Innovent and IASO Bio Present Updated Data of BCMA CAR-T Cell Therapy (Equecabtagene Autoleucel) at EHA 2022
Innovent Biologics, Inc. a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, and IASO Biotherapeutics a clinical-stage biopharmaceutical company engaged in discovering, developing, and manufacturing innovative cell therapies and antibody products, today jointly announced that the updated data from phase 1/2 study of Equecabtagene Autoleucel (Innovent R&D code: IBI326, IASO Bio R&D code: CT103A), a fully-human anti-B cell maturation antigen chimeric antigen receptor T-cell therapy for the treatment of relapsed and/or refractory multiple myeloma (R/R MM), was presented in the form of an oral presentation at the 27th European Hematology Association Annual Meeting in Vienna on June 9-12, 2022.
The updated data from the Phase 1/2 study with a longer duration of follow-up in more patients has showed durable and deepening efficacy, manageable safety and long-term in vivo persistence, indicating that Equecabtagene Autoleucel has the potential to be a breakthrough therapy for patients with R/R MM.
The updated data is from the 14 clinical sites involved in the Phase 1/2 clinical study of Equecabtagene Autoleucel (ChiCTR1800018137, NCT05066646) in the treatment of patients with R/R MM. As of the data cutoff date of January 21, 2022, 79 patients received recommended phase 2 dose of 1.0×106 CAR-T cells/kg with the median follow-up of nine months (range 1.2, 19.6) and median prior five lines of therapy (range 3,23). Among the 79 patients, 34.2% (27/79) had high-risk cytogenetic abnormalities, 34.2%（27/79）had extramedullary multiple myeloma (EMM), and 15.2%（12/79）had received prior CAR-T therapy.
Equecabtagene Autoleucel demonstrated a favorable and manageable safety profile: Among the 79 patients, 94.9% (75/79) experienced cytokine release syndrome (CRS). The majority experienced 1~2 CRS, and no patient experienced grade 3 CRS. The median time to CRS onset was six days after infusion, and the median duration of CRS was five days. Only two patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS), including one patient who experienced grade 1 ICANS and one who experienced grade 2 ICANS. All patients with CRS or ICANS have recovered.
Equecabtagene Autoleucel showed favorable and durable efficacy: Among the 79 patients, the overall response rate (ORR) was 94.9% (75/79), with "89.9% (71/79)" of those patients achieving very good partial response (VGPR) or deeper responses, and the complete response/stringent complete response (CR/sCR) rate was 68.4% (54/79). Equecabtagene Autoleucel also demonstrated favorable efficacy in 10 patients with EMM, achieving an ORR of 100% (10/10) and a CR/sCR rate of 90.0% (9/10). In all 79 patients, 92.4% (73/79) achieved minimal residual disease (MRD) negativity, all CR/sCR subjects achieved MRD negativity, and the median duration of MRD negativity was not reached.
Equecabtagene Autoleucel demonstrated favorable efficacy in patients who had received prior CAR-T therapy: Among the 12 patients who previously received CAR-T therapy, the ORR was 75.0% (9/12), with 41.7% (5/12) of those patients achieving CR/sCR.
Equecabtagene Autoleucel demonstrated robust expansion and prolonged persistence: The expansion of Equecabtagene Autoleucel in peripheral blood reached the peak at a median of 12 days, with a median Cmax of 92,000 copies/ug DNA. Equecabtagene Autoleucel was still detectable in 62.3% (38/61) and 53.3% (8/15) of the subjects who completed 6-months and 12-month follow-ups after infusion. Soluble BCMA in peripheral blood of patients rapidly declined after Equecabtagene Autoleucel infusion and persistently remained below the detectable limit.
Equecabtagene Autoleucel has low immunogenicity: 16.5% (13/79) of the subjects tested anti-drug antibody (ADA)-positive after Equecabtagene Autoleucel infusion. Among them，1.3% (1/79) tested ADA-positive before Equecabtagene Autoleucel infusion, and 2.5% (2/79) tested ADA-positive within three months.
Prof. Chunrui Li, MD, PhD, from Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, stated "Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. In our previous studies, Equecabtagene Autoleucel has shown excellent efficacy and manageable safety profiles. Its CAR structure contains fully human single-chain fragment variables (scFvs) to bypass potential anti-CAR immunogenicity of the host while retaining antitumor activity. At the 27th EHA conference, we updated the data on the efficacy and safety of Equecabtagene Autoleucel in R/R MM patients with longer median follow-up extended to 9.0 months, the CR/sCR deepened to 68.4%, compared with the CR/sCR of 58.2% with a median follow-up of 7.0 months, which were released at 63rd ASH conference in 2021. The updated data showed long-lasting safety and deepening efficacy of Equecabtagene Autoleucel. We are glad that Equecabtagene Autoleucel also shows favorable efficacy on patients who have relapsed after receiving prior CAR-T therapy. This has meaningful clinical value and is worthy of further exploration in the clinic to potentially bring forth new hope to patients with R/R MM."
About Multiple Myeloma (MM)
Multiple Myeloma is a deadly blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems, and bone fractures. For multiple myeloma patients, common first-line drug treatments include proteasome inhibitors, immunomodulatory drugs, and alkylating agents. While treatment may result in remission, most patients will inevitably enter the relapsed or refractory stage as there's currently no cure. As a result, there is a significant unmet need for patients with relapsed/refractory multiple myeloma. In the United States, MM accounts for nearly 2% of all cancer cases, and more than 2% of cancer-related deaths.
According to Frost & Sullivan, the number of new MM cases in the United States rose from 30,300 in 2016 to 32,300 in 2020 and is expected to increase to 37,800 by 2025. Additionally, the total number of patients diagnosed with MM increased from 132,200 in 2016 to 144,900 in 2020 and is expected to rise to 162,300 by 2025. In China, the number of new MM cases rose from 18,900 in 2016 to 21,100 in 2020 and is expected to increase to 24,500 by 2025. The total number of patients diagnosed with MM in China increased from 69,800 in 2016 to 113,800 in 2020 and is expected to rise to 182,200 by 2025.
About Equecabtagene Autoleucel
Equecabtagene Autoleucel is an innovative therapy co-developed by Innovent and IASO Bio, with a fully-human anti- BCMA CAR-T cell therapy which uses lentivirus as a gene vector to transfect autologous T cells. The CAR contains a fully-human scFv, CD8a hinge and transmembrane, and 4-1BB-mediated co-stimulation and CD3ζ activation domains. Based on rigorous screening and comprehensive in vivo and in vitro evaluation, Equecabtagene Autoleucel is proven to have potent and rapid anti-myeloma activity and outstanding safety, efficacy, and persistence results.