Gene-editing therapy frees first trial participant from SCD symptoms
Small study in China still recruiting patients for clinical testing of CS-206
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A patient with severe sickle cell disease (SCD) remained free of two key SCD symptoms — including painful vaso-occlusive crises — for more than a year after receiving a single dose of CS-206, Correctsequence Therapeutics‘ investigational gene-editing therapy, new data show.
The woman represents the first patient treated with CS-206 in a China-based Phase 1 clinical trial (NCT06565026), which is still recruiting an estimated five people with the inherited blood disorder, the company announced in a press release. According to the developer, the woman has shown no signs of anemia, marked by low red blood cell counts, nor experienced vaso-occlusive crises, known as VOCs, since receiving treatment.
The trial, now enrolling patients ages 12-35, is testing the therapy candidate at the First Affiliated Hospital of Guangxi Medical University.
“The follow-up data demonstrated favorable safety and efficacy of CS-206,” the developer stated, noting that “the patient has remained free from VOCs and anemia for 13 consecutive months, achieving the [trial’s] primary efficacy endpoint.”
SCD is marked by an abnormal form of hemoglobin, the oxygen-carrying protein in red blood cells. As a result, red blood cells adopt a rigid, sickle-like shape rather than the normal, flexible disc shape.
These misshapen cells break apart more easily, driving chronic anemia. They can also become trapped in small blood vessels, blocking blood flow and depriving tissues of oxygen, which can trigger VOCs.
CS-206 uses pencil-like tool for ‘safer’ gene editing
Similar to the SCD-approved gene-editing therapy Casgevy (exagamglogene autotemcel), CS-206 reactivates fetal hemoglobin, called HbF. This version of hemoglobin is produced during fetal development but is replaced soon after birth by its adult form.
Casgevy has proven highly effective at curing SCD. The therapy, however, uses the CRISPR-Cas9 gene-editing tool, which cuts both DNA strands like a pair of scissors. This can potentially increase the risk of unwanted genetic deletions and mutations in nontarget DNA regions.
To address these potential risks, Correctseq’s scientific cofounders created the transformer Base Editing (tBE) tool, which acts like a pencil, changing a single nucleotide — or building block of DNA — without cutting the DNA strand. According to the company, this is a “safer and more efficient therapeutic approach.”
CS-206 uses tBE to introduce genetic changes that mimic hereditary persistence of fetal hemoglobin (HPFH), a benign condition characterized by the ongoing production of HbF beyond infancy. By boosting fetal hemoglobin’s production, more healthy hemoglobin is generated, thereby preventing red blood cell sickling and easing SCD symptoms.
The treatment involves collecting a patient’s own hematopoietic stem cells, bone marrow cells that give rise to all blood cells. After cells are genetically modified in the lab, they are returned to the patient, where they are expected to restore healthy blood cell production.
Before the infusion, patients must also undergo a round of high-dose chemotherapy to destroy unhealthy cells and make room for the new edited cells.
Tech underlying CS-206 first used for another blood disease
Correctseq’s tBE technology has been first tested in beta-thalassemia, another hemoglobin disorder. That first HbF-boosting gene-editing candidate, called CS-101, has been used to treat more than 10 people with beta-thalassemia in China, Laos, Malaysia, and Pakistan. All patients have remained blood transfusion-free for more than 15 months, with the longest duration exceeding 30 months, or 2.5 years, data show.
The first participant in the CS-206 Phase 1 study was a 21-year-old woman with SCD from Nigeria who had experienced recurrent severe VOCs before treatment. After CS-206, she achieved what was described as “rapid and efficient hematopoietic reconstitution,” meaning her body successfully rebuilt a healthy blood cell-producing system.
By day 13, she showed neutrophil engraftment, or the recovery of blood immune cells that fight infection, and by day 21, an increase in platelets, the cell fragments in blood that help blood clot, the company stated.
Within one month, blood levels of HbF increased significantly, while levels of faulty hemoglobin (HbS) declined. By month three, the HbF-to-HbS ratio stabilized and was maintained thereafter, per the developer.
Starting from 60 days after her last red blood cell transfusion, the woman has been free of both VOCs and anemia for more than a year, meeting the trial’s primary efficacy goal. No treatment-related adverse events have been observed to date, per the company.
