# FDA Approvals of Biologics in 2022
## 4 Therapeutic Indications and Mechanisms of Action
### Enzymes and Proteins  
Three out of the fifteen Biologics to get the green light in 2022 fall into the class of proteins and enzymes, as found in Table 7. We discuss the results of the efficacy of these new Biologics compared the ones approved in previous years.  
XenpozymeTM (olipudase alfa) was the first enzyme to be approved by the FDA in 2022. It is a replacement therapy indicated to treat a rare disease named acid sphingomyelinase deficiency (ASMD) (also known as Nieamann-Pick Disease) [91; 92]. The deficiency of acid sphingomyelinase (ASM) leads to the accumulation of sphingomyelin and other lipids, which can cause involvement of the central nervous system (CNS), hepatosplenomegaly, and/or lung impairment. There are two types of ASMD, type A and type B. The former causes hepatosplenomegaly and CNS impairment, while type B leads to hepatosplenomegaly, and liver and lung impairment, and it may not present CNS disruption [95; 96]. In clinical trials, oligupadase alfa demonstrated improved clinical symptoms, including enhanced platelet counts, a reduction in liver and spleen volume, and a greater lung diffusing capacity, and it also cleared sphingomyelin from tissues [97; 98].  
Given the difficulty in managing neutropenia in some cancer treatments, RolvedonTM (eflapegrastim), which has been approved this year, is an important innovation. In this regard, Biologics for chemotherapy-induced neutropenia (CIN) started in 1991 with filgras  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
\begin{tabular}{c} Schar removal \\ with partial- or \\ full-thickness \\ thermal burns \\ \end{tabular} \\ \hline \hline \end{tabular}
\end{table}
Table 7: Proteins and enzymes approved by the Food and Drug Administration in 2022.  
tim, followed by pegfilgrastim in 2002. However, since then, the industry has struggled to develop a new Biologic other than biosimilars for CIN. Effalepgrastim has the addition of an Fc Fragment of a human IgG4 [93], which extends its half-life and increases its absorption by the bone marrow. In clinical trials, efalepgrastim demonstrated non-inferior efficacy in reducing neutropenia compared to pegfilgrastim at a reduced dose of G-CSF (Granulocyte-Colony Stimulating Factor); 3.6 mg and 6.0 mg, respectively, administered in all four cycles. Furthermore, the safety profiles of these two drugs are similar [99; 100; 101].  
In 2022, nexoBridTM (anacaulase) was the only Biologic of topical administration approved with a distinct therapeutic indication: eschar removal in adults with full- or partial-thickness thermal burns. However, it still has significant limitations for the treatment of electrical and chemical burns, or burns to the face and genitalia [94]. Schar removal is a procedure that helps to better manage the wound and wound closure, and when eschar removal occurs in the first hours it can reduce bacterial growth and days of hospitalization [102]. Of note, no Biologic for this indication has been approved by the FDA in recent years.  
Ongoing Clinical Trials for Effalepgrastim  
Spectrum Pharmaceuticals Inc. is testing efalepgrastim for other conditions: pediatric participants with solid tumors or lymphoma and treated with myelosuppressive chemotherapy [103], to compare the effect of efalepgrastim on the duration of neutropenia in patients with early-stage breast cancer [104], but there are still trials to be carried out. No studies were found for anacaulase and dipupadase alfa for diseases other than the primary ones described in the Prescribing Information.