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The world's first! Johnson & Johnson BCMA/CD3 bispecific antibody was approved for listing, can "King Fried CP" conquer the 100 billion market?

 Last Update: 2022-10-31
 Source: Internet
 Author: User

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Johnson & Johnson's Janssen announced that its world's first BCMA/CD3 bispecific antibody teclistamab has been approved by the FDA for the treatment of relapsed or refractory multiple myeloma
.

Up to now, there are 7 bispecific antibody drugs on the
market worldwide.

TecListamab has been approved for marketing by the EU on August 24, and the domestic Phase III clinical study of TecListamab began
in October last year.

Table 1 Bispecific antibody drugs marketed worldwide

Source: Online public news collation

At present, as the approval process of bispecific antibody drugs continues to accelerate, the global bispecific antibody market size will rise rapidly, and the global bispecific antibody market size is expected to reach 80.
7 billion US dollars in 2030, with an average compound growth rate of 39.
6% from 2022 to 2030!

Johnson & Johnson BCMA/CD3 bispecific antibody was approved for marketing, and the bispecific antibody drug added another member, can "King Fried CP" capture the 100 billion market?

ORR of 63%

Teclistamab, trade name TECVAYLI®, is a fully humanized bispecific antibody that targets both BCMA and CD3 receptors on the surface of T cells, recruiting CD3-positive T cells near BCMA-expressing myeloma cells, thereby stimulating T cells to kill tumor cells
.

CD3-positive T cells can be recruited near BCMA-expressing myeloma cells, thereby stimulating T cells to kill tumor cells
.

Teclistamab was first granted PRIME (Priority Medicine) designation by the European Medicines Agency (EMA), and was granted breakthrough therapy designation (BDT) by the FDA on June 1, and two months later teclistamab injection was included in the NMPA breakthrough therapy variety for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 3 lines of prior therapy.
At the same time, it has been included in the breakthrough therapy varieties in China and the United States, which shows that its effect in the treatment of multiple myeloma is very significant
.

Teclistamab's approval is based on the positive results of the MajesTEC-1 study, an open-label, multicenter, phase I/II clinical trial (registration numbers: NCT03145181, NCT04557098) to evaluate the efficacy and safety
of Teclistamab in patients with relapsed or refractory multiple myeloma.

To assess the efficacy and safety
of Teclistamab in people with relapsed or refractory multiple myeloma.

The results of the trial, published in the top journal NEJM, included 165 patients with weekly subcutaneous injection of Teclistamab (dose of 1.
5 mg/kg, escalating dose 0.
06 mg/kg, 0.
3 mg/kg).

The results showed that the overall response rate (ORR) reached 63% (104/165), and 58.
8% of patients had a good response of partial response (VGPR) or more, and 39.
4% of patients had a complete response (CR) or more
.

Overall response rate (ORR) of 63% (104/165)

The median duration of response was 18.
4 months, the median progression-free survival was 11.
3 months, and the median overall survival was 18.
3 months
.
The most common adverse event in terms of safety was cytokine release syndrome (CRS) (72%; 0.
6% grade 3, no grade 4), neutropenia (71%; 64% grade 3 or 4) and anemia (55%; 37% Level 3 or 4).

BCMA+CD3, king fried CP?

BCMA is a member of the tumor necrosis factor superfamily protein, mainly expressed in malignant and normal plasma cells and some mature B cells, not expressed in important tissues, and is an effective target for the treatment of multiple myeloma
.

BCMA bispecific antibody drugs have both good efficacy and safety, BCMA target CAR-T drugs in the treatment of blood cancer efficacy is remarkable, a number of drugs ORR of more than 90%, but including serious immune effector cell-associated neurotoxicity syndrome and CRS toxicity problems, ADC drugs although low toxicity but the therapeutic effect and CAR-T and bispecific antibody drugs have a certain gap, BCMA bispecific antibody drugs efficacy and safety between CAR-T and ADC
。

The ORR of multiple drugs exceeds 90%

Figure 1 Schematic diagram of BCMA-targeted immunotherapy constructs Source: Data 3

As early as the 80s of the last century, CD3 targets have entered the development of bispecific antibodies, and the concept of T cell redirection was first proposed in 1985, and after 30 years of research, CD3 targets have gradually matured
.

CD3 molecules are widely distributed in membrane antigens on the surface of mature T cells, and combine with T cell antigen recognition receptors (TCRs) to form complex receptor molecules to activate T cells and realize T cell redirection
.

