapegrastim (12.3‐73.6 μg/kg as G‐CSF) were evaluated in a phase 2 study in patients. Based on these results, a fixed dose of 13.2 mg eflapegrastim (3.6 mg G‐CSF) was compared with pegfilgrastim (6 mg G‐CSF) in 2 phase 3 studies and in a pharmacokinetic single‐arm multicenter study. Absolute neutrophil count (ANC) data from these 3 studies were evaluated in patients with early‐stage breast cancer who were treated with docetaxel and cyclophosphamide (n = 669). Serum concentrations of eflapegrastim were determined by enzyme‐linked immunosorbent assay. Eflapegrastim systemic exposures were higher in cycle 1 than in cycle 3, likely attributable to the higher ANC in cycle 3, increasing neutrophil‐mediated clearance. Eflapegrastim elicited a greater effect on ANC than pegfilgrastim in patients at ∼60% of the G‐CSF dose. Body weight had no clinically significant effect on response, justifying administration of a fixed dose of eflapegrastim. The results from 2 phase 3 studies demonstrate that eflapegrastim at a fixed dose of 13.2 mg (3.6 mg G‐CSF) administered once per chemotherapy cycle is effective in prophylactic treatment of chemotherapy‐induced neutropenia. [ABSTRACT FROM AUTHOR]

Abstract This randomized, open‐label, active‐controlled study investigated the safety and efficacy of three doses of Rolontis (eflapegrastim), a novel, long‐acting myeloid growth factor, versus pegfilgrastim in breast cancer patients being treated with docetaxel and cyclophosphamide (TC). The primary efficacy endpoint was duration of severe neutropenia (DSN) during the first cycle of treatment. Patients who were candidates for adjuvant/neoadjuvant TC chemotherapy were eligible for participation. TC was administered on Day 1, followed by 45, 135, or 270 μg/kg Rolontis or 6 mg pegfilgrastim on Day 2. Complete blood counts were monitored daily when the absolute neutrophil count (ANC) fell to

Eflapegrastim (Rolontis®) is a novel, long‐acting hematopoietic growth factor consisting of a recombinant human granulocyte‐colony stimulating factor (rhG‐CSF) analog conjugated to a human IgG4 Fc fragment via a short polyethylene glycol linker. We report results from a second pivotal, randomized, open‐label, Phase 3 study comparing the efficacy and safety of eflapegrastim to pegfilgrastim for reducing the risk of chemotherapy‐induced neutropenia. Patients with Stage I to IIIA early‐stage breast cancer (ESBC) were randomized 1:1 to fixed‐dose eflapegrastim 13.2 mg (3.6 mg G‐CSF) or pegfilgrastim (6 mg G‐CSF) administered one day after standard docetaxel/cyclophosphamide (TC) therapy for four cycles. The primary objective was to demonstrate noninferiority (NI) of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN; Grade 4) in Cycle 1. A total of 237 eligible patients were randomized 1:1 to receive either eflapegrastim (n = 118) or pegfilgrastim (n = 119). Cycle 1 severe neutropenia was observed in 20.3% (n = 24) of patients receiving eflapegrastim and 23.5% (n = 28) receiving pegfilgrastim. The DSN of eflapegrastim in Cycle 1 was noninferior to pegfilgrastim with a mean difference of −0.074 days (NI P‐value <.0001). Noninferiority was maintained throughout the four treatment cycles (P <.0001 in all cycles). Other efficacy endpoints results were comparable between treatment arms, and adverse events, irrespective of causality and grade, were comparable between treatment arms. The results demonstrate noninferior efficacy and comparable safety for eflapegrastim, at a lower G‐CSF dose, vs pegfilgrastim. The potential for the increased potency of eflapegrastim to deliver improved clinical benefit warrants further clinical study. [ABSTRACT FROM AUTHOR]

