The field of therapeutic gene editing has rapidly evolved from experimental promise to clinical reality, with CRISPR Medicine News monitoring approximately 250 clinical trials involving gene-editing therapeutic candidates as of February 2025. More than 150 trials are currently active, spanning multiple therapeutic areas and representing a diverse array of editing technologies including CRISPR-Cas, base editors, prime editors, zinc fingers, TALENs, meganucleases, CAS-CLOVER, RNA editors, and epigenetic-editing technology.
Breakthrough Approval Marks New Era
The clinical landscape achieved a historic milestone in 2023 when CASGEVY became the first approved CRISPR-based therapy, receiving regulatory clearance in multiple regions for the treatment of sickle cell disease and beta thalassemia. This achievement marked the transition of therapeutic gene editing from promise to reality.
CASGEVY received approval from the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) in November 2023, followed by FDA approval for sickle cell disease in December 2023, and European Medicines Agency (EMA) approval in February 2024. According to the FDA, it represents the first FDA-approved treatment to employ a novel genome editing technology, marking a groundbreaking advancement in gene therapy.
Clinical Trial Results Demonstrate Efficacy
The CASGEVY clinical trials showed remarkable results across both conditions. In the sickle cell disease trial, 29 out of 45 participants were followed long enough to announce reliable results, with 28 of these patients no longer suffering from vaso-occlusive crises characteristic of the disease at least one year following treatment.
For beta thalassemia, out of 54 people who received the treatment, 42 participated for sufficient duration to draw reliable conclusions. Among these patients, transfusions were unnecessary for at least one year for 39 individuals, while three patients experienced a 70% reduction in transfusion requirement.
Expanding Therapeutic Landscape
The clinical applications now encompass 15 diverse therapeutic areas:
- Blood cancers
- Haemoglobinopathies
- Solid cancers
- Viral diseases
- Metabolic disorders
- Autoimmune diseases
- Hereditary amyloidosis
- Inherited eye diseases
- Cardiovascular disease
- Bacterial diseases
- Immunodeficiencies
- Haemophilia
- Neurological conditions
- Muscular dystrophy
- Other rare inherited diseases
Blood Disorders Lead Clinical Development
Gene editing for blood disorders continues to lead the field, with the majority of Phase 3 trials targeting sickle cell disease and/or beta thalassemia. Phase 3 trials are also underway in hereditary amyloidosis and immunodeficiencies, demonstrating the expanding scope of advanced-stage clinical development.
Next-Generation Approaches Show Promise
Beyond CASGEVY, several next-generation approaches are advancing through clinical trials. Editas Medicine is conducting phase 1/2 trials for individuals with severe sickle cell disease (RUBY trial) and transfusion-dependent beta thalassemia (EdiTHAL trial), employing a CRISPR system featuring AsCas12a protein (EDIT-301). As of October 2024, the company announced that 28 patients received the drug in the RUBY trial, which was well tolerated at a median of 9.5 months follow-up.
Beam Therapeutics initiated their phase 1/2 trial (BEACON) for base editing therapy targeting severe sickle cell disease, with their therapeutic BEAM-101 involving precise, single-letter changes that exclude double-strand DNA cuts. Clinical data from 7 patients presented at the 66th American Society of Hematology Annual Meeting showed greater than 60% foetal haemoglobin induction and less than 40% Haemoglobin S reduction along with resolution of anaemia in all patients.
CAR-T Cell Therapy Advances
CRISPR technology is also revolutionizing CAR-T cell therapy development. CRISPR Therapeutics is investigating allogeneic CRISPR-modified CAR-T cell variants, with their products CTX110 and CTX130 showing favourable results in B- and T-cell lymphoma and renal cell carcinoma trials.
Caribou Biosciences achieved remarkable outcomes targeting CD19 in challenging B-cell non-Hodgkin lymphomas, incorporating a genetic alteration that deactivates the programmed death-1 (PD-1) gene. As of July 2023, their product CB-010 demonstrated a 94% overall response rate in the ANTLER Phase 1 clinical trial, with 69% of patients displaying complete response.
In Vivo Applications Expand
The field has expanded beyond ex vivo editing to include in vivo applications. Intellia Therapeutics' NTLA-2001 represents the first investigative CRISPR therapy candidate designed for systemic administration, targeting transthyretin amyloidosis through intravenous delivery. Clinical data from 27 participants showed substantial reduction (greater than 85%) in toxic protein levels even at the lowest treatment dosage, with the highest dose achieving reduction exceeding 90%.
Future Outlook
The clinical register is routinely updated to reflect new developments in the field, with gene editing technologies continuing to advance across multiple therapeutic areas. The success of CASGEVY has paved the way for numerous other CRISPR-based therapies currently in development, representing a new era of precision medicine with the potential to address previously untreatable genetic conditions.
As the field continues to mature, the focus remains on expanding the therapeutic applications while ensuring safety and efficacy across diverse patient populations and disease conditions.
