FDA Grants RMAT Designation to CAR T-Cell Therapy CT053 for Myeloma

Zonghai Li, MD, PhD

The FDA has granted a Regenerative Medicine Advanced Therapy (RMAT) designation to the investigational anti-BCMA CAR T-cell therapy CT053 for the treatment of patients with relapsed/refractory multiple myeloma.¹

The decision was based on results from an ongoing phase I/II trial (NCT03975907) evaluating CT053 in heavily pretreated patients with relapsed/refractory myeloma. Results presented at the 17th International Myeloma Workshop showed that 21 (87.5%) out of 24 patients with relapsed/refractory disease who had received a median of 4.5 prior lines of therapy had an objective response to CT053 treatment; the complete response rate was 79.2% (n = 19), as of June 30, 2019.²

Additionally, there were no grade ≥3 cases of cytokine release syndrome. Updated findings will be presented at the ASH Annual Meeting in December 2019, CARsgen, the developer of the fully human anti-BCMA autologous CAR T-cell therapy, stated in a press release.

“RMAT eligibility is an important regulatory milestone for CARsgen in the continued development and commercialization of CT053 anti-BCMA CAR T-cell therapy,” Zonghai Li, MD, PhD, chief executive officer of CARsgen, said in the press release. “The RMAT designation indicates that CT053 has demonstrated potential to address unmet medical needs for patients with [relapsed/refractory multiple myeloma]. The designation is a remarkable achievement towards expediting the product development and review of our planned biologics license application and will be invaluable to bringing this cutting-edge advance to patients as quickly as possible.”

The CT053 anti-BCMA CAR-T program has also been granted Investigational New Drug (IND) clearance and Orphan Drug designation from the FDA, as well as authorization of its Clinical Trial Application from Health Canada. In March 2019, the Chinese National Medical Products Administration also cleared an IND application for CT053.

“RMAT as well as the PRIority MEdicines eligibility received from the European Medicines Agency empower us to collaborate closely with the US FDA and EMA to rapidly advance the CT053 development program toward global regulatory approvals,” Li added.

RMAT designation is a program designed to expedite drug development and review processes for promising regenerative medicines and advanced therapies, including CAR T-cell therapies, CARSgen stated in the press release.

The company also stated that RMAT status comprises the same benefits of the FDA's Fast Track and Breakthrough Therapy designations, which provides intensive FDA guidance on efficient drug development, including the ability for early interactions with FDA senior management to discuss surrogate or intermediate endpoints, potential methods to support accelerated approval and satisfy postapproval requirements, potential priority review of the biologics license application, and other opportunities to expedite development and review.

In the open-label, dose-escalation study of CT053, investigators are evaluating the safety and tolerability of the treatment and determining the maximum-tolerated dose and recommended phase II dose. Patients with relapsed/refractory multiple myeloma are enrolled on 1 of 4 cohorts of varying doses.

To be eligible for enrollment, patients had to be ≥18 years old; had received ≥3 prior regimens for myeloma, including ≥1 proteasome inhibitor and 1 immunomodulatory agent; should have relapsed to their last therapy within 12 months or were refractory to their last line of therapy within 60 days; have measurable disease; have an estimated life expectancy >12 weeks; have an ECOG performance status of 0 or 1; and have adequate organ function. Those who previously received CAR T-cell therapy, anti-BCMA therapy, or either allogeneic or autologous stem cell transplantation could not be enrolled.

The primary endpoints are safety and tolerability, as well as dose-limiting toxicity in the phase I portion, and overall response rate (ORR) in the phase II portion of the trial. Secondary endpoints include 12-week ORR, pharmacokinetics, and safety and tolerability at various timepoints.

RMAT designation is a program designed to expedite drug development and review processes for promising regenerative medicines and advanced therapies, including CAR T-cell therapies, CARSgen stated in the press release.

The company also stated that RMAT status comprises the same benefits of the FDA's Fast Track and Breakthrough Therapy designations, which provides intensive FDA guidance on efficient drug development, including the ability for early interactions with FDA senior management to discuss surrogate or intermediate endpoints, potential methods to support accelerated approval and satisfy postapproval requirements, potential priority review of the biologics license application, and other opportunities to expedite development and review.

References

1. CARsgen Announces Investigational CAR-T Therapy CT053 Granted RMAT Designation by the U.S. FDA for R/R Multiple Myeloma. Carsgen Therapeutics. Published October 28, 2019. https://bit.ly/2PwNmtE. Accessed October 31, 2019.
2. CARsgen Announces Investigational CAR-T Therapy CT053 Granted PRIME Eligibility by the European Medicines Agency. Carsgen Therapeutics. Published September 23, 2019. https://prn.to/321jNDo. Accessed October 31, 2019.