# FDA Approvals of Biologics in 2022
## 4 Therapeutic Indications and Mechanisms of Action  
### Cancer  
Of the 15 Biologics approved in 2022, six were indicated for the treatment of a diversity of cancers (Table 3). Comparatively, we had four Biologics approved indicated for cancer approved in 2019, eight in 2020, and six in 2021 [1]. From 2019, there has clearly been a growth aimed at cancer in the Biologics market. The first-in-class Biologic, namely the bispecific fusion protein KimmtrakTM (tebenta-fusp), which is intravenously administered, is the first drug to date specifically for the treatment of metastatic uveal melanoma in HLA-A-positive patients, leading the immune system directly to the cancer cell [19]. One arm of tebentafusp (anti-CD3 effector) binds to T lymphocytes, later dragging the T cell to the cancer cell. This immune cell must bind to glycoprotein 100 (gp100), which may be inside the tumor cell, and therefore needs to \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Year** & **Biologics Approved** &
\begin{tabular}{c} **Original Drug Status Granted** \\ **for New Biologics** \\ \end{tabular} & **References** \\ \hline
2019 & 12 & 9 (75\%) & [6] \\
2020 & 15 & 10 (66\%) & [5] \\
2021 & 14 & 7 (50\%) & [4] \\
2022 & 15 & 7 (46\%) & [3] \\ \hline \hline \end{tabular}
\end{table} 
Table 2: _Cont._ \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Trade Name and** & **Class** & \begin{tabular}{c} **Target/Mechanism** \\ **of Action** \\ \end{tabular} & \
\begin{tabular}{c} **Original** \\ **Approval Date** \\ \end{tabular} & **Manufacturer** &
\begin{tabular}{c} **Therapeutic** \\ **Indication** \\ \end{tabular} \\ \hline KimmtrakTM (tebentafusp) 1 [FOOTNOTE:1]Footnote 1: Orphan Drug: TCR—T-Cell Receptor; gp100—Glycoprotein 100; CD—Cluster of Differentiation; LAG-3—Lymphocyte Activation Gene-3; PD—T-Programmed Death Receptor-1; CTLA—T-V Cytotoxic T-lymphocytes: Associated Antigen 4; uHCC——Unresectableable Hepatocellular Cardiac Carcinoma; NSCLC—T-NumoS Cell Lung Cancer; BCM—B-Cell Maturation Antigen; ADC—Antibody-Drug Conjugate; IgG1—Immunoglobulin G 1; DM4—Antitubulin Agent; FR—Folate Receptor \(\alpha\); PROC—Platinum-Resistant Epithelial Ovarian Cancer; and PPC—Primary Peritoneal Cancer. & & \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Biologics for cancer approved by the Food and Drug Administration in 2022.  
be presented to the tumor cell surface through the human leukocyte antigen (HLA). The other arm of tebentafusp (T-cell receptor arm) then targets gp100, binding to the melanoma cell and activating the T cell, which then kills the melanoma cell. Other Biologics have previously been approved for the treatment unresectable or metastatic melanomas, namely Yervoy(tm) (ipilimumab) in 2011, Keytruada(tm) (pembrolizumab) and Opduulag(tm) (nivolumab) in 2014 [28], Tecentria(tm) (atezolizumab) in 2016 [1], and Opdualag(tm) (relatlimab and nivolumab) in 2022. However, tebentafusp is the first Biologic indicated for metastatic uveal melanoma. This type of cancer is very different from other melanomas as it shows distinct patterns, pessimistic prognosis, and a high likelihood of metastasis [29]. These characteristics thus make Kimmtrak(tm) an important breakthrough. Overall Survival (OS) was the main measure found in the literature for Kimmtrak(tm), with a median OS of 21.7 months vs. 16 months for the control group [19; 29]. For Opdualag(tm), which is intravenously administered, the main measure found was Progression-Free Survival (PFS) vs. nivolumab alone, with a PFS of 10.1 months for Opdualag(tm) vs. 4.6 months for nivolumab [21]. As shown in Ref. [30], the combination of mAbs such as Opdualag(tm) (nivolumab and relatlimab), which was approved this year, offers the interesting advantage of simultaneously targeting multiple pathways. Opdualag(tm) provides a first-in-class mechanism of action by carrying two fully human mAbs, the first one targeting LAG-3 receptors and the second one PD-1 receptors, thereby increasing T-cell activation [21]. Bispecific mAbs can also target more than one pathway.