Approximately 35,000 new cases of multiple myeloma are diagnosed annually in the United States with about 12,540 deaths occurring. Symptomatic multiple myeloma accounts for ~85–90% of total cases, while 8–14% cases have asymptomatic or smoldering multiple myeloma. Despite progress in treating refractory or relapsed multiple myeloma (RRMM), the disease remains incurable, emphasizing the ongoing need for innovative therapies.

The area of treating patients who have progressed or been exposed to BCMA-targeting therapies presents a significant treatment challenge and is a relatively new area of investigation.  G protein-coupled receptor, class C, group 5, member D (GPRC5D) has emerged as a promising target in this pursuit. The recently approved bispecific antibody TALVEY (talquetamab), targeting GPRC5D/CD3, achieved notable response rates—approximately 60% to 70% in patients previously treated with BCMA CAR T-cell therapy and around 45% in those who received BCMA/CD3 treatment. This underscores its potential as a transformative therapy in this challenging treatment landscape.

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CT071 is produced using CARsgen's CARcelerateTM platform, which accelerates manufacturing to under 2 days, resulting in CAR T cells that are younger, healthier, and potentially more effective compared to traditional methods. This enhanced manufacturing efficiency not only increases supply capabilities and reduces costs but also speeds up product availability for patients.

The FDA granted Investigational New Drug (IND) clearance to CT071 in December 2023. However, shortly within the same month the FDA has placed a clinical hold on three of the CAR-T cell therapies candidates including, CT053, CT071 and CT041, following an inspection of the Chinese biotech’s manufacturing facility in Durham, North Carolina.

CARsgen presented preliminary data from the first-in-human trial ( NCT05838131) at EHA 2024 congress. Patients had previously received at least >3 prior lines including a proteasome inhibitor (PI) and an immunomodulatory drug (IMID) or 1 prior line of therapy with prior relapse, lack of response or lack of tolerability to a PI and an IMID were enrolled. 

As of February 28, 2024, the median follow-up time was 4.07 months (2.8–7.4). The median vein-to-vein time (from leukapheresis to infusion) was 21.5 days (18-44). 

• The ORR assessed by the investigator was 90% (55.5%–99.7%), and the partial and very good partial response was 20%.

• Two patients had previously received BCMA/CD19 CAR T; both achieved a response (one SCR and one PR). 

• All the nine patients with evaluable MRD achieved MRD negativity (10–6 threshold), including all five patients with SCR/CR at Week 4.

All 10 infused patients experienced Grade 3 or higher hematologic toxicities. Five patients (50%) had CRS, all at Grade 1 (n = 4) or 2 (n = 1). Four patients experienced treatment- related SAE, including pneumonia (n = 1), decreased appetite (n = 1) and thrombocytopenia (n = 2), and all recovered.

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KOL insights

“The continued challenge of treating relapsed or refractory multiple myeloma underscores the critical need for novel therapeutic approaches. CT071, a fully human CAR T-cell therapy targeting GPRC5D and manufactured via the CARcelerateTM platform, presents a promising avenue with its expedited production, potentially offering enhanced efficacy and shorter treatment timelines.” – MD, United States.

Conclusion 

In the crowded market of multiple myeloma and now with several approved and emerging CAR-Ts, GPRC5D CAR-T therapies represent an innovative approach in the treatment of multiple myeloma. Recent clinical trials have shown encouraging results, with GPRC5D CAR-T demonstrating efficacy even in patients who have relapsed after or are refractory to other treatments like BCMA-targeted therapies. This therapy offers hope for improving outcomes in multiple myeloma, particularly in advanced stages where treatment options are limited.

Created using CARsgen's exclusive CARcelerate platform, CT071 produces CAR T cells that are potentially more robust, younger, and in better condition compared to those manufactured conventionally, with a manufacturing timeframe of under 2 days. This platform boosts supply capacity, reduces manufacturing expenses, and accelerates the availability and delivery of the product to patients.

CT071, if and when approved, will enter a competitive market. It will be up against the approved GPRC5D targeting bispecific antibodies like TALVEY and several emerging GPRC5D targeting therapies such as BMS-986393, AZD0305, Forimtamig, OriCAR-01, and others.