The first bispecific antibody therapy for multiple myeloma (MM)! Johnson & Johnson Tecvayli (BCMAxCD3) Approved by the US FDA!

October 26, 2022 /BioValleyBIOON/ --Janssen Pharmaceuticals, a division of Johnson & Johnson (JNJ), today announced that the U.
S.
Food and Drug Administration (FDA) has approved ready-to-use T cell redirected BCMAxCD3 bispecific antibody Tecvayli (teclistamab-cqyv) for the treatment of relapsed or refractory (R/S.
R) Multiple myeloma (MM) adult patients
.

Tecvayli was approved
through an accelerated approval process.
Continued approval of this indication will depend on the validation and description
of clinical efficacy in confirmatory trials.

Notably, Tecvayli is the first bispecific antibody therapy (BCMAxCD3)
approved for the treatment of multiple myeloma (MM).
Tecvayli is an off-the-shelf product that is administered
by subcutaneous injection.
In the U.
S.
and EU, Tecvayli was granted breakthrough therapy designation (BTD) and Priority Drug Designation (PRIME),
respectively.

Tecvayli is a first-in-class BCMAxCD3 bispecific T cell-binding antibody that targets CD3 receptors expressed on the surface of T cells as well as B cell maturation antigen (BCMA) expressed on the surface of multiple myeloma (MM)
cells and some healthy B lines.
CD3 is involved in the activation of T cells, and the expression level of BCMA on MM cells is significantly increased
.
Tecvayli redirects CD3-positive T cells to MM cells expressing BCMA to induce cytotoxicity
against target cells.

Teclistamab mechanism of action

In vitro, teclistamab is able to activate T cells, triggering the release of various proinflammatory cytokines, leading to multiple myeloma (MM) cell lysis
.
Preclinical studies have shown that teclistamab kills myeloma cell lines and myeloid of myeloid
origin from patients who have previously received multiple regimens (over-pretreatment) R/R MM.

Tecvayli represents Janssen's regulatory-approved 4th multiple myeloma therapy and will further enrich its industry-leading oncology portfolio
.
The approval of Tecvayli will provide an important new treatment option
for R/R MM patients with limited treatment options.

Tecvayli is produced and developed under a license agreement
between Janssen Biotech and Genmab for the use of the DuoBody® technology platform.
Currently, Tecvayli is being evaluated
in several monotherapy and combination therapy clinical studies.

MajesTEC-1 study results (Image source: Tecvayli US Prescription Information)

The approval is based on the results of the
pivotal Phase 1/2 MajesTEC-1 study (NCT03145181 [Phase 1], NCT04557098 [Phase 2]).
This is an open-label, multicenter clinical trial evaluating the efficacy and safety
of teclistamab in patients with relapsed or refractory multiple myeloma (R/R MM) who have been previously treated with multiple regimens (heavily-pretreated, over-pretreated).

The response population included 110 patients (median age: 66 years [33-82]), with a median prior treatment of 5 lines (range: 2-14), 78 percent who had received at least 4 lines of therapy, and 81 percent who had received stem cell transplantation
.
All patients had previously received three classes of drugs (proteasome inhibitors, immunomodulators, anti-CD38 monoclonal antibodies), and 76% were refractory to class III drugs (proteasome inhibitors, immunomodulators, anti-CD38 monoclonal antibodies).

The efficacy measure is the overall response rate (ORR), which is determined
by an independent review committee (IRC) based on the 2016 criteria of the International Myeloma Working Group (IMWG).

The results showed that the overall response rate (ORR) of Tecvayli treatment was 61.
8% (95% CI: 52.
1%, 70.
9%); In particular, 28.
2% of patients achieved a complete response (CR) or better (CR or a strict complete response [sCR]).

In patients in remission, the median time from treatment to first confirmation of remission was 1.
2 months (range 0.
2 to 5.
5 months).

The median follow-up was 7.
4 months, and the median duration of response (DOR) had not yet been achieved, with an estimated DOR rate of 90.
6% (95% CI: 80.
4%, 95.
7%) at 6 months and an estimated 9-month DOR rate of 66.
5% (95% CI: 38.
8%, 83.
9%)
.

In the safe population of the MajesTEC-1 study (n = 165), the most common adverse reactions (>20%) were fever, cytokine release syndrome (CRS), musculoskeletal pain, injection site reactions, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea
.
The most common grade 3 to 4 laboratory abnormalities (>20%) are lymphopenia, neutropenia, leukopenia, decreased hemoglobin, and thrombocytopenia
.
(Bio Valley Bioon.
com)

U.
S.
FDA APPROVES TECVAYLI™ (TECLISTAMAB-CQYV), THE FIRST BISPECIFIC T-CELL ENGAGER ANTIBODY FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA