CRISPR gene editing technology that won scientists Jennifer Doudna and Emmanuelle Charpentier the 2020 Nobel Prize in chemistry appear to be precipitating into the prescription pad. In the just concluded conference at the 2022 European Hematology Association Congress in Switzerland, Vertex Pharmaceuticals and CRISPR Therapeutics presented new data with longer follow-up for patients treated with the novel drug Exa-cel.
Exa-cel, which is short for exagamglogene autotemcel, would be the first gene editing drug designed to treat the blood disorders: sickle cell disease (SCD) and beta-thalassemia BT.
SCD affects approximately 100,000 Americans. It is a blood disorder in which the red blood cells are misshapen and can block blood vessels, leading to severe and sometimes life-threatening vaso-occlusive crises. Beta thalassemia is an inherited blood disorder in which the body produces less hemoglobin than normal. This disorder is rare in the United States, affecting approximately 1 in 100,000 individuals in the general population. However, it is a very common hereditary disorder in other parts of the world.
Vertex and CRISPR therapy involve harvesting stem cells from a patient. After extraction, the patient’s DNA is modified by Exa-cel to reactivate a form of hemoglobin the body only produces in infancy. The modified cells are then put back inside the body to boost the production of healthy blood cells in sickle cell and beta-thalassemia patients.
“By reactivating a naturally occurring developmental process, exa-cel restores fetal hemoglobin production and thereby can ameliorate the course of these diseases,” Haydar Frangoul, Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute, said in a press release “The remarkable results based on this approach give me great optimism and confidence in the potential of this treatment for patients.”
At the high-profile medical conference, the companies presented data from 75 patients who have been followed up for up to 37.2 months to demonstrate the effectiveness of exa-cel. 44 of these patients had transfusion-dependent beta-thalassemia (TDT), and 31 had severe sickle cell disease (SCD). According to the data presented, after 1.2 to 37.2 months after exa-cel infusion, 42 of the 44 patients with TDT were reported to be transfusion free. The remaining two patients who were not yet transfusion free also showed significant progress with 75% and 89% reductions in transfusion volume. They also reported a substantial increase in fetal hemoglobin (HbF) and mean total hemoglobin (Hb).
Of the patients with severe SCD, all 31 have had about 4 severe vaso-occlusive crises (VOCs) in the last two years before the start of the study. After excel infusion, all 31 patients were free of VOCs for the duration of the follow-up (2.0-32.3 months)
Regarding adverse effects, two patients among the 44 patients with TDT reported serious adverse effects related to excel treatment. One of the patients who has been reported in previous studies had a potentially life-threatening immune reaction. After treatment with Exa-cel, they later found out another patient had low circulating blood platelet and delayed neutrophil engraftment. However, according to the new report, both cases of serious adverse effects have been resolved. They also reported there were no cases of serious adverse effects in sickle cell patients.
“I have seen first-hand the impact that this investigational therapy has had on patients in these clinical trials and continue to be impressed by the totality of the data,” said Franco Locatelli, M.D., Ph.D., Professor of Pediatrics at the Sapienza University of Rome “Given the urgency for highly effective and curative therapies for patients with hemoglobinopathies, I am excited to be part of the team working towards the goal of addressing this unmet need.”
Vertex Pharmaceuticals and CRISPR Therapeutics also hope to ask for approval of the groundbreaking therapy in the U.S., U.K., and Europe before the end of the year.
Source: CRISPR press release