In the first study, researchers used CRISPR/Cas9 to treat two inherited blood disorders, beta thalassemia and sickle cell disease (SCD). The trial, which demonstrated remarkable improvements in all participants, is the first time this revolutionary approach has been used successfully in these patient populations.

Given that the only FDA-approved cure for sickle cell disease, a bone marrow transplant, is not widely accessible, having another curative option would be life-changing for a large number of the sickle cell disease population, said press briefing moderator, Dr Catherine Bollard, of Childrens National Research Institute and George Washington University. While longer follow-up data are needed, this study is extremely exciting for the field.

Investigators reported interim safety and efficacy data from 10 patients who received an investigational gene-editing based therapy, CTX001. The trials are the first to test a CRISPR-Cas9 gene editing therapy in humans for a genetic disease, the researchers reported.

Sickle cell disease (SCD) can cause a variety of health problems including episodes of severe pain, called vaso-occlusive crises, as well as organ damage and strokes, while patients with transfusion-dependent thalassemia (TDT) are dependent on blood transfusions from early childhood.The only available cure for both diseases is a bone marrow transplant from a closely related donor, an option that is not available for the vast majority of patients because of difficulty locating matched donors, the cost, and the risk of complications.

In the studies, the researchers goal is to functionally cure the blood disorders using CRISPR/Cas9 gene-editing by increasing the production of fetal hemoglobin, which produces normal, healthy red blood cells as opposed to the misshapen cells produced by faulty hemoglobin in the bodies of individuals with the disorders.

The clinical trials involve collecting stem cells from the patients. Researchers edit the stem cells using CRISPR-Cas9 and infuse the gene-modified cells into the patients. Patients remain in the hospital for approximately one month following the infusion.

Prior to receiving their modified cells, the seven patients with beta thalassemia required blood transfusions around every three to four weeks and the three patients with SCD suffered episodes of severe pain roughly every other month.

All the individuals with beta thalassemia have been transfusion independent since receiving the treatment, a period ranging between two and 18 months. Similarly, none of the individuals with SCD have experienced vaso-occlusive crises since CTX001 infusion.

All patients showed a substantial and sustained increase in the production of fetal hemoglobin.

Researchers report that the safety of CTX001 infusion was generally consistent with the chemotherapy regimen received prior to cell infusion.

Four serious adverse events (SAEs) related or possibly related to CTX001 were reported in one patient with TDT: headache, haemophagocytic lymphohistiocytosis (HLH), acute respiratory distress syndrome, and idiopathic pneumonia syndrome. All four of these SAEs occurred in the context of HLH and were either resolved or clinically improving at the time of this analysis. No other CTX001-related SAEs were reported in the other patients with TDT or in any patients with SCD, said the investigators.

Haydar Frangoul, MD, Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute, HCA Healthcares TriStar Centennial Medical Center, said:What we have been able to do through this study is a tremendous achievement. By gene editing the patients own stem cells we may have the potential to make this therapy an option for many patients facing these blood diseases.

Because of the precise way CRISPR-Cas9 gene editing works, Dr Frangoul suggested the technique could potentially cure or ameliorate a variety of diseases that have genetic origins.

The trial was sponsored by CRISPR Therapeutics and Vertex Pharmaceuticals.

The second two studies indicate new opportunities to reach a broader patient population with chimeric antigen receptor T-cell (CAR-T) therapy, which has been shown to be effective in some blood cancers but does not work in all patients.

One of the new studies offers an explanation as to why some patients do not respond to CD19-CAR-T therapy and suggests a way to overcome this resistance. The other study suggests CD19-CAR-T may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments.

Getting more data on CD19-CAR-T therapy in the high-risk non-Hodgkin lymphoma population is very important, said Dr Bollard. We know that CD19-CAR-T therapy does not work for some patients, so these studies underscore the need to better understand the immune evasion mechanisms T cells might be susceptible to and not just focus on their role as a vehicle for the CAR. Doing so may improve our capacity to administer effective T-cell immunotherapies.

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ASH virtual event hears about CRISPR and CAR-T based approaches to hard-to-treat blood disorders and cancers - BioPharma-Reporter.com