Background: Eflapegrastim, a novel, long‐acting recombinant human granulocyte‐colony stimulating factor (rhG‐CSF), consists of a rhG‐CSF analog conjugated to a human IgG4 Fc fragment via a short polyethylene glycol linker. Preclinical and phase I and II pharmacodynamic and pharmacokinetic data showed increased potency for neutrophil counts for eflapegrastim versus pegfilgrastim. This open‐label phase III trial compared the efficacy and safety of eflapegrastim with pegfilgrastim for reducing the risk of chemotherapy‐induced neutropenia. Materials and Methods: Patients with early‐stage breast cancer were randomized 1:1 to fixed‐dose eflapegrastim 13.2 mg (3.6 mg G‐CSF) or standard pegfilgrastim (6 mg G‐CSF) following standard docetaxel plus cyclophosphamide chemotherapy for 4 cycles. The primary objective was to demonstrate the noninferiority of eflapegrastim compared with pegfilgrastim in mean duration of severe neutropenia (DSN; grade 4) in cycle 1. Results: Eligible patients were randomized 1:1 to study arms (eflapegrastim, n = 196; pegfilgrastim, n = 210). The incidence of cycle 1 severe neutropenia was 16% (n = 31) for eflapegrastim versus 24% (n = 51) for pegfilgrastim, reducing the relative risk by 35% (p =.034). The difference in mean cycle 1 DSN (−0.148 day) met the primary endpoint of noninferiority (p <.0001) and also showed statistical superiority for eflapegrastim (p =.013). Noninferiority was maintained for the duration of treatment (all cycles, p <.0001), and secondary efficacy endpoints and safety results were also comparable for study arms. Conclusion: These results demonstrate noninferiority and comparable safety for eflapegrastim at a lower G‐CSF dose versus pegfilgrastim. The potential for increased potency of eflapegrastim to deliver improved clinical benefit warrants further clinical study in patients at higher risk for CIN. Implications for Practice: Chemotherapy‐induced neutropenia (CIN) remains a significant clinical dilemma for oncology patients who are striving to complete their prescribed chemotherapy regimen. In a randomized, phase III trial comparing eflapegrastim to pegfilgrastim in the prevention of CIN, the efficacy of eflapegrastim was noninferior to pegfilgrastim and had comparable safety. Nevertheless, the risk of CIN remains a great concern for patients undergoing chemotherapy, as the condition frequently results in chemotherapy delays, dose reductions, and treatment discontinuations. Myelosuppression, particularly neutropenia, has presented a major challenge in cancer treatment since the introduction of cytotoxic chemotherapy. This article reports the results of a phase III trial that compared the efficacy and safety of eflapegrastim with pegfilgrastim for reducing the risk of chemotherapy‐induced neutropenia. [ABSTRACT FROM AUTHOR]

Abstract: This randomized, open‐label, active‐controlled study investigated the safety and efficacy of three doses of Rolontis (eflapegrastim), a novel, long‐acting myeloid growth factor, versus pegfilgrastim in breast cancer patients being treated with docetaxel and cyclophosphamide (TC). The primary efficacy endpoint was duration of severe neutropenia (DSN) during the first cycle of treatment. Patients who were candidates for adjuvant/neoadjuvant TC chemotherapy were eligible for participation. TC was administered on Day 1, followed by 45, 135, or 270 μg/kg Rolontis or 6 mg pegfilgrastim on Day 2. Complete blood counts were monitored daily when the absolute neutrophil count (ANC) fell to <1.5 × 109/L. Up to four cycles of TC were investigated. The difference in DSN (time from ANC <0.5 × 109/L to ANC recovery ≥2.0 × 109/L) between the Rolontis and pegfilgrastim groups was −0.28 days (confidence interval [CI]: −0.56, −0.06) at 270 μg/kg, 0.14 days (CI: −0.28, 0.64) at 135 μg/kg, and 0.72 days (CI: 0.19, 1.27) at 45 μg/kg. Noninferiority to pegfilgrastim was demonstrated at 135 μg/kg (P = 0.002) and 270 μg/kg (P < .001), with superiority demonstrated at 270 μg/kg (0.03 days; P = 0.023). The most common treatment‐related adverse events (AEs) were bone pain, myalgia, arthralgia, back pain, and elevated white blood cell counts, with similar incidences across groups. All doses of Rolontis were well tolerated, and no new or significant treatment‐related toxicities were observed. In Cycle 1, Rolontis demonstrated noninferiority at the 135 μg/kg dose and statistical superiority in DSN at the 270 μg/kg dose when compared to pegfilgrastim. [ABSTRACT FROM AUTHOR]

• Chemotherapy-induced neutropenia can lead to poor clinical outcomes. • CIN can lead to infections, hospitalizations, mortality, and lower chemotherapy dose intensity. • G-CSF agents have been the standard of care for the prevention of CIN for 30 years. • Emerging therapies will likely change the standard approach for CIN prevention. [ABSTRACT FROM AUTHOR]