Multiple myeloma (MM) is a hematologic malignancy, and MM accounting for about 1.8% of all cancers and 18% of all hematologic malignancies in the United States. MM is common in older populations aged 65 – 74 years, and the median age of onset is 69 years. In 2020, there were 32,270 new MM cases and 12,830 deaths in America.
Over the past 20 years, the treatment of multiple myeloma has made tremendous progress, including the Johnson & Johnson developed proteasome inhibitor Bortezomib and the CD38 mab Daratumumab, and many drugs have become the core of the standard therapy for MM patients. MM has brought huge revenue to Johnson & Johnson, with Daratumumab alone breaking $6.1 billion in revenue in 2021.
Due to the high degree of malignancy of MM disease, either a proteasome inhibitor (PI), an immuno-suppressive agent (IMiD), or an anti-CD38 mAb could not alter the outcome of MM relapse. The emergence of Carvykti (West olense) changed the treatment pattern of relapsed refractory MM with the adverse data of ORR 97% and sCR 67%. The curative effect is incredible, and the revenue brought by it is also considerable. As of September 30 of this year, according to Legendary Biology and Janssen Biotech, Inc.(Janssen) Cooperation and licensing agreement entered into on December 21,2017, and Carvykti generated net trade sales of approximately $55 million.
How well does the Teclistamab work out?
Teclistamab remains effective in patients undergoing multiline therapy. In the phase MajesTEC-1I-study, 165 patients of rrMM (including PI, IMiD and anti-CD38 antibodies) were treated at 1.5mg / kg once weekly after receiving increasing doses of 0.06mg / kg and 0.3mg / k g. The primary endpoint was the overall remission rate. The median follow-up time was 14.1 months, the overall remission rate was 63.0%, the median remission duration was 18.4 months, and the median progression-free survival was 11.3 months.
In terms of efficacy alone, Carvykti is slightly better. However, Teclistamab is more safe compared to CAR-T. The CARTITUDE-1 study showed that cytokine release syndrome occurred in 95% of the patients receiving Carvykti (4% grade 3 to 4%), immune effector cell-associated neurotoxicity syndrome was 21% (4% grade 3 to 4%), and six patients died of treatment-related adverse effects. The incidence of Teclistamab cytokine release syndrome was 72.1% (including 0.6%, grade 3; not grade 4), immune effector cell-related neurotoxicity syndrome was 3.0% (both grade 1 or 2), and other common adverse effects were neutropenia (70.9%; grade 3 or 4,64.2%), anemia (52.1%; 37.0%), and thrombocytopenia (40.0%; grade 3 or 4,21.2%), and 76.4% (grade 3 or 4,44.8%).
Compared with the CAR-T treatment method that collects patient cells and returns the drugs after treatment, the administration method of Teclistamab subcutaneous injection also brings more convenience to clinical treatment. It's worth noting that Johnson & Johnson priced Teclistamab at $474,000 a year, even higher than $465,000 a year, which is "equal" in terms of treatment accessibility. By comprehensive comparison, there is no significant difference between Teclistamab and Carvykti, and we may see that the different products of Johnson & Johnson are competing products.
How is Teclistamab located in the clinical treatment?
There is no doubt that Teclistamab is currently used after PI, IMiD and anti-CD38 antibody treatment progress, but as analyzed above, the data of Teclistamab in clinical research are not overwhelming advantage over Carvykti, and whether CAR-T or Teclistamab after progress remains to be preferred on the feedback from real-world research data.
Both Teclistamab and CAR-T can play a role in rrMM treatment. In addition to Carvykti, a number of CAR-T drugs such as Abecma and CT103A can catch up later. Despite the remarkable efficacy of CAR-T on rrMM, some patients develop drug resistance shortly after infusion, with a median PFS of about 8.8 to 18.3 months and a 1-year sustained remission rate of about 70% in patients achieving sCR or CR.With different treatment principles, Teclistamab may play a place in patients who progress after CAR-T treatment, namely, Teclistamab as the posterior treatment of CAR-T treatment progression.
Bortezomib and Daratumumab have taken the first-mover advantage in MM treatment, and the listed Teclistamab is no less prominent in MM dual antibody therapy. In addition to the GPRC5D / CD3 dual antibody still in development, other companies have lost the lead in the market of refractory and relapsed MM. In the era of immunotherapy and cell therapy, domestic innovative drugs are gradually catching up, but Chinese enterprises are still in their initial stage in terms of building patent barriers, multi-target and multi-mechanism pipeline distribution, and the joint layout of upstream and downstream target sites. In the future, with the improvement of the scale of the pharmaceutical industry, the collision between Chinese pharmaceutical enterprises and foreign giants is inevitable, and Johnson & Johnson's layout idea in the field of MM therapy is worth learning.
