# FDA Approvals of Biologics in 2022
## 4 Therapeutic Indications and Mechanisms of Action
### Cancer
However, three distinct mAbs can be combined, as is the case of Pheso(tm), in which all the mAbs target the glycoprotein (GP) of _Zaire ebalovirus_ but in distinct ways. In this regard, between 2015 and 2022, only three combinations of mAbs have received approval, namely the aforementioned Pheso(tm) (pertuzumab, trastuzumab, and hyaluronidase) for Ebola virus, Inmaze(tm) (atoltivimab, maftivimab, odesivimab) to treat early or metastatic breast cancer, both approved in 2020 [1], and Opdualag(tm), which received authorization this year [21]. Of note, the last fusion protein approved by the FDA was in 2018, with tagravofusp, indicated for the treatment of plastic plasmocytoid dendritic cell neoplasm [1]. While the two cancer drugs tagravofusp and tebentafusp received Orphan Drug Status, tebentafusp is the first bispecific fusion protein to get the green light to date. Lunsumio(tm) (mosuentuzumab), a humanized bispecific mAb, has received accelerated approval from the FDA this year. Indicated to treat a type of non-Hodgkin's lymphoma (relapsed or refractory follicular lymphoma (FL), it presented an Objective Response Rate (ORR) of 80% in clinical trials, with 60% of patients presenting a Complete Response (CR) [27]. Patients affected by follicular lymphoma (FL) have very few treatment options when it comes to Biologics. The other treatment option for this condition is rituximab, which was approved in 1997 and was the first mAb for cancer patients. Its therapeutic indications include FL. In comparison with the new bispecific mosuentuzumab, rituximab has an ORR of around 50% and a CR of 6% [31]. In 2017, we saw the approval of a reformulated Rituximab Hycela(tm) (rituximab) with the addition of the human enzyme hyaluronase, which is subcutaneously administered [32]. In this regard, no other mAb has been authorized since Rituximab Hycela(tm), which is indicated to FL; it has taken five years for a new mAb for this disease to come onto the market. Importantly, from 2015 to 2022, the FDA authorized only four bispecific antibodies, namely emicizumab (2017), univantamab (2021), faricimab (2022), and mosuentuzumab (2022) [27; 33; 34; 35]. Imjudo(tm) (tremelimumab) was approved for cancer this year, intravenously administered, indicated for unresectable hepatocellular carcinoma (uHCC) [23]. It is a mAb whose mechanism works by blocking CTLA4, thus stopping the interaction of ligands with the cytotoxic T-lymphocyte-associated antigen 4. The previous cancer Biologic indicated for uHCC to get the green light was Tecentria(tm) (atezolizumab)(2016). This Biologic is also a mAb but, in contrast to tremelimumab, it acts by blocking PD-L1 [1]. For uHCC, both drugs are indicated to be used in combination with other mAbs, namely atezolizumab + bevacizumab, and tremelimumab + durvalumab. In clinical trials, tremelimumab combined with durvalumab, a PD-L1 blocker, demonstrated higher OS (16.43 months vs. control group 13.72 months) and also a better ORR (20.1 vs. 5.1, respectively) [36]. In another advancement by Janssen Biotech Inc., TecvayliTM (techistamab), indicated for relapsed or refractory multiple myeloma (MM), was approved in 2022. Importantly, from 2015 to 2021, the FDA authorized five other Biologics for this disease, namely: DarzaleTM (daratumumab) and EmplicitiTM (elotuzumab), both in 2015, and Darzalex FsproTM (daratumumab and hyaluronidase), SarclisaTM (isatuximab), and the ADC BlenrepTM (belantamab mafodotin), all three in 2020 [1]. Of note, all the Biologics for MM hold Orphan Drug Status. Belantamb mafodotin (approved in 2020) binds to the B-cell maturation antigen (BCMA), and therefore, has a similar mechanism of action to that of the novel techistamab. However, the latter is the first bispecific mAb to treat MM. It binds to BCMA and also to CD3 receptors [24]. In clinical trials, techistamab showed a good ORR, with 40% of the patients presenting a CR [37; 38; 39]. Intravenously administered, ElahereTM (mirvetuximab soravtansine) was the antibody-drug conjugate (ADC) of 2022 to be approved (fast-track process) by the FDA [40].