RuiFeng Bio Announces World’s First Successful Clinical Application of Novel HBG-Targeted Gene Editing Therapy for β-Thalassemia

Recently, Ruifeng Bio, an innovative gene-editing drug company, has achieved remarkable progress in the development of therapies for β-thalassemia. In a recent investigator-initiated clinical study conducted in collaboration with researchers, the first two patients to complete treatment have been successfully discharged.Globally, this marks the first successful report of a gene-editing therapy targeting a novel locus for the treatment of severe β-thalassemia, representing a breakthrough clinical achievement in China’s gene-editing technology.

Thalassemia is the most widely distributed monogenic disorder globally, affecting the largest patient population. In China alone, there are over 30 million carriers, predominantly concentrated in South China. Previously, several companies worldwide, including those in Europe, the United States, and China, have announced clinical data and results for gene editing therapies targeting transfusion-dependent thalassemia. Among these, CTX001 from CRISPR Therapeutics, the most advanced candidate, is currently in Phase I/II clinical trials. These studies have all targeted the BCL11A gene, which regulates HbF expression. RayWind Bio has developed a novel precision editing drug targeting HBG1/2. Clinical data from enrolled subjects in its trials are significantly superior to those reported in other studies, including public data from CRISPR Therapeutics. The product possesses both first-in-class and best-in-class attributes.

Repharm and Editas Medicine (with gene-editing scientist Feng Zhang as its scientific founder) are representative biotechnology companies developing therapeutics targeting the novel HBG gene. In January 2022, Editas announced that its HBG-targeting gene-editing therapy for beta-thalassemia, EDIT-301, had received FDA approval for its Investigational New Drug (IND) application, marking the world’s first clinical trial authorization for a thalassemia therapy targeting HBG. Non-clinical studies and academic reports indicate that the HBG target offers superior potential drug safety, without interfering with the normal differentiation and development of hematopoietic stem cells. Compared with the progress made by U.S. companies, Repharm has completed the first global case of dosing and follow-up in a clinical study of an HBG-targeting therapy for thalassemia, demonstrating its international competitiveness in drug innovation and development speed.

Clinical study data demonstrate the product’s leading advantages in efficacy and safety. Two patients with transfusion-dependent thalassemia, aged 9.8 and 13.7 years respectively, both carried the most severe β0/β0 genotype. Following treatment, they achieved transfusion independence (hemoglobin concentration >90 g/L) on days 28 and 40 post-transplantation, respectively, and their platelet counts exceeded 100×10⁹/L on days 28 and 34 post-transplantation, respectively. Rapid reconstitution of the erythroid and megakaryocytic lineages was observed after cell infusion, with no treatment-related serious adverse events reported; notably, neither patient required care in a laminar airflow room. Comparative analysis indicates that these outcomes surpass those of similar products from domestic and international companies, including CRISPR Therapeutics. The patients have been discharged, with stable recovery of hematopoietic and immune function, and will continue to undergo follow-up.

Professor Fang Jianpei from Sun Yat-sen Memorial Hospital, Sun Yat-sen University, who serves as the Deputy Chairman of the National Health Commission’s Expert Committee on Pediatric Hematologic Diseases, is a renowned expert with extensive experience in the clinical treatment of thalassemia. He spoke highly of this achievement:“In China, the population with transfusion-dependent thalassemia is predominantly composed of children and adolescents, affecting a large number of families. The vast majority of these patients can only survive by relying on regular blood transfusions. Gene editing therapy will undoubtedly change the fate of these patients and their entire families. I am delighted to witness this breakthrough progress: it enables patients to become transfusion-independent rapidly, significantly reduces the need for red blood cell and platelet transfusions during the transplantation process, and lowers medical costs as well as the incidence of other complications for patients. It is hoped that the drug will be launched on the market as soon as possible, which would be a tremendous blessing for the patient community.”

The industrialization of gene-editing drugs in China is still in its early stages, with several first-tier companies gradually establishing their own distinct development profiles. RayWind Bio’s team is among the earliest internationally to advance the clinical translation of gene editing. Its Chief Scientist, Professor Huang Junjiu, was named one of “Nature’s 10” people who mattered in science in 2015 by the prestigious journal Nature. He pioneered scientific exploration of gene editing for thalassemia on the international stage and took the lead in researching a perfect repair strategy using single-base editing to correct point mutations associated with thalassemia. Currently, RayWind Bio is innovating in both ex vivo and in vivo curative gene-editing therapies to help more patients with genetic disorders and prevalent diseases achieve radical cures. Meanwhile, the company is undertaking original development of foundational gene-editing tools, including proprietary Cas editors and base editors with independent intellectual property rights.

As a breakthrough discovery in 21st-century life sciences, gene editing has become a platform technology for biomedical applications. Represented by CRISPR/Cas, it is revolutionizing drug modalities, with clinical applications gradually expanding from genetic disorders to high-prevalence diseases. Boasting promising industrial prospects, its pioneering application in the world’s largest population of patients with thalassemia—the most common monogenic genetic disorder—demonstrates that this novel technology will make significant social contributions to global healthcare. China’s development in this industry is highly anticipated.

Thalassemia is the most widely distributed and prevalent monogenic inherited disorder globally, and it is also the genetic disease with the greatest impact and highest incidence in China. The 2015 "Blue Book on Thalassemia in China" reported that there are approximately 30 million thalassemia gene carriers and 300,000 patients with transfusion-dependent thalassemia in China, with cases concentrated mainly in South China. In normal adult blood, the majority of hemoglobin molecules are HbA (α2β2), along with ≤2.5% HbA2 (α2δ2) and <2% HbF (γ2β2, fetal hemoglobin). Thalassemia results from an imbalance in hemoglobin synthesis due to reduced production of at least one globin polypeptide chain (β, α, γ, or δ), leading to red blood cell defects and functional abnormalities. Among these, transfusion-dependent β-thalassemia, which presents with the most severe clinical symptoms, is caused by mutations or deletions in the β-globin gene, resulting in partial loss (β+ allele) or complete loss (β0 allele) of β-globin function.

Allogeneic hematopoietic stem cell transplantation is currently the only curative treatment for transfusion-dependent β-thalassemia; however, this procedure is associated with high costs and significant risks. In the absence of hematopoietic stem cell transplantation, patients must rely on long-term blood transfusions and iron chelation therapy to sustain life. Ultimately, patients may die from organ failure caused by chronic iron overload.