Five Notable CGT Therapy Trial Terminations in 2025: Setbacks Amid Innovation

In the field of cell and gene therapy (CGT), while innovative explorations continue to advance, numerous challenges are also being faced, leading to the termination of some trials for various reasons. From January 2025 to the present, several high-profile trials in this area have been terminated. Below is a detailed summary for you.

1. Cargo Therapeutics Terminates Phase II Study of Firi-cel for Large B-Cell Lymphoma

On January 29, 2025, Cargo Therapeutics announced that it would terminate the FIRCE-1 Phase II study of its experimental CAR-T therapy firi-cel for patients with large B-cell lymphoma (LBCL).

FIRI-CEL IS A CAR-T THERAPY TARGETING THE CD22 PROTEIN ON B CELLS. IN THE FIRCE-1 STUDY, A TOTAL OF 51 PATIENTS WERE ENROLLED. ALTHOUGH THE OVERALL RESPONSE RATE AND COMPLETE RESPONSE RATE WERE 77% AND 43%, RESPECTIVELY, THE TREATMENT RESPONSE WAS NOT DURABLE. AT THREE MONTHS, THE DURABILITY OF COMPLETE RESPONSE WAS ONLY 18%. ADDITIONALLY, 18% OF PATIENTS DEVELOPED TOXICITY ASSOCIATED WITH CAR-T THERAPY, NAMELY IMMUNE EFFECTOR CELL-ASSOCIATED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS-LIKE SYNDROME, INCLUDING AT LEAST ONE CASE THAT RESULTED IN PATIENT DEATH. BASED ON THE LACK OF A COMPETITIVE BENEFIT-RISK RATIO FOR PATIENTS, CARGO THERAPEUTICS MADE THE DECISION TO TERMINATE THE STUDY.

Following the news, shares of Cargo Therapeutics fell over 70%. Concurrently, Cargo Therapeutics announced a workforce reduction of approximately 50% to extend its cash runway and prioritize advancing its trispecific CAR-T therapy, CRG-023, to Phase 1 proof-of-concept data. The therapy targets CD19/CD20/CD22, with a Phase 1 dose-escalation study planned to commence in the second quarter of 2025. The company is also developing an allogeneic program that remains in preclinical studies.

2. AlloVir Terminates Three Phase 3 Clinical Trials of Core Product Posoleucel

In early January, AlloVir announced the termination of three Phase 3 clinical trials for its core product, Posoleucel. Posoleucel is an experimental multivirus-specific T-cell therapy. The three clinical trials halted by AlloVir involve prevention of infections or diseases caused by multiple viruses, treatment of virus-associated hemorrhagic cystitis (vHC), and treatment of adenovirus (AdV).

3. Pfizer Terminates Collaboration with Sangamo on Gene Therapy for Hemophilia A

On December 30, Pfizer announced the termination of its collaboration with Sangamo Therapeutics on the gene therapy giroctocogene fitelparvovec (giro-vec) for hemophilia A. Despite positive results from the Phase III trial and an upcoming regulatory submission, Pfizer, after comprehensive analysis, determined that patient interest in additional gene therapy options is currently very limited. The collaboration will conclude on April 21, 2025, just before the planned submissions for this gene therapy in the U.S. and European markets, which were originally scheduled for early 2025.

Sangamo CEO Says Pfizer's Termination of Partnership at Submission Eve Came as a Surprise and Deep Disappointment. The AFFINE trial had shown that, in adults with moderate to severe Hemophilia A, giro-vec significantly reduced the annualized total bleeding rate compared to routine Factor VIII prophylaxis.

4. Roche Terminates Clinical Development of SPK-3006 Gene Therapy

SPK-3006, a liver-targeted AAV investigational gene therapy developed by Spark Therapeutics, a Roche subsidiary, for the treatment of Pompe disease, has been removed from Roche’s pipeline review in the first half of 2024. The decision to halt clinical development was not due to safety concerns but was made as part of a strategic prioritization within Spark's internal portfolio.

5. Turnstone Biologics Terminates TIDAL-01 Development

In early February, Turnstone Biologics announced the termination of the development of its only clinical-stage TIL pipeline, TIDAL-01. This star biotech, which had raised over $220 million and undergone two transformations, ultimately fell on the eve of TIL's dawn. Originally known for its oncolytic virus technology, Turnstone shifted to TIL therapy due to unsatisfactory progress. Phase I data of TIDAL-01 in treating colorectal cancer had shown some positive effects: among four evaluable patients, the overall response rate (ORR) was 25%, and the disease control rate (DCR) was 50%, with one patient showing durable complete response (CR). However, due to the need for continuous investment in process improvements for Selected TIL production, and after considering funding requirements and the current financial market, the company decided to halt the development.

The termination of these trials reflects the complex challenges faced by the CGT field in the R&D process, including efficacy, safety, funding, market demand, and more. Despite setbacks, advancements and innovations in technology are expected to bring more successful therapies in the future, offering hope to patients.

Reference: Public Reports