CRISPR Trial Update: Editas Reports Positive Initial Data From Sickle Cell Disease and Beta-Thalassemia Trials

On Friday last, Editas Medicine reported positive initial safety and efficacy data from the first four patients with sickle cell disease (SCD), and from the first transfusion-dependent beta thalassemia patient treated with EDIT-301, in the ongoing RUBY and EdiTHAL trial, respectively.

EDIT-301 is an autologous (i.e. patient-derived) CRISPR-edited cell therapy candidate, which is designed to be a one-time treatment for SCD and BT. It works by reactivating foetal haemoglobin (HbF) production, thereby compensating for the lack of functional adult haemoglobin in individuals with SCD and BT (see Fact Box).

A single dose of EDIT-301 leads to persistant improvements in haemoglobin levels with no serious adverse events

Editas reports that of the first four patients dosed in the RUBY trial, Patients 1 and 2 reached normal haemoglobin levels five months post-treatment with EDIT-301, and both patients have maintained a normal haemoglobin level at ten- and six-months follow-up, respectively. These patients have also seen foetal haemoglobin levels of greater than 40% persist during the same time frame. Patients 3 and 4 saw increases in total haemoglobin and foetal haemoglobin at three and two months follow-up, respectively, that follow similar patterns as those seen in Patients 1 and 2. All four treated RUBY patients are also free of vaso-occlusive events since infusion.

In the EdiTHAL trial, the first patient demonstrated successful neutrophil and platelet engraftment, and, at one and a half months post-infusion, the patient’s response was reported to resemble that of the first four RUBY patients.

In both trials, EDIT-301 was reportedly well-tolerated and demonstrated a safety profile consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant. The company reports that no serious adverse events occurred after EDIT-301 infusion, and that no adverse events reported were related to treatment with EDIT-301.

EDIT-301 is a CRISPR-Cas12a-edited cell therapy designed to reactivate foetal haemoglobin

Specifically, EDIT-301 is developed using a CRISPR-Cas12a ribonucleoprotein to enhance the HBG1/2 promoter region in the beta-globin locus of patient-derived haematopoietic stem cells (HPSCs). Naturally-occurring HbF-inducing mutations at the HBG1/2 region support the clinical relevance of using gene editing to enhance the HBG1/2 promoter, and this strategy has been shown to increase the red blood cell levels of HbF.

EDIT-301 was the first experimental medicine to be developed using CRISPR-Cas12a gene-editing technology, and dosing of the first patient in the RUBY trial in July 2022 marked the first time that Editas' engineered AsCas12a enzyme was used to edit human cells in a clinical trial.

In August 2020, Editas announced that it had obtained a Rare Pediatric Disease Designation for EDIT-301 as a potentially best-in-class treatment for SCD in children from birth to 18 years. The company obtained FDA clearance to initiate the RUBY trial in January 2022, and shared positive data from first two patients treated in the RUBY trial in December 2022.

We will provide further details on the RUBY and EdiTHAL trials as they emerge.

You can find all our previous news articles about IND approvals and clinical trials here. For a complete overview of CRISPR IND approvals and ongoing gene-editing trials, check out CRISPR Medicine News' Clinical Trials Database.