From the bispecific antibody drugs that have been marketed, it can be seen that Amgen's Blinatumomab, Genentech's Mosunetuzumab and the latest listed teclistamab are all targeting CD3, and the subsequent rapid progress of glofitamab and epcotitama all target CD3, which has become the main target of global bispecific antibody drug development
.

At present, it has become the main target of
global bispecific antibody drug development.

According to the data, a total of 229 listed and under research bispecific antibodies in the world contain CD3 targets, far higher than the second PDL-1, BCMA×CD3 target combination pipeline ranks second with 17, second only to CD3 ×CD20 targets, only domestic CD3 × BCMA combination of bispecific antibodies have 10 models, most of which are in the early clinical stage
.

229 marketed and under development bispecific antibodies contain CD3 targets

Figure 2 Global bispecific antibody target distribution and combination distribution Source: Southwest Securities

Pfizer, Regeneron, AbbVie, Amgen, etc.
have layouts in the field of BCMAxCD3 bispecific antibodies, and domestic Kangnoa Biologics and Shanghai Coast Imai Biologics have made rapid
progress.

Table 2 BCMA/CD3 bispecific antibodies entering the clinical stage

Source: Online public information collation

At present, there are 14 BCMAxCD3 bispecific antibodies in the clinical stage, the vast majority of which are used to treat multiple myeloma
.
The fastest progressing of these is Pfizer Elranatamab (PF-06863135).

Pfizer Elranatamab (PF-06863135).

Elranatamab, a bispecific antibody targeting BCMA and CD3 developed by Pfizer for the treatment of multiple myeloma, has optimized its binding affinity for BCMA and CD3, resulting in stronger
T-cell-mediated anti-myeloma activity.
The purpose of subcutaneous injection is to allow the use of higher doses than intravenous injection without increasing adverse events
.

At the ASCO Annual Meeting in June this year, Pfizer announced the interim analysis data of the Phase 2 MagnetisMM-3 registration trial of elranatamab in patients with relapsed/refractory multiple myeloma, which as of March 23, 2022, analyzed the safety and efficacy of 94 patients receiving elranatamab (patients who received subcutaneous elranatamab 76 mg once a week) as of March 23, 2022, The median follow-up was 3.
71 months, and preliminary efficacy results showed an objective response rate of 60.
6% for elranatamab, with 89.
5% of patients still in progress with no confirmed disease progression or death
.

The objective response rate for elranatamab was 60.
6%, and objective remission was still ongoing in 89.
5% of patients with no confirmed disease progression or death
.

The most common treatment of urgent adverse events were anaemia (43.
6%), neutropenia (38.
3%), thrombocytopenia (28.
7%), lymphopenia (25.
5%), and CRS (60.
6%); In addition, 2.
2% of patients developed immune effector cell-associated neurotoxic syndromes, all grade 2 or less
.

How is Johnson & Johnson laid out?

In the field of multiple myeloma, Johnson & Johnson also has a blockbuster product of daratumumab, with global sales of $6.
023 billion
in 2021.

This year, it was approved for the potential product Carvykti (BCMA CAR-T), which is a CAR-T therapy independently developed by Legend Biologics, a subsidiary of GenScript, in 2017, Legendary Biologics and Janssen reached a license agreement between the two parties to jointly develop and promote Cedarquiolenc, and in February this year, Cedarquiolensis was approved by the US FDA to treat patients with relapsed/refractory multiple myeloma.
Became the first FDA-approved domestic CAR-T cell therapy, which achieved a staggering 98% ORR
in MM patients.

According to GenScript Biologics' announcement, Cedarquiolence's third-quarter sales of approximately $55 million increased 129%
sequentially.

In addition, Johnson & Johnson has a first-in-class CD3 bispecific antibody Talquetamab (GPRC5D x CD3), which has shown very good efficacy
in multiple myeloma.

So far, four bispecific antibody drugs have been approved for marketing this year, in addition to Roche's Glofitamab and AbbVie's Epcoritama have submitted marketing applications, which are expected to be approved in
the near future.

Resources

1.
Johnson & Johnson BCMA/CD3 bispecific antibodies are intended to be included in breakthrough therapy
.

2.
The Agony of Choice—Where to Place the Wave of BCMA-Targeted Therapies in the Multiple Myeloma Treatment Puzzle in 2022 and Beyond.

3.
Pfizer announced positive data
for interim analysis of a Phase 2 MagnetisMM-3 registration trial targeting the BCMA and CD3 bispecific antibody Elranatamab.

4.
Sell 570 million yuan in half a year, where is the future of CAR-T in domestic competition

5.
Southwest Securities and other public information on the Internet

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