Allogeneic CAR T Recognized for Cutaneous T-Cell Lymphomas

The FDA has granted regenerative medicine advanced therapy (RMAT) designation to CRISPR Therapeutics' allogeneic chimeric antigen receptor (CAR) T-cell therapy for the treatment of CTX130 cutaneous T-cell lymphomas (CTCL), specifically for the treatment of mycosis fungoides and Sézary syndrome (MF/SS).¹

“The RMAT designation is an important milestone for the CTX130 program that recognizes the transformative potential of our cell therapy in patients with T-cell lymphomas based upon encouraging clinical data to date,” Phuong Khanh Morrow, MD, FACP, chief medical officer, CRISPR Therapeutics, said in a statement.¹ "We continue to work with a sense of urgency to bring our broad portfolio of allogeneic cell therapies to patients in need.”

CTX130 is a CD70-targeting gene-edited investigational CAR T therapy being evaluated in 2 ongoing phase 1, multi-center, open-label clinical trials. The COBALT-LYM trial (NCT04502446) is assessing the therapy in relapsed/refractory T or B-cell malignancies and the COBALT-RCC trialis assessing it in relapsed/refractory renal cell carcinoma. Both trials are assessing the safety and efficacy of escalating dose levels, with primary outcomes of adverse event incidence/dose limiting toxicities and overall response rate. Both trials’ secondary outcomes are progression free survival and overall survival. CTX130 has also received orphan drug and regenerative medicine advanced therapy designations from the FDA.

READ MORE: IND Cleared for Non-Hodgkin Lymphoma T-Cell Therapy

CRISPR Therapeutics, along with its collaborator Vertex Pharmaceuticals, also just announced that they will be submitting biologics license applications (BLA) for exagamglogene autotemcel (exa-cel) for rolling review for the treatments of sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT) beginning in November 2022.² Vertex plans to complete the submission by the end of the first quarter of 2023. Vertex is on track to submit by the end of 2022 in the UK and EU.

“We are pleased to have concluded our exa-cel pre-submission meetings with regulators and are excited that FDA has granted a rolling review,” Nia Tatsis, PhD, Executive Vice President and Chief Regulatory and Quality Officer, Vertex, said in a statement.² “We continue to work with urgency to bring forward the first CRISPR therapy for a genetic disease, and one that holds potential to transform the lives of patients with sickle cell disease or beta thalassemia.”

Exa-cel is being investigated in the ongoing phase 1/2/3 open-label CLIMB-111 and CLIMB-121 trials for SCD and TDT, the long-term CLIMB-131 study, and the ongoing, phase 3, open-label CLIMB-141 and CLIMB-151 trials which are currently enrolling participants.

The submission news follows in the footsteps of the FDA’s landmark approval of bluebird bio’s betibeglogene autotemcel (beti-cel) for treating TDT. The therapy, now marketed as ZYNTEGLO, has become the first gene therapy to be approved for blood disorders, with a price tag of almost $3 million.³

REFERENCES

1. CRISPR Therapeutics announces FDA regenerative medicine advanced therapy (RMAT) designation granted to CTX130™ for the treatment of cutaneous t-cell lymphomas (CTCL). News release. CRISPR Therapeutics https://finance.yahoo.com/news/crispr-therapeutics-announces-fda-regenerative-120000758.html. September 28, 2022.
2. Vertex and CRISPR Therapeutics Announce Global exa-cel Regulatory Submissions for Sickle Cell Disease and Beta Thalassemia in 2022. News release. Vertex Pharmaceuticals. September 27, 2022. https://investors.vrtx.com/news-releases/news-release-details/vertex-and-crispr-therapeutics-announce-global-exa-cel
3. FDA approves first cell-based gene therapy to treat adult and pediatric patients with beta-thalassemia who require regular blood transfusions. News release. FDA. August 17, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cell-based-gene-therapy-treat-adult-and-pediatric-patients-beta-thalassemia-who?utm_medium=email&utm_source=govdelivery