Risto-cel showing lasting benefits for people with severe SCD in trial
Developer shares new data on gene-edited cell therapy, formerly BEAM-101
Risto-cel, Beam Therapeutics‘ single-dose, gene-edited cell therapy candidate for people with severe sickle cell disease (SCD), continues to demonstrate sustained therapeutic benefits for as long as 20 months, or nearly two years.
That’s according to new data covering 31 adults and adolescents with SCD who received risto-cel, formerly BEAM-101, as part of the ongoing Phase 1/2 BEACON clinical trial (NCT05456880).
Among the improvements seen in these SCD patients were increases in protective fetal hemoglobin, lessening of anemia and other disease markers, and the prevention of severe vaso-occlusive crises (VOCs).
“The strength of these updated data from the BEACON trial reinforce the potential of risto-cel to deliver durable clinical benefit through efficient, more precise [gene] editing, and optimized cell collection and manufacturing processes,” John Evans, Beam’s CEO, said in a company press release. “Given the rapid clinical execution of the BEACON trial, we’re on track to efficiently dose the remaining patients enrolled in the study.”
The data were shared at the 67th American Society of Hematology Annual Meeting and Exposition, held Dec. 6-9 in Orlando, Florida, and virtually.
In SCD, genetic mutations result in the production of HbS, a defective form of adult hemoglobin, which is the protein that normally carries oxygen in red blood cells. HbS causes red blood cells to become rigid and sickle-shaped, thereby blocking small blood vessels and triggering painful VOCs. Sickled red blood cells also die prematurely, giving rise to anemia, marked by low numbers of these red blood cells in the body, and other SCD symptoms.
Risto-cel works to offset the harmful effects of HbS by reactivating the gene that codes for fetal hemoglobin (HbF) — a form of the protein produced before birth and then replaced by adult hemoglobin in the first months of life.
BEACON trial has been testing Risto-cell since 2022
The treatment involves collecting a patient’s hematopoietic stem cells, the cells that generate all types of blood cells, and genetically modifying them in the lab to increase HbF production.
The patient’s existing stem cells are eliminated using a conditioning regimen of the chemotherapy busulfan, and the modified cells are then infused back into the patient, where they’re expected to give rise to HbF-producing red blood cells.
Risto-cel has received orphan drug status and regenerative medicine advanced therapy designation from the U.S. Food and Drug Administration. These designations provide benefits and incentives meant to accelerate a therapy’s clinical development and regulatory review.
The multicenter, U.S.-based BEACON trial, which enrolled the first participant in 2022, is testing risto-cel in people ages 18-35 with severe SCD who had at least four VOCs in the two years before the study’s start.
No need for platelet transfusions after treatment for 29% of patients
The newly presented data concern the 31 treated patients to date, with follow-up data ranging from nine days to 20.4 months.
According to Beam, risto-cel’s efficient cell collection and manufacturing processes allowed patients to require few stem cell collection cycles. This was indicated by a median of one cycle over a median of three total collection days for the risto-cel manufacturing process and back-up cell collection.
Following treatment, participants showed rapid engraftment, or reconstitution of bone marrow, where hematopoietic stem cells give rise to new blood cells. Neutrophils, an immune cell, and platelets, which are cell fragments involved in blood clotting, took a median of two to three weeks to recover.
Severe neutropenia, indicated by low neutrophil counts, was reported for a median of seven days, and 29% of participants were able to avoid platelet transfusions after risto-cel.
“Given the cumbersome nature of the transplant process, it is encouraging that patients receiving risto-cel are on average experiencing a low number of cell collection cycles, rapid neutrophil and platelet [recovery], and low neutropenic days post-risto-cel treatment,” said Ashish Gupta, MD, a pediatric blood and marrow transplant physician and associate professor at the University of Minnesota. “Each of these factors contributes to fewer days in the hospital, potentially improving the overall patient experience.”
Gene-editing efficiency remained high and durable in peripheral blood and bone marrow after risto-cell treatment, with 67.4% of circulating red blood cells at six months and 72.8% at 12 months producing HbF, the company reported.
New data show no severe vaso-occlusive crisis after cell therapy
Importantly, according to Beam, no severe VOCs were reported after engraftment. HbF levels increased rapidly, with participants achieving mean levels higher than 60% and durable reductions in HbS below 40%. Mean per-cell HbF levels were maintained above the sickling threshold throughout follow-up.
These findings were consistent with data reported in June from the first 17 SCD patients dosed with risto-cel.
The therapy was also associated with rapid increases in total hemoglobin, resulting in complete resolution of anemia. Consistent reductions were observed across markers of red blood cell destruction and sickling parameters. Also, levels of erythropoietin, a hormone that stimulates red blood cell production, returned to normal, the data showed.
Risto-cel’s safety profile aligned with expectations for busulfan conditioning and stem cell transplants. Common adverse events included inflammation of the tissue lining the mouth or lips, neutropenia with fever, and reduced appetite.
One previously reported death due to respiratory failure was deemed likely related to busulfan conditioning, and not to risto-cel, the company noted.
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