On Oct. 25, the FDA approved Johnson & Johnson's BCMA/CD3 dual antibody Teclistamab for marketing in relapsed and refractory multiple myeloma (MM) after multiline therapy under the trade name Tecvayli. With the addition of Bortezomib, Daratumumab, and Carvykti, J&J has completed the comprehensive layout of treatment for first relapsed MM through multi-line treatment of relapsed and refractory MM (rrMM).
Current status of multiple myeloma treatment
Multiple myeloma (MM) is a hematologic malignancy that accounts for approximately 1.8% of all cancers and 18% of all hematologic malignancies in the United States. MM is common in the elderly aged 65-74 years, with a median age of onset of 69 years. In 2020, there were 32,270 new cases and 12,830 deaths of MM in the United States.
Over the past 20 years, tremendous progress has been made in the treatment of multiple myeloma. A number of drugs, including Bortezomib, a proteasome inhibitor developed by Johnson & Johnson, and Daratumumab, a CD38 mab, have become the core of standard treatment for patients with MM. MM has been a huge revenue driver for J&J, with Daratumumab alone generating more than $6.1 billion in revenue in 2021.
Due to the high degree of malignancy of MM, neither proteasome inhibitors (PI), immunosuppressive agents (IMiD) nor anti-CD38 mab can change the outcome of MM recurrence. The newly born Carvykti (Sidarchiolensa) has changed the treatment pattern of relapsed and refractory MM with the impressive ORR of 97% and sCR of 67%. The efficacy is phenomenal, and the revenue is impressive. As of September 30 this year, Carvykti generated net trade sales of approximately $55 million under the collaboration and licensing agreement between Legendary Biotech and Janssen Biotech, Inc.(Janssen) entered into on December 21, 2017.
How effective is Teclistamab?
Teclistamab remains effective in patients treated with multiple lines of therapy. In the MajesTEC-1 phase Ⅰ-Ⅱ study, 165 rrMM patients with multiline therapy (including PI, IMiD, and anti-CD38 antibody) were enrolled on a weekly subcutaneous dose of 1.5mg/kg followed by incremental doses of 0.06mg/kg and 0.3mg/kg. The primary end point was the overall response rate. The median follow-up time was 14.1 months, the overall response rate was 63.0%, the median duration of response was 18.4 months, and the median progression-free survival was 11.3 months.
Carvykti vs Teclistamab: Which is better?
Purely in terms of efficacy, Carvykti is superior. However, Teclistamab is more secure than CAR-T. Results of the CARtify-1 study showed that 95% of patients treated with Carvykti developed cytokine release syndrome (of which 4% were grade 3 to 4); The incidence of immune effector cell-associated neurotoxic syndromes was 21% (of which grade 3 to 4 accounted for 4%), and six patients died from treatment-related adverse effects. The incidence of Teclistamab cytokine release syndrome was 72.1% (grade 3:0.6%; No grade 4 was observed), the incidence of immune effector cell-associated neurotoxic syndrome was 3.0% (all grade 1 or 2), and the other common adverse effect was neutropenia (70.9%; Grade 3 or 4 accounted for 64.2%), anemia (52.1%; 37.0% of them were grade 3 or 4), and thrombocytopenia (40.0%; Grade 3 or 4 accounted for 21.2%) and the incidence of infection was 76.4% (grade 3 or 4 accounted for 44.8%).
The subcutaneous administration of Teclistamab also brings greater convenience to clinical treatment compared with CAR-T therapy, which involves collecting patient cells, processing and reinfusion. It's worth noting that J&J prices Teclistamab at $474,000 a year, even higher than Carvykti at $465,000 a year, making the two "neck and neck" in terms of treatment accessibility. In a comprehensive comparison, Teclistamab and Carvykti are not significantly different. At that time, we may see the pattern of competing products of the same tumor under J&J.
How to locate Teclistamab in clinical treatment?
The current use of Teclistamab after the progress of PI, IMiD and anti-CD38 antibody therapy is unquestionable, but as analyzed above, the data of Teclistamab in clinical studies are not overwhelming compared with Carvykti. Whether CAR-T or Teclistamab will be preferred after progress remains to be determined by real-world data.
Teclistamab and CAR-T can both play a role in the treatment of rrMM. In addition to Carvykti, a number of CAR-T drugs such as Abecma and CT103A are catching up. Although CAR-T therapy has shown significant efficacy in rrMM, some patients develop resistance soon after infusion, with a median PFS of about 8.8 to 18.3 months, and a 1-year sustained response rate of about 70% in patients with sCR or CR. Due to the different treatment principles, Teclistamab may play a role in patients who have progressed after CAR-T therapy, that is, Teclistamab may be used as a later line of treatment for CAR-T therapy progression.
Bortezomib and Daratumumab already have a first-mover advantage in the treatment of MM. Teclistamab is also the first mover in the treatment of MM. Together with GPRC5D/CD3, which is still in development, other companies have lost ground in the refractory and relapsed MM market. In the era of immunotherapy and cell therapy, domestic innovative drugs are gradually catching up, but in the construction of patent barriers, multi-target and multi-mechanism pipeline layout, upstream and downstream joint layout of target sites, Chinese enterprises are still in the initial stage. In the future with the promotion of pharmaceutical industry scale, the collision of Chinese pharmaceutical enterprises and foreign giants is inevitable, Johnson & Johnson in the MM treatment field layout thinking worth learning.
