Sickle cell anemia (SCD) is a global health concern, particularly prevalent in populations with African, Middle Eastern, Mediterranean, and South Asian ancestry. As per DelveInsight, there are nearly 123,300 prevalent cases of SCD in the United States. Bone marrow transplantation, or hematopoietic stem cell transplantation (HSCT), remains the only established cure for sickle cell disorder (SCD). However, ongoing research and development efforts are exploring new treatments and potential cures. Gene therapy and gene editing techniques show significant promise in correcting the genetic mutation that causes SCD. Notably, two innovative CRISPR-based therapies, CASGEVY (Exa-cel) and LYFGENIA (Lovo-cel), received approval in December 2023. 

One promising gene-edited therapy in the pipeline being explored for treating SCD is Renizgamglogene autogedtemcel (reni-cel/EDIT-301). This treatment involves modifying a patient's CD34+ hematopoietic stem and progenitor cells using a CRISPR/Cas12a ribonucleoprotein (RNP). The drug has also received ODD by the FDA, recently in April 2023, to treat SCD.

During the EHA 2024 conference, interim clinical data on the safety and efficacy of reni-cel from the ongoing RUBY trial (NCT04853576) were unveiled, highlighting its potential in treating patients with severe SCD.  Reni-cel has shown encouraging results for gene editing the y-globin gene (HBG1 and HBG2) promoters to induce HbF expression in SCD patients, marking the first clinical use of AsCas12a. Robust and clinically meaningful improvements were observed after treatment with reni-cel.

• Post-infusion, all patients remained free of vaso-occlusive events (VOE) with follow-up ranging from 2.4 to 22.8 months. 

• Across patients with ≥6 months follow-up, at month 6, the mean (standard deviation; SD) total Hb was 14.3 g/dL (2.1 g/dL) (n=9) with a mean (SD) HbF of 48.5% (3.7%) (n=10).

• The mean percentage of F-cells increased early and were sustained at >90% from month 4 through subsequent follow-ups for all patients with ≥4 months follow-up (n=12).

• There was also a trend towards improvement or normalization of hemolysis markers. 

Data from treated patients indicated early engraftment and a safety profile consistent with myeloablative busulfan conditioning and autologous HSCT. After reni-cel infusion, all patients (N=18) demonstrated successful neutrophil and platelet engraftment. Any Grade 3 or 4 Treatment emergent adverse events (TEAE) were observed in 94.4% (n = 17/18) of patients, and these events were not related to Reni-cel.

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KOL insights

“These new and promising data with a larger patient cohort support our belief that reni-cel can be a clinically differentiated, one-time, durable medicine that can provide life-changing clinical benefits to patients with sickle cell disease and beta thalassemia, specifically driving early and robust correction of anemia and sustained increases in fetal hemoglobin,” – MD, United States.

Conclusion 

In the SCD market, there is already intense competition owing to the several approvals that have been granted or are pending. An important step forward for SCD patients may be reached with the FDA's approval of CASGEVY and LYFGENIA in December 2023, which might provide a transformational treatment for those who are eligible. 

Reni-cel delivers patient-derived CD34+ hematopoietic stem and progenitor cells that are altered at the gamma globin gene promoters to upregulate the gamma globin, as opposed to suppressing the expression of the repressor gene BCL11A. This increases the fetal hemoglobin that normally occurs. Reni-cel can be a differentiated treatment option based on its robustness of the total hemoglobin levels and the cure of anemia. 

Data from the RUBY trial for Reni-cel showed that the treatment resulted in successful integration of the gene-edited cells, rapid and consistent normalization of hemoglobin levels, early improvements in fetal hemoglobin and F-cell percentages, enhancements in critical indicators of red blood cell breakdown, and a positive safety profile. The treatment showed effective gene editing of the HBG1/2 promoters to induce HbF expression, marking the first clinical use of AsCas12a. These encouraging findings from a larger patient cohort support further investigation of reni-cel in the RUBY trial.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to Sickle Cell Disease Market Insight, Epidemiology And Market Forecast 2034 report.